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  • 201.
    Forsberg, Daniel
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Eklund, Anders
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Andersson, Mats
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Non-Rigid Volume Registration - A CUDA-based GPU Implementation of the Morphon2011Conference paper (Other academic)
    Abstract [en]

    Image registration is frequently used within the medical image domain and where methods with high performance are required. The need for high accuracy coupled with high speed is especially important for applications such as adaptive radiation therapy and image-guided surgery. During the last years, a number of significant projects have been introduced to make the computational power of GPUs available to a wider audience. The most well known project is the introduction of CUDA (Compute Unified Device Architecture). In this paper, we present a CUDA based GPU implementation of a non-rigid image registration algorithm, known as the Morphon, and compare it with a CPU implementation of the Morphon. The achieved speedup, in the range of 51-54x, is also compared with speedups reported from other non-rigid registration methods mplemented on the GPU. These include the Demons algorithm and a mutual information based algorithm.

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  • 202.
    Forsberg, Daniel
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Eklund, Anders
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Andersson, Mats
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Phase-Based Non-Rigid 3D Image Registration - From Minutes to Seconds Using CUDA2011Conference paper (Other academic)
    Abstract [en]

    Image registration is a well-known concept within the medical image domain and has been shown to be useful in a number of dierent tasks. However, due to sometimes long processing times, image registration is not fully utilized in clinical workows, where time is an important factor. During the last couple of years, a number of signicant projects have been introduced to make the computational power of GPUs available to a wider audience, where the most well known is CUDA. In this paper we present, with the aid of CUDA, a speedup in the range of 38-44x (from 29 minutes to 40 seconds) when implementing a phasebased non-rigid image registration algorithm, known as the Morphon, on a single GPU. The achieved speedup is in the same magnitude as the speedups reported from other non-rigid registration algorithms fully ported to the GPU. Given the impressive speedups, both reported in this paper and other papers, we therefore consider that it is now feasible to eectively integrate image registration into various clinical workows, where time is a critical factor.

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  • 203.
    Forsberg, Daniel
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Farnebäck, Gunnar
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, The Institute of Technology.
    Westin, Carl-Fredrik
    Harvard Medical School.
    Multi-modal Image Registration Using Polynomial Expansion and Mutual Information2012In: Biomedical Image Registration: Proceedings of the 5th International Workshop, WBIR 2012, Nashville, TN, USA, July 7-8, 2012 / [ed] Benoit M. Dawant, Gary E. Christensen, J.Michael Fitzpatrick and Daniel Rueckert, Springer Berlin/Heidelberg, 2012, p. 40-49Chapter in book (Refereed)
    Abstract [en]

    This book constitutes the refereed proceedings of the 5th International Workshop on Biomedical Image Registration, WBIR 2012, held in Nashville, Tennessee, USA, in July 2012. The 20 full papers and 11 poster papers included in this volume were carefully reviewed and selected from 44 submitted papers. They full papers are organized in the following topical sections: multiple image sets; brain; non-rigid anatomy; and frameworks and similarity measures.

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  • 204.
    Forsberg, Daniel
    et al.
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV). Sectra AB, Linköping, Sweden.
    Lindblom, Maria
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Quick, Petter
    Linköping University, Department of Medical and Health Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Gauffin, Håkan
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Quantitative analysis of the patellofemoral motion pattern using semi-automatic processing of 4D CT data2016In: International Journal of Computer Assisted Radiology and Surgery, ISSN 1861-6410, E-ISSN 1861-6429, Vol. 11, no 9, p. 1731-1741Article in journal (Refereed)
    Abstract [en]

    To present a semi-automatic method with minimal user interaction for quantitative analysis of the patellofemoral motion pattern. 4D CT data capturing the patellofemoral motion pattern of a continuous flexion and extension were collected for five patients prone to patellar luxation both pre- and post-surgically. For the proposed method, an observer would place landmarks in a single 3D volume, which then are automatically propagated to the other volumes in a time sequence. From the landmarks in each volume, the measures patellar displacement, patellar tilt and angle between femur and tibia were computed. Evaluation of the observer variability showed the proposed semi-automatic method to be favorable over a fully manual counterpart, with an observer variability of approximately 1.5 for the angle between femur and tibia, 1.5 mm for the patellar displacement, and 4.0-5.0 for the patellar tilt. The proposed method showed that surgery reduced the patellar displacement and tilt at maximum extension with approximately 10-15 mm and 15-20 for three patients but with less evident differences for two of the patients. A semi-automatic method suitable for quantification of the patellofemoral motion pattern as captured by 4D CT data has been presented. Its observer variability is on par with that of other methods but with the distinct advantage to support continuous motions during the image acquisition.

  • 205.
    Forsberg, Daniel
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Sectra, Linköping, Sweden .
    Lundström, Claes
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Sectra, Linköping, Sweden .
    Andersson, Mats
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eigenspine: Eigenvector Analysis of Spinal Deformities in Idiopathic Scoliosis2014In: Computational Methods and Clinical Applications for Spine Imaging: Proceedings of the Workshop held at the 16th International Conference on Medical Image Computing and Computer Assisted Intervention, September 22-26, 2013, Nagoya, Japan / [ed] Jianhua Yao,Tobias Klinder, Shuo Li, Springer, 2014, Vol. 17, p. 123-134Conference paper (Refereed)
    Abstract [en]

    In this paper, we propose the concept of eigenspine, a data analysis schemeuseful for quantifying the linear correlation between different measures relevant fordescribing spinal deformities associated with spinal diseases, such as idiopathic scoliosis.The proposed concept builds upon the use of principal component analysis(PCA) and canonical correlation analysis (CCA), where PCA is used to reduce thenumber of dimensions in the measurement space, thereby providing a regularizationof the measurements, and where CCA is used to determine the linear dependence betweenpair-wise combinations of the different measures. To demonstrate the usefulnessof the eigenspine concept, the measures describing position and rotation of thelumbar and the thoracic vertebrae of 22 patients suffering from idiopathic scoliosiswere analyzed. The analysis showed that the strongest linear relationship is foundbetween the anterior-posterior displacement and the sagittal rotation of the vertebrae,and that a somewhat weaker but still strong correlation is found between thelateral displacement and the frontal rotation of the vertebrae. These results are wellin-line with the general understanding of idiopathic scoliosis. Noteworthy though isthat the obtained results from the analysis further proposes axial vertebral rotationas a differentiating measure when characterizing idiopathic scoliosis. Apart fromanalyzing pair-wise linear correlations between different measures, the method isbelieved to be suitable for finding a maximally descriptive low-dimensional combinationof measures describing spinal deformities in idiopathic scoliosis.

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  • 206.
    Forsberg, Daniel
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Lundström, Claes
    Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Andersson, Mats
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Model-based registration for assessment of spinal deformities in idiopathic scoliosis2014In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 59, no 2, p. 311-326Article in journal (Refereed)
    Abstract [en]

    Detailed analysis of spinal deformity is important within orthopaedic healthcare, in particular for assessment of idiopathic scoliosis. This paper addresses this challenge by proposing an image analysis method, capable of providing a full three-dimensional spine characterization. The proposed method is based on the registration of a highly detailed spine model to image data from computed tomography. The registration process provides an accurate segmentation of each individual vertebra and the ability to derive various measures describing the spinal deformity. The derived measures are estimated from landmarks attached to the spine model and transferred to the patient data according to the registration result. Evaluation of the method provides an average point-to-surface error of 0.9 mm ± 0.9 (comparing segmentations), and an average target registration error of 2.3 mm ± 1.7 (comparing landmarks). Comparing automatic and manual measurements of axial vertebral rotation provides a mean absolute difference of 2.5° ± 1.8, which is on a par with other computerized methods for assessing axial vertebral rotation. A significant advantage of our method, compared to other computerized methods for rotational measurements, is that it does not rely on vertebral symmetry for computing the rotational measures. The proposed method is fully automatic and computationally efficient, only requiring three to four minutes to process an entire image volume covering vertebrae L5 to T1. Given the use of landmarks, the method can be readily adapted to estimate other measures describing a spinal deformity by changing the set of employed landmarks. In addition, the method has the potential to be utilized for accurate segmentations of the vertebrae in routine computed tomography examinations, given the relatively low point-to-surface error.

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    Model-based registration for assessment of spinal deformities in idiopathic scoliosis
  • 207.
    Forsberg, Daniel
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Lundström, Claes
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology. Linköping University, The Institute of Technology.
    Andersson, Mats
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Knutsson, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Model-Based Transfer Functions for Efficient Visualization of Medical Image Volumes2011In: Image Analysis: 17th Scandinavian Conference, SCIA 2011, Ystad, Sweden, May 2011. Proceedings, Springer Berlin/Heidelberg, 2011, Vol. 6688/2011, p. 592-603Conference paper (Refereed)
    Abstract [en]

    The visualization of images with a large dynamic range is a difficult task and this is especially the case for gray-level images. In radiology departments, this will force radiologists to review medical images several times, since the images need to be visualized with several different contrast windows (transfer functions) in order for the full information content of each image to be seen. Previously suggested methods for handling this situation include various approaches using histogram equalization and other methods for processing the image data. However, none of these utilize the underlying human anatomy in the images to control the visualization and the fact that different transfer functions are often only relevant for disjoint anatomical regions. In this paper, we propose a method for using model-based local transfer functions. It allows the reviewing radiologist to apply multiple transfer functions simultaneously to a medical image volume. This provides the radiologist with a tool for making the review process more efficient, by allowing him/her to review more of the information in a medical image volume with a single visualization. The transfer functions are automatically assigned to different anatomically relevant regions, based upon a model registered to the volume to be visualized. The transfer functions can be either pre-defined or interactively changed by the radiologist during the review process. All of this is achieved without adding any unfamiliar aspects to the radiologist’s normal work-flow, when reviewing medical image volumes.

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  • 208.
    Forsberg, Daniel
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Lundström, Claes
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology.
    Andersson, Mats
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Vavruch, Ludvig
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Tropp, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Clinical and Experimental Medicine, Orthopaedics. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Orthopaedics in Linköping.
    Knutsson, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, Faculty of Health Sciences.
    Fully automatic measurements of axial vertebral rotation for assessment of spinal deformity in idiopathic scoliosis2013In: Physics in Medicine and Biology, ISSN 0031-9155, E-ISSN 1361-6560, Vol. 58, no 6, p. 1775-1787Article in journal (Refereed)
    Abstract [en]

    Reliable measurements of spinal deformities in idiopathic scoliosis are vital, since they are used for assessing the degree of scoliosis, deciding upon treatment and monitoring the progression of the disease. However, commonly used two dimensional methods (e.g. the Cobb angle) do not fully capture the three dimensional deformity at hand in scoliosis, of which axial vertebral rotation (AVR) is considered to be of great importance. There are manual methods for measuring the AVR, but they are often time-consuming and related with a high intra- and inter-observer variability. In this paper, we present a fully automatic method for estimating the AVR in images from computed tomography. The proposed method is evaluated on four scoliotic patients with 17 vertebrae each and compared with manual measurements performed by three observers using the standard method by Aaro-Dahlborn. The comparison shows that the difference in measured AVR between automatic and manual measurements are on the same level as the inter-observer difference. This is further supported by a high intraclass correlation coefficient (0.971-0.979), obtained when comparing the automatic measurements with the manual measurements of each observer. Hence, the provided results and the computational performance, only requiring approximately 10 to 15 s for processing an entire volume, demonstrate the potential clinical value of the proposed method.

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  • 209.
    Forsberg, Daniel
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Sectra, Linköping, Sweden.
    Lundström, Claes
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Science and Technology, Media and Information Technology. Linköping University, The Institute of Technology. Sectra, Linköping, Sweden.
    Knutsson, Hans
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eigenspine: Computing the Correlation between Measures Describing Vertebral Pose for Patients with Adolescent Idiopathic Scoliosis2014In: Computerized Medical Imaging and Graphics, ISSN 0895-6111, E-ISSN 1879-0771, Vol. 38, no 7, p. 549-557Article in journal (Refereed)
    Abstract [en]

    This paper describes the concept of eigenspine, a concept applicable for determining the correlation between pair-wise combinationsof measures useful for describing the three-dimensional spinal deformities associated with adolescent idiopathic scoliosis. Theproposed data analysis scheme is based upon the use of principal component analysis (PCA) and canonical correlation analysis(CCA). PCA is employed to reduce the dimensionality of the data space, thereby providing a regularization of the measurements,and CCA is employed to determine the linear dependence between pair-wise combinations of different measures. The usefulness ofthe eigenspine concept is demonstrated by analyzing the position and the rotation of all lumbar and thoracic vertebrae as obtainedfrom 46 patients suffering from adolescent idiopathic scoliosis. The analysis showed that the strongest linear relationship is foundbetween the lateral displacement and the coronal rotation of the vertebrae, and that a somewhat weaker but still strong correlationis found between the coronal rotation and the axial rotation of the vertebrae. These results are well in-line with the generalunderstanding of idiopathic scoliosis. Noteworthy though is that the correlation between the anterior-posterior displacement and thesagittal rotation was not as strong as expected and that the obtained results further indicate the need for including the axial vertebralrotation as a measure when characterizing different types of idiopathic scoliosis. Apart from analyzing pair-wise correlationsbetween different measures, the method is believed to be suitable for finding a maximally descriptive low-dimensional combinationof measures describing spinal deformities in idiopathic scoliosis.

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  • 210.
    Forsberg, Daniel
    et al.
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Sectra Imtec, Linkoping, Sweden.
    Rathi, Yogesh
    Harvard Medical School, Boston, MA, USA.
    Bouix, Sylvain
    Harvard Medical School, Boston, MA, USA.
    Wassermann, Demian
    Harvard Medical School, Boston, MA, USA.
    Knutsson, Hans
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Westin, Carl-Fredrik
    Harvard Medical School, Boston, MA, USA.
    Improving Registration Using Multi-channel Diffeomorphic Demons Combined with Certainty Maps2011In: Multimodal Brain Image Analysis: First International Workshop, MBIA 2011, Held in Conjunction with MICCAI 2011, Toronto, Canada, September 18, 2011. Proceedings, Springer Berlin/Heidelberg, 2011, Vol. 7012/2011, p. 19-26Conference paper (Refereed)
    Abstract [en]

    The number of available imaging modalities increases both in clinical practice and in clinical studies. Even though data from multiple modalities might be available, image registration is typically only performed using data from a single modality. In this paper, we propose using certainty maps together with multi-channel diffeomorphic demons in order to improve both accuracy and robustness when performing image registration. The proposed method is evaluated using DTI data, multiple region overlap measures and a fiber bundle similarity metric.

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  • 211. Order onlineBuy this publication >>
    Forsgren, Mikael
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Radiation Physics. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    The Non-Invasive Liver Biopsy: Determining Hepatic Function in Diffuse and Focal LiverDisease2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The liver is one of the largest organs within the human body and it handles many vital tasks such as nutrient processing, toxin removal, and synthesis of important proteins. The number of people suffering from chronic liver disease is on the rise, likely due to the present ‘western’ lifestyle. As disease develops in the liver there are pathophysiological manifestations within the liver parenchyma that are both common and important to monitor. These manifestations include inflammation, fatty infiltration (steatosis), excessive scar tissue formation (fibrosis and cirrhosis), and iron loading. Importantly, as the disease progresses there is concurrent loss of liver function. Furthermore, postoperative liver function insufficiency is an important concern when planning surgical treatment of the liver, because it is associated with both morbidity and mortality. Liver function can also be hampered due to drug-induced injuries, an important aspect to consider in drug-development.

    Currently, an invasive liver needle biopsy is required to determine the aetiology and to stage or grade the pathophysiological manifestations. There are important limitations with the biopsy, which include, risk of serious complications, mortality, morbidity, inter- and intra-observer variability, sampling error, and sampling variability. Cleary, it would be beneficial to be able investigate the pathophysiological manifestations accurately, non-invasively, and on regional level.

    Current available laboratory liver function blood panels are typically insufficient and often only indicate damage at a late stage. Thus, it would be beneficial to have access to biomarkers that are both sensitive and responds to early changes in liver function in both clinical settings and for the pharmaceutical industry and regulatory agencies.

    The main aim of this thesis was to develop and evaluate methods that can be used for a ‘non-invasive liver biopsy’ using magnetic resonance (MR). We also aimed to develop sensitive methods for measure liver function based on gadoxetate-enhanced MR imaging (MRI).

    The presented work is primarily based on a prospective study on c. 100 patients suffering from chronic liver disease of varying aetiologies recruited due to elevated liver enzyme levels, without clear signs of decompensated cirrhosis. Our results show that the commonly used liver fat cut-off for diagnosing steatosis should be lowered from 5% to 3% when using MR proton-density fat fraction (PDFF). We also show that MR elastography (MRE) is superior in staging fibrosis.

    Finally we presented a framework for quantifying liver function based on gadoxetate-enhanced MRI. The method is based on clinical images and a clinical approved contrast agent (gadoxetate). The framework consists of; state-of the-art image reconstruction and correction methods, a mathematical model, and a precise model parametrization method. The model was developed and validated on healthy subjects. Thereafter the model was found applicable on the chronic liver disease cohort as well as validated using gadoxetate levels in biopsy samples and blood samples. The liver function parameters correlated with clinical markers for liver function and liver fibrosis (used as a surrogate marker for liver function).

    In summary, it should be possible to perform a non-invasive liver biopsy using: MRI-PDFF for liver fat and iron loading, MRE for liver fibrosis and possibly also inflammation, and measure liver function using the presented framework for analysing gadoxetate-enhanced MRI. With the exception of an MREtransducer no additional hardware is required on the MR scanner. The liver function method is likely to be useful both in a clinical setting and in pharmaceutical trials.

    List of papers
    1. Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
    Open this publication in new window or tab >>Separation of advanced from mild hepatic fibrosis by quantification of the hepatobiliary uptake of Gd-EOB-DTPA
    Show others...
    2013 (English)In: European Radiology, ISSN 0938-7994, E-ISSN 1432-1084, Vol. 23, no 1, p. 174-181Article in journal (Refereed) Published
    Abstract [en]

    Objectives

    To apply dynamic contrast-enhanced (DCE) MRI on patients presenting with elevated liver enzymes without clinical signs of hepatic decompensation in order to quantitatively compare the hepatocyte-specific uptake of Gd-EOB-DTPA with histopathological fibrosis stage.

    Methods

    A total of 38 patients were prospectively examined using 1.5-T MRI. Data were acquired from regions of interest in the liver and spleen by using time series of single-breath-hold symmetrically sampled two-point Dixon 3D images (non-enhanced, arterial and venous portal phase; 3, 10, 20 and 30 min) following a bolus injection of Gd-EOB-DTPA (0.025 mmol/kg). The signal intensity (SI) values were reconstructed using a phase-sensitive technique and normalised using multiscale adaptive normalising averaging (MANA). Liver-to-spleen contrast ratios (LSC_N) and the contrast uptake rate (KHep) were calculated. Liver biopsy was performed and classified according to the Batts and Ludwig system.

    Results

    Area under the receiver-operating characteristic curve (AUROC) values of 0.71, 0.80 and 0.78, respectively, were found for KHep, LSC_N10 and LSC_N20 with regard to severe versus mild fibrosis. Significant group differences were found for KHep (borderline), LSC_N10 and LSC_N20.

    Conclusions

    Liver fibrosis stage strongly influences the hepatocyte-specific uptake of Gd-EOB-DTPA. Potentially the normalisation technique and KHep will reduce patient and system bias, yielding a robust approach to non-invasive liver function determination.

    Place, publisher, year, edition, pages
    Springer, 2013
    Keywords
    Quantification, Gd-EOB-DTPA, Dynamic contrast-enhanced MRI, Pharmacokinetics, Liver
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-87242 (URN)10.1007/s00330-012-2583-2 (DOI)000312324500022 ()
    Projects
    NILB
    Note

    Funding Agencies|Swedish Research Council|VR/M 2007-2884|Medical Research Council of South-east Sweden|FORSS 12621|Linkoping University, Linkoping University Hospital Research Foundations||County Council of Ostergotland||

    Available from: 2013-01-14 Created: 2013-01-14 Last updated: 2019-06-14
    2. Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
    Open this publication in new window or tab >>Physiologically Realistic and Validated Mathematical Liver Model Revels Hepatobiliary Transfer Rates for Gd-EOB-DTPA Using Human DCE-MRI Data
    Show others...
    2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 4, p. 0095700-Article in journal (Refereed) Published
    Abstract [en]

    Objectives: Diffuse liver disease (DLD), such as non-alcoholic fatty liver disease (NASH) and cirrhosis, is a rapidly growing problem throughout the Westernized world. Magnetic resonance imaging (MRI), based on uptake of the hepatocyte-specific contrast agent (CA) Gd-EOB-DTPA, is a promising non-invasive approach for diagnosing DLD. However, to fully utilize the potential of such dynamic measurements for clinical or research purposes, more advanced methods for data analysis are required. Methods: A mathematical model that can be used for such data-analysis was developed. Data was obtained from healthy human subjects using a clinical protocol with high spatial resolution. The model is based on ordinary differential equations and goes beyond local diffusion modeling, taking into account the complete system accessible to the CA. Results: The presented model can describe the data accurately, which was confirmed using chi-square statistics. Furthermore, the model is minimal and identifiable, meaning that all parameters were determined with small degree of uncertainty. The model was also validated using independent data. Conclusions: We have developed a novel approach for determining previously undescribed physiological hepatic parameters in humans, associated with CA transport across the liver. The method has a potential for assessing regional liver function in clinical examinations of patients that are suffering of DLD and compromised hepatic function.

    Place, publisher, year, edition, pages
    Public Library of Science, 2014
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:liu:diva-106962 (URN)10.1371/journal.pone.0095700 (DOI)000335226500139 ()
    Available from: 2014-06-04 Created: 2014-06-02 Last updated: 2019-06-14
    3. Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
    Open this publication in new window or tab >>Using a 3% Proton Density Fat Fraction as a Cut-off Value Increases Sensitivity of Detection of Hepatic Steatosis, Based on Results from Histopathology Analysis
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    2017 (English)In: Gastroenterology, ISSN 0016-5085, E-ISSN 1528-0012, Vol. 153, no 1, p. 53-+Article in journal (Refereed) Published
    Abstract [en]

    It is possible to estimate hepatic triglyceride content by calculating the proton density fat fraction (PDFF), using proton magnetic resonance spectroscopy (less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS), instead of collecting and analyzing liver biopsies to detect steatosis. However, the current PDFF cut-off value (5%) used to define steatosis by magnetic resonance was derived from studies that did not use histopathology as the reference standard. We performed a prospective study to determine the accuracy of less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF in measurement of steatosis using histopathology analysis as the standard. We collected clinical, serologic, less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF, and liver biopsy data from 94 adult patients with increased levels of liver enzymes (6 months or more) referred to the Department of Gastroenterology and Hepatology at Linköping University Hospital in Sweden from 2007 through 2014. Steatosis was graded using the conventional histopathology method and fat content was quantified in biopsy samples using stereological point counts (SPCs). We correlated less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF findings with SPCs (r = 0.92; P less than.001). less thansuperscriptgreater than1less than/superscriptgreater thanH-MRS PDFF results correlated with histopathology results (ρ = 0.87; P less than.001), and SPCs correlated with histopathology results (ρ = 0.88; P less than.001). All 25 subjects with PDFF values of 5.0% or more had steatosis based on histopathology findings (100% specificity for PDFF). However, of 69 subjects with PDFF values below 5.0% (negative result), 22 were determined to have steatosis based on histopathology findings (53% sensitivity for PDFF). Reducing the PDFF cut-off value to 3.0% identified patients with steatosis with 100% specificity and 79% sensitivity; a PDFF cut-off value of 2.0% identified patients with steatosis with 94% specificity and 87% sensitivity. These findings might be used to improve non-invasive detection of steatosis.

    Place, publisher, year, edition, pages
    Elsevier, 2017
    National Category
    Gastroenterology and Hepatology
    Identifiers
    urn:nbn:se:liu:diva-136544 (URN)10.1053/j.gastro.2017.03.005 (DOI)000403918300022 ()
    Note

    Funding agencies: Swedish Research Council/Medicine and Health [VR/M 2007-2884, VR/M 2012-3199]; Swedish Research Council/Natural and Engineering Sciences [VR/NT 2014-6157]; Swedish Innovation Agency VINNOVA [2013-01314]; Region Ostergotland (ALF)

    Available from: 2017-04-19 Created: 2017-04-19 Last updated: 2019-09-25Bibliographically approved
    4. Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort
    Open this publication in new window or tab >>Model-inferred mechanisms of liver function from magnetic resonance imaging data: Validation and variation across a clinically relevant cohort
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    2019 (English)In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 15, no 6, article id e1007157Article in journal (Refereed) Published
    Abstract [en]

    Estimation of liver function is important to monitor progression of chronic liver disease (CLD). A promising method is magnetic resonance imaging (MRI) combined with gadoxetate, a liver-specific contrast agent. For this method, we have previously developed a model for an average healthy human. Herein, we extended this model, by combining it with a patient-specific non-linear mixed-effects modeling framework. We validated the model by recruiting 100 patients with CLD of varying severity and etiologies. The model explained all MRI data and adequately predicted both timepoints saved for validation and gadoxetate concentrations in both plasma and biopsies. The validated model provides a new and deeper look into how the mechanisms of liver function vary across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate. These mechanisms are shared across many liver functions and can now be estimated from standard clinical images.

    Author summary

    Being able to accurately and reliably estimate liver function is important when monitoring the progression of patients with liver disease, as well as when identifying drug-induced liver injury during drug development. A promising method for quantifying liver function is to use magnetic resonance imaging combined with gadoxetate. Gadoxetate is a liver-specific contrast agent, which is taken up by the hepatocytes and excreted into the bile. We have previously developed a mechanistic model for gadoxetate dynamics using averaged data from healthy volunteers. In this work, we extended our model with a non-linear mixed-effects modeling framework to give patient-specific estimates of the gadoxetate transport-rates. We validated the model by recruiting 100 patients with liver disease, covering a range of severity and etiologies. All patients underwent an MRI-examination and provided both blood and liver biopsies. Our validated model provides a new and deeper look into how the mechanisms of liver function varies across a wide variety of liver diseases. The basic mechanisms remain the same, but increasing fibrosis reduces uptake and increases excretion of gadoxetate.

    Place, publisher, year, edition, pages
    San Francisco, CA, United States: Public Library of Science, 2019
    National Category
    Pharmaceutical Sciences
    Identifiers
    urn:nbn:se:liu:diva-159165 (URN)10.1371/journal.pcbi.1007157 (DOI)000474703000068 ()31237870 (PubMedID)2-s2.0-85069296906 (Scopus ID)
    Note

    Funding Agencies|Swedish Research Council [2014-6157, 2007-2884]; Medical Research council of Southeast Sweden [12621]; Vinnova [2013-01314]; Linkoping University, CENIIT [15.09]; Swedish fund for research without animal experiments [Nytank2015]

    Available from: 2019-07-30 Created: 2019-07-30 Last updated: 2019-12-12Bibliographically approved
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    The Non-Invasive Liver Biopsy: Determining Hepatic Function in Diffuse and Focal LiverDisease
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  • 212.
    Forslund, Pontus
    Linköping University, Department of Mechanical Engineering.
    A Neural Network Based Brain-Computer Interface for Classification of Movement Related EEG2003Independent thesis Advanced level (degree of Master (One Year)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    A brain-computer interface, BCI, is a technical system that allows a person to control the external world without relying on muscle activity. This thesis presents an EEG based BCI designed for automatic classification of two dimensional hand movements. The long-term goal of the project is to build an intuitive communication system for operation by people with severe motor impairments. If successful, such system could for example be used by a paralyzed patient to control a word processor or a wheelchair.

    The developed BCI was tested in an offine pilot study. In response to an external cue, a test subject moved a joystick in one of four directions. During the movement, EEG was recorded from seven electrodes mounted on the subject's scalp. An autoregressive model was fitted to the data, and the extracted coefficients were used as input features to a neural network based classifier. The classifier was trained to recognize the direction of the movements. During the first half of the experiment, real physical movements were performed. In the second half, subjects were instructed just to imagine the hand moving the joystick, but to avoid any muscle activity.

    The results of the experiment indicate that the EEG signals do in fact contain extractable and classifiable information about the performed movements, during both physical and imagined movements.

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  • 213. Fraser, A.G.
    et al.
    Wilkenshoff, U.
    Janerot-Sjöberg, B.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Rosenhek, R.
    Payne, N.
    Brodin, L-A.
    Quantitative stress echocardiography using tissue Doppler for the diagnosis of coronary artery disease2000In: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597Article in journal (Refereed)
  • 214.
    Fredly, Siv
    et al.
    Department of Neonatal Intensive Care Unit, Oslo University hospital, Ullevål, Oslo Norway.
    Häggblad, Erik
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Kvernebo, Knut
    Faculty of Medicine, University of Oslo, Oslo, Norway.
    Fugelseth, Drude
    Department of Neonatal Intensive Care Unit, Oslo University hospital, Ullevål, Oslo Norway.
    Skin microcirculation in healthy newborns- assessments of morphology, perfusion and oxygenation2010Conference paper (Refereed)
  • 215.
    Fredly, Siv
    et al.
    Oslo University Hospital, Ullevål, Norway.
    Kvernebo, Knut
    Oslo University Hospital, Ullevål, Norway.
    Salerud, Göran
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Biophotonic Assessment of Microcirculation in Healthy Newborn Children2013Conference paper (Other academic)
  • 216.
    Fredriksson, Alexandru Grigorescu
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences.
    Trzebiatowska-Krzynska, Aleksandra
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Cardiology in Linköping.
    Dyverfeldt, Petter
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Engvall, Jan
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Faculty of Medicine and Health Sciences.
    Ebbers, Tino
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping.
    Turbulent kinetic energy in the right ventricle: Potential MR marker for risk stratification of adults with repaired Tetralogy of Fallot2018In: Journal of Magnetic Resonance Imaging, ISSN 1053-1807, E-ISSN 1522-2586, Vol. 47, no 4, p. 1043-1053Article in journal (Refereed)
    Abstract [en]

    Purpose: To assess right ventricular (RV) turbulent kinetic energy (TKE) in patients with repaired Tetralogy of Fallot (rToF) and a spectrum of pulmonary regurgitation (PR), as well as to investigate the relationship between these 4D flow markers and RV remodeling.

    Materials and Methods: Seventeen patients with rToF and 10 healthy controls were included in the study. Patients were divided into two groups based on PR fraction: one lower PR fraction group (11%) and one higher PR fraction group (>11%). Field strength/sequences: 3D cine phase contrast (4D flow), 2D cine phase contrast (2D flow), and balanced steady-state free precession (bSSFP) at 1.5T. Assessment: The RV volume was segmented in the morphologic short-axis images and TKE parameters were computed inside the segmented RV volume throughout diastole. Statistical tests: One-way analysis of variance with Bonferroni post-hoc test; unpaired t-test; Pearson correlation coefficients; simple and stepwise multiple regression models; intraclass correlation coefficient (ICC).

    Results: The higher PR fraction group had more remodeled RVs (140 6 25 vs. 107 6 22 [lower PR fraction, P < 0.01] and 93 6 15 ml/m2[healthy, P < 0.001] for RV end-diastolic volume index [RVEDVI]) and higher TKE values (5.95 6 3.15 vs. 2.23 6 0.81 [lower PR fraction, P < 0.01] and 1.91 6 0.78 mJ [healthy, P < 0.001] for Peak Total RV TKE). Multiple regression analysis between RVEDVI and 4D/2D flow parameters showed that Peak Total RV TKE was the strongest predictor of RVEDVI (R25 0.47, P 5 0.002).

    Conclusion: The 4D flow-specific TKE markers showed a slightly stronger association with RV remodeling than conventional 2D flow PR parameters. These results suggest novel hemodynamic aspects of PR in the development of late complications after ToF repair.

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  • 217. Order onlineBuy this publication >>
    Fredriksson, Ingemar
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Quantitative Laser Doppler Flowmetry2009Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Laser Doppler flowmetry (LDF) is virtually the only non-invasive technique, except for other laser speckle based techniques, that enables estimation of the microcirculatory blood flow. The technique was introduced into the field of biomedical engineering in the 1970s, and a rapid evolvement followed during the 1980s with fiber based systems and improved signal analysis. The first imaging systems were presented in the beginning of the 1990s.

    Conventional LDF, although unique in many aspects and elegant as a method, is accompanied by a number of limitations that may have reduced the clinical impact of the technique. The analysis model published by Bonner and Nossal in 1981, which is the basis for conventional LDF, is limited to measurements given in arbitrary and relative units, unknown and non-constant measurement volume, non-linearities at increased blood tissue fractions, and a relative average velocity estimate.

    In this thesis a new LDF analysis method, quantitative LDF, is presented. The method is based on recent models for light-tissue interaction, comprising the current knowledge of tissue structure and optical properties, making it fundamentally different from the Bonner and Nossal model. Furthermore and most importantly, the method eliminates or highly reduces the limitations mentioned above.

    Central to quantitative LDF is Monte Carlo (MC) simulations of light transport in tissue models, including multiple Doppler shifts by red blood cells (RBC). MC was used in the first proof-of-concept study where the principles of the quantitative LDF were tested using plastic flow phantoms. An optically and physiologically relevant skin model suitable for MC was then developed. MC simulations of that model as well as of homogeneous tissue relevant models were used to evaluate the measurement depth and volume of conventional LDF systems. Moreover, a variance reduction technique enabling the reduction of simulation times in orders of magnitudes for imaging based MC setups was presented.

    The principle of the quantitative LDF method is to solve the reverse engineering problem of matching measured and calculated Doppler power spectra at two different source-detector separations. The forward problem of calculating the Doppler power spectra from a model is solved by mixing optical Doppler spectra, based on the scattering phase functions and the velocity distribution of the RBC, from various layers in the model and for various amounts of Doppler shifts. The Doppler shift distribution is calculated based on the scattering coefficient of the RBC:s and the path length distribution of the photons in the model, where the latter is given from a few basal MC simulations.

    When a proper spectral matching is found, via iterative model parameters updates, the absolute measurement data are given directly from the model. The concentration is given in g RBC/100 g tissue, velocities in mm/s, and perfusion in g RBC/100 g tissue × mm/s. The RBC perfusion is separated into three velocity regions, below 1 mm/s, between 1 and 10 mm/s, and above 10 mm/s. Furthermore, the measures are given for a constant output volume of a 3 mm3 half sphere, i.e. within 1.13 mm from the light emitting fiber of the measurement probe.

    The quantitative LDF method was used in a study on microcirculatory changes in type 2 diabetes. It was concluded that the perfusion response to a local increase in skin temperature, a response that is reduced in diabetes, is a process involving only intermediate and high flow velocities and thus relatively large vessels in the microcirculation. The increased flow in higher velocities was expected, but could not previously be demonstrated with conventional LDF. The lack of increase in low velocity flow indicates a normal metabolic demand during heating. Furthermore, a correlation between the perfusion at low and intermediate flow velocities and diabetes duration was found. Interestingly, these correlations were opposites (negative for the low velocity region and positive for the mediate velocity region). This finding is well in line with the increased shunt flow and reduced nutritive capillary flow that has previously been observed in diabetes.

    List of papers
    1. Absolute flow velocity components in laser Doppler flowmetry
    Open this publication in new window or tab >>Absolute flow velocity components in laser Doppler flowmetry
    2006 (English)In: Proceedings of SPIE, the International Society for Optical Engineering, ISSN 0277-786X, E-ISSN 1996-756X, Vol. 6094, p. 60940A-Article in journal (Refereed) Published
    Abstract [en]

    A method to separate a Doppler power spectrum into a number of flow velocity components, measured in absolute units (mm/s), is presented. A Monte Carlo software was developed to track each individual Doppler shift, to determine the probability, p(n), for a photon to undergo n Doppler shifts. Given this shift distribution, a mathematical relationship was developed and used to calculate a Doppler power spectrum originating from a certain combination of velocity components. The non linear Levenberg-Marquardt optimization method could thus be used to fit the calculated and measured Doppler power spectra, giving the true set of velocity components in the measured sample. The method was evaluated using a multi tube flow phantom perfused with either polystyrene microspheres or undiluted/diluted human blood (hct = 0.45). It estimated the velocity components in the flow phantom well, during both low and high concentrations of moving scatterers (microspheres or blood). Thus, further development of the method could prove to be a valuable clinical tool to differentiate capillary blood flow.

    Place, publisher, year, edition, pages
    IEEE, 2006
    Keywords
    Laser Doppler flowmetry, LDF, Monte Carlo simulations, flow phantom, blood perfusion, scattering phase
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-11703 (URN)10.1117/12.659206 (DOI)
    Note
    Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Absolute flow velocity components in laser Doppler flowmetry, 2006, Proceedings of SPIE -- Volume 6094 Optical Diagnostics and Sensing VI. http://dx.doi.org/10.1117/12.659206. Copyright 2006 Society of Photo-Optical Instrumentation Engineers. This paper was published in Proceedings of SPIE -- Volume 6094 Optical Diagnostics and Sensing VI and is made available as an electronic reprint with permission of SPIE. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2017-12-13Bibliographically approved
    2. Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry
    Open this publication in new window or tab >>Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry
    2008 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 13, no 1, p. 14015-Article in journal (Refereed) Published
    Abstract [en]

    An optical microvascular skin model, valid at 780 nm, was developed. The model consisted of six layers with individual optical properties, and variable thicknesses and blood concentrations at three different blood flow velocities. Monte Carlo simulations were used to evaluate the impact of various model parameters on the traditional Laser Doppler flowmetry (LDF) measures. A set of reference Doppler power spectra was generated by simulating 7,000 configurations, varying the thickness and blood concentrations. Simulated spectra, at two different source detector separations, were compared with in vivo recorded spectra, using a non-linear search algorithm for minimizing the deviation between simulated and measured spectra. The model was validated by inspecting the thickness and blood concentrations which generated the best fit. These four parameters followed a priori expectations for the measurement situations, and the simulated spectra agreed well with the measured spectra for both detector separations. Average estimated dermal blood concentration was 0.08% at rest and 0.63% during heat provocation (44°C) on the volar side of the forearm, and 1.2% at rest on the finger pulp. The model is crucial for developing a technique for velocity-resolved absolute LDF measurements with known sampling volume, and can also be useful for other bio-optical modalities.

    Keywords
    laser Doppler velocimetry, simulations, biomedical optics, Doppler
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-11700 (URN)10.1117/1.2854691 (DOI)
    Note
    Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Optical microcirculatory skin model: Assessed by Monte Carlo simulations paired with in vivo laser Doppler flowmetry, 2008, Journal of Biomedical Optics, (13), 1, 14015. http://dx.doi.org/10.1117/1.2854691. Copyright 2008 Society of Photo-Optical Instrumentation Engineers. This paper was published in Journal of Biomedical Optics and is made available as an electronic reprint with permission of SPIE. One print or electronic copy may be made for personal use only. Systematic or multiple reproduction, distribution to multiple locations via electronic or other means, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited.Available from: 2008-04-29 Created: 2008-04-29 Last updated: 2017-12-13
    3. Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations
    Open this publication in new window or tab >>Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations
    2009 (English)In: JOURNAL OF BIOPHOTONICS, ISSN 1864-063X, Vol. 2, no 3, p. 178-184Article in journal (Refereed) Published
    Abstract [en]

    Two forced detection (FD) variance reduction Monte Carlo algorithms for image simulations of tissue-embedded objects with matched refractive index are presented. The principle of the algorithms is to force a fraction of the photon weight to the detector at each and every scattering event. The fractional weight is given by the probability for the photon to reach the detector without further interactions. Two imaging setups are applied to a tissue model including blood vessels, where the ID algorithms produce identical results as traditional brute force simulations, while being accelerated with two orders of magnitude. Extending the methods to include refraction mismatches is discussed.

    The principle of forced detection; a part of the photon weight. based on the probability of reaching the detector without further interactions, is forced to the detector at each and every scattering event.

    Keywords
    Monte Carlo simulations, diffuse scattering, variance reduction, Image simulation
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-17749 (URN)10.1002/jbio.200810048 (DOI)
    Note
    This is the pre-peer reviewed version of the following article: Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Forced detection Monte Carlo algorithms for accelerated blood vessel image simulations, 2009, JOURNAL OF BIOPHOTONICS, (2), 3, 178-184. which has been published in final form at: http://dx.doi.org/10.1002/jbio.200810048 Copyright: Wiley-Blackwell Available from: 2009-04-18 Created: 2009-04-17 Last updated: 2016-08-31Bibliographically approved
    4. Measurement depth and volume in laser Doppler flowmetry
    Open this publication in new window or tab >>Measurement depth and volume in laser Doppler flowmetry
    2009 (English)In: Microvascular Research, ISSN 0026-2862, E-ISSN 1095-9319, Vol. 78, no 1, p. 4-13Article in journal (Refereed) Published
    Abstract [en]

    A new method for estimating the measurement depth and volume in laser Doppler flowmetry (LDF) is presented. The method is based on Monte Carlo simulations of light propagation in tissue. The contribution from each individual Doppler shift is calculated and thereby multiple Doppler shifts are handled correctly. Different LDF setups for both probe based (0.0, 0.25, 0.5, and 1.2 mm source-detector separation) and imaging systems (0.5 and 2.0 mm beam diameter) are considered, at the wavelengths 543 nm, 633 nm, and 780 nm. Non-linear speckle pattern effects are accounted for in the imaging system setups. The effects of tissue optical properties, blood concentration, and blood oxygen saturation are evaluated using both homogeneous tissue models and a layered skin model. The results show that the effect on the measurement depth of changing tissue properties is comparable to the effect of changing the system setup, e.g. source-detector separation and wavelength. Skin pigmentation was found to have a negligible effect on the measurement depth. Examples of measurement depths are (values are given for a probe based system with 0.25 mm source-detector separation and an imaging system with a 0.5 mm beam diameter, respectively, both operating at 780 nm): muscle - 0.55/0.79 mm; liver - 0.40/0.53 mm; gray matter - 0.48/0.68 mm; white matter - 0.20/0.20 mm; index finger pulp - 0.41/0.53 mm; forearm skin - 0.53/0.56 mm; heat provoked forearm skin - 0.66/0.67 mm.

    Keywords
    Laser Doppler flowmetry, Laser Doppler perfusion monitoring, Laser Doppler perfusion imaging, Source-detector separation, Measurement volume, Sampling depth, Monte Carlo simulations, Tissue model, Multiple Doppler shifts
    National Category
    Engineering and Technology
    Identifiers
    urn:nbn:se:liu:diva-19656 (URN)10.1016/j.mvr.2009.02.008 (DOI)
    Note
    Original Publication: Ingemar Fredriksson, Marcus Larsson and Tomas Strömberg, Measurement depth and volume in laser Doppler flowmetry, 2009, Microvascular Research, (78), 1, 4-13. http://dx.doi.org/10.1016/j.mvr.2009.02.008 Copyright: Elsevier Science B.V., Amsterdam http://www.elsevier.com/ Available from: 2009-07-10 Created: 2009-07-10 Last updated: 2017-12-13Bibliographically approved
    5. Model-based quantitative laser Doppler flowmetry in skin
    Open this publication in new window or tab >>Model-based quantitative laser Doppler flowmetry in skin
    2010 (English)In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 5Article in journal (Refereed) Published
    Abstract [en]

    Laser Doppler Flowmetry (LDF) can be used for assessing the microcirculatory perfusion. However, conventional LDF (cLDF) gives only a relative perfusion estimate in an unknown measurement volume. To overcome these limitations a model-based analysis method for quantitative LDF (qLDF) is proposed. The method uses an inverse Monte Carlo technique with an adaptive three layer skin model. By analyzing the optimal model where measured and simulated LDF spectra using two different source-detector separations match, the absolute microcirculatory perfusion for a specified velocity region in a predefined volume is determined. The robustness of the qLDF method and how much it is affected by physiologically relevant variations in optical properties were evaluated using additional Monte Carlo simulations. When comparing qLDF to cLDF, a much smaller deviation from the true perfusion was attained. For physiologically relevant variations in the optical properties of static tissue and blood absorption, qLDF displayed errors <12%. Variations in the scattering properties of blood displayed larger errors (<58%). Evaluations on inhomogeneous models containing small blood vessels, hair and sweat glands displayed errors <5%. For extremely inhomogeneous models containing larger blood vessels, the error increased substantially, but this was detected by analyzing the qLDF model residual. The qLDF algorithm was applied to an in vivo local heat provocation. The perfusion increase was higher with qLDF than cLDF, due to non-linear effects in the latter. The qLDF showed that the perfusion increase was due to an increased amount of blood cells with a velocity > 1 mm/s.

    Place, publisher, year, edition, pages
    Society of Photo-optical Instrumentation Engineers, 2010
    Keywords
    laser Doppler flowmetry, microcirculation, tissue modeling, inverse Monte Carlo, quantitative measures, flow speed differentiation
    National Category
    Medical Laboratory and Measurements Technologies
    Identifiers
    urn:nbn:se:liu:diva-20445 (URN)10.1117/1.3484746 (DOI)000284837400046 ()
    Available from: 2009-09-08 Created: 2009-09-08 Last updated: 2017-12-13Bibliographically approved
    6. Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetry
    Open this publication in new window or tab >>Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetry
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The response to local heating (44oC for 20 min) was evaluated in 28 type 2 diabetes patients (DM) and 29 non-diabetes controls (ND). Microcirculatory perfusion was assessed using conventional and quantitative Laser Doppler flowmetry (cLDF and qLDF), respectively. The qLDF estimates perfusion in a physiological relevant unit (g RBC / 100 g tissue × mm/s) in a fixed output volume, separated into three velocity regions, v < 1 mm/s, 1 - 10 mm/s, and v > 10 mm/s. Perfusion in cLDF is given in arbitrary units with unknown velocity distribution and measurement volume.

    A significantly lower response in DM than in ND was found after heat provocation both for the initial peak and the plateau response, while no significant differences were found at baseline. The qLDF showed increased perfusion for the velocity regions 1-10 mm/s and above 10 mm/s, while no significant increase was found for v < 1 mm/s. In conclusion, we found a lowered LDF response to local heating in DM. The new qLDF method showed that the increased blood flow occurs in vessels with a velocity above 1 mm/s. Baseline qLDF-data indicated that a redistribution of flow to higher velocity regions was associated with longer DM duration and for DM a negative correlation between perfusion and BMI.

    National Category
    Medical Laboratory and Measurements Technologies Biomedical Laboratory Science/Technology Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:liu:diva-20447 (URN)
    Available from: 2009-09-08 Created: 2009-09-08 Last updated: 2010-01-14Bibliographically approved
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    Quantitative Laser Doppler Flowmetry
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  • 218.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Perimed AB, Järfälla, Sweden.
    Burdakov, Oleg
    Linköping University, Department of Mathematics, Optimization . Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Inverse Monte Carlo in a multilayered tissue model: merging diffuse reflectance spectroscopy and laser Doppler flowmetry2013In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 18, no 12, p. 127004-1-127004-14Article in journal (Refereed)
    Abstract [en]

    The tissue fraction of red blood cells (RBCs) and their oxygenation and speed-resolved perfusion areestimated in absolute units by combining diffuse reflectance spectroscopy (DRS) and laser Doppler flowmetry(LDF). The DRS spectra (450 to 850 nm) are assessed at two source–detector separations (0.4 and 1.2 mm), allowingfor a relative calibration routine, whereas LDF spectra are assessed at 1.2mmin the same fiber-optic probe. Data areanalyzed using nonlinear optimization in an inverse Monte Carlo technique by applying an adaptive multilayeredtissue model based on geometrical, scattering, and absorbing properties, as well as RBC flow-speed information.Simulations of 250 tissue-like models including up to 2000 individual blood vessels were used to evaluatethe method. The absolute root mean square (RMS) deviation between estimated and true oxygenation was 4.1percentage units, whereas the relative RMS deviations for the RBC tissue fraction and perfusion were 19% and23%, respectively. Examples of in vivo measurements on forearm and foot during common provocations arepresented. The method offers several advantages such as simultaneous quantification of RBC tissue fractionand oxygenation and perfusion from the same, predictable, sampling volume. The perfusion estimate is speedresolved, absolute (% RBC × mm∕s), and more accurate due to the combination with DRS.

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  • 219.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Hultman, Martin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Machine learning in multiexposure laser speckle contrast imaging can replace conventional laser Doppler flowmetry2019In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 24, no 1, article id 016001Article in journal (Refereed)
    Abstract [en]

    Laser speckle contrast imaging (LSCI) enables video rate imaging of blood flow. However, its relation to tissue blood perfusion is nonlinear and depends strongly on exposure time. By contrast, the perfusion estimate from the slower laser Doppler flowmetry (LDF) technique has a relationship to blood perfusion that is better understood. Multiexposure LSCI (MELSCI) enables a perfusion estimate closer to the actual perfusion than that using a single exposure time. We present and evaluate a method that utilizes contrasts from seven exposure times between 1 and 64 ms to calculate a perfusion estimate that resembles the perfusion estimate from LDF. The method is based on artificial neural networks (ANN) for fast and accurate processing of MELSCI contrasts to perfusion. The networks are trained using modeling of Doppler histograms and speckle contrasts from tissue models. The importance of accounting for noise is demonstrated. Results show that by using ANN, MELSCI data can be processed to LDF perfusion with high accuracy, with a correlation coefficient R = 1.000 for noise-free data, R = 0.993 when a moderate degree of noise is present, and R = 0.995 for in vivo data from an occlusion-release experiment. (C) The Authors. Published by SPIE under a Creative Commons Attribution 4.0 Unported License.

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  • 220.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    On the equivalence and differencesbetween laser Doppler flowmetry andlaser speckle contrast analysis2016In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 21, no 12, article id 126018Article in journal (Refereed)
    Abstract [en]

    Laser Doppler flowmetry (LDF) and laser speckle contrast analysis (LASCA) both utilize the spatiotemporalproperties of laser speckle patterns to assess microcirculatory blood flow in tissue. Although the techniquesanalyze the speckle pattern differently, there is a close relationship between them. We present atheoretical overview describing how the LDF power spectrum and the LASCA contrast can be calculatedfrom each other, and how both these can be calculated from an optical Doppler spectrum containing variousdegrees of Doppler shifted light. The theoretical relationships are further demonstrated using time-resolvedspeckle simulations. A wide range of Monte Carlo simulated tissue models is then used to show how perfusionestimates for LDF and LASCA are affected by changes in blood concentration and speed distribution, as well asby geometrical and optical properties. We conclude that perfusion estimates from conventional single exposuretime LASCA are in general more sensitive to changes in optical and geometrical properties and are less accuratein the prediction of real perfusion changes, especially speed changes. Since there is a theoretical one-to-onerelationship between Doppler power spectrum and contrast, one can conclude that those drawbacks with theLASCA technique can be overcome using a multiple exposure time setup.

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  • 221.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Vessel packaging effect in laser speckle contrast imaging and laser Doppler imaging2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 10, article id 106005Article in journal (Refereed)
    Abstract [en]

    Laser speckle-based techniques are frequently used to assess microcirculatory blood flow. Perfusion estimates are calculated either by analyzing the speckle fluctuations over time as in laser Doppler flowmetry (LDF), or by analyzing the speckle contrast as in laser speckle contrast imaging (LSCI). The perfusion estimates depend on the amount of blood and its speed distribution. However, the perfusion estimates are commonly given in arbitrary units as they are nonlinear and depend on the magnitude and the spatial distribution of the optical properties in the tissue under investigation. We describe how the spatial confinement of blood to vessels, called the vessel packaging effect, can be modeled in LDF and LSCI, which affect the Doppler power spectra and speckle contrast, and the underlying bio-optical mechanisms for these effects. As an example, the perfusion estimate is reduced by 25% for LDF and often more than 50% for LSCI when blood is located in vessels with an average diameter of 40 aem, instead of being homogeneously distributed within the tissue. This significant effect can be compensated for only with knowledge of the average diameter of the vessels in the tissue. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 222.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Nyström, Fredrik
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology .
    Länne, Toste
    Linköping University, Department of Medicine and Health Sciences. Linköping University, Department of Medicine and Health Sciences, Cardiology .
    Östgren, Carl Johan
    Linköping University, Department of Medicine and Health Sciences, General Practice. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Local Health Care Services in the West of Östergötland, West County Primary Health Care.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Microcirculatory changes in type 2 diabetes assessed with velocity resolved quantitative laser Doppler flowmetryManuscript (preprint) (Other academic)
    Abstract [en]

    The response to local heating (44oC for 20 min) was evaluated in 28 type 2 diabetes patients (DM) and 29 non-diabetes controls (ND). Microcirculatory perfusion was assessed using conventional and quantitative Laser Doppler flowmetry (cLDF and qLDF), respectively. The qLDF estimates perfusion in a physiological relevant unit (g RBC / 100 g tissue × mm/s) in a fixed output volume, separated into three velocity regions, v < 1 mm/s, 1 - 10 mm/s, and v > 10 mm/s. Perfusion in cLDF is given in arbitrary units with unknown velocity distribution and measurement volume.

    A significantly lower response in DM than in ND was found after heat provocation both for the initial peak and the plateau response, while no significant differences were found at baseline. The qLDF showed increased perfusion for the velocity regions 1-10 mm/s and above 10 mm/s, while no significant increase was found for v < 1 mm/s. In conclusion, we found a lowered LDF response to local heating in DM. The new qLDF method showed that the increased blood flow occurs in vessels with a velocity above 1 mm/s. Baseline qLDF-data indicated that a redistribution of flow to higher velocity regions was associated with longer DM duration and for DM a negative correlation between perfusion and BMI.

  • 223.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Linköping University, Faculty of Health Sciences.
    Salomonsson, Fredrik
    Perimed AB, Järfälla-Stockholm, Sweden.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Improved calibration procedure for laser Doppler perfusion monitors2011In: Optical Diagnostics and SensingXI: Toward Point-of-CareDiagnostics; and Design andPerformance Validation ofPhantoms Used in Conjunctionwith Optical Measurement ofTissue III / [ed] Robert J. Nordstrom; Gerard L. Coté, SPIE - International Society for Optical Engineering, 2011, p. 790602-1-790602-7Conference paper (Other academic)
    Abstract [en]

    Commercial laser Doppler perfusion monitors are calibrated using the perfusion value, i.e. the first order moment of the Doppler power spectrum, from a measurement in a standardized microsphere colloidal suspension under Brownian motion. The calibration perfusion value depends on several parameters of the suspension that are difficult to keep constant with adequate accuracy, such as the concentration, temperature and the microsphere size distribution. The calibration procedure itself may therefore introduce significant errors in the measured values.

    An altered calibration procedure, where the zero order moment is used is described and demonstrated in this paper. Since the above mentioned parameters only affect the frequency content of the Doppler power spectrum and not the total power, the zero order moment will be independent of those parameters. It is shown that the variation in the calibration value, as given by measurements on different scattering liquids with a wide range of scattering properties and temperatures, is only a few percent using the proposed method. For the conventional calibration procedure, this variation corresponds to an error introduced by merely a 1°C variation in the reference liquid temperature. The proposed calibration method also enables absolute level comparisons between measured and simulated Doppler power spectra.

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    Improved calibration procedure for laser Doppler perfusion monitors
  • 224.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Accuracy of vessel diameter estimated from a vessel packaging compensation in diffuse reflectance spectroscopy2011In: Clinical and Biomedical Spectroscopy and Imaging II / [ed] Nirmala Ramanujam, Jurgen Popp, SPIE - International Society for Optical Engineering, 2011, Vol. 8087, p. 8087 1M-1-8087 1M-8Conference paper (Other academic)
    Abstract [en]

     Light absorption in tissue is generally decreased when chromophores are spatially concentrated rather than being homogeneously distributed. In tissue, this applies to hemoglobin located in blood vessels (vessel packaging). In this paper, the diffusely reflected light from 41 tissue models with discrete blood vessels with diameters ranging from 6.25 to 100 μm were simulated using the Monte Carlo technique. A reverse engineering approach was then utilized to find the model that had an optimal spectral fit to each of the simulated models. The average vessel diameter was one fitting parameter in the adaptive model. The estimated vessel diameter from the optimal fit model was compared to the known diameter from the simulated models. Two different methods to calculate the vessel packaging effect were used, one existing based on a simple analytic expression and a new method based on path length distributions. Both methods had similar performance. For the new method, the absolute RMS deviation of the estimated vessel diameter was 5.5 μm for vessel diameters ≤ 25 μm, and the relative RMS deviation was 21 % for vessel diameters > 25 μm.

     

  • 225.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Inverse Monte Carlo method in a multilayered tissue model for diffuse reflectance spectroscopy2012In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 17, no 4, p. 047004-Article in journal (Refereed)
    Abstract [en]

    Model based data analysis of diffuse reflectance spectroscopy data enables the estimation of optical and structural tissue parameters. The aim of this study was to present an inverse Monte Carlo method based on spectra from two source-detector distances (0.4 and 1.2 mm), using a multilayered tissue model. The tissue model variables include geometrical properties, light scattering properties, tissue chromophores such as melanin and hemoglobin, oxygen saturation and average vessel diameter. The method utilizes a small set of presimulated Monte Carlo data for combinations of different levels of epidermal thickness and tissue scattering. The path length distributions in the different layers are stored and the effect of the other parameters is added in the post-processing. The accuracy of the method was evaluated using Monte Carlo simulations of tissue-like models containing discrete blood vessels, evaluating blood tissue fraction and oxygenation. It was also compared to a homogeneous model. The multilayer model performed better than the homogeneous model and all tissue parameters significantly improved spectral fitting. Recorded in vivo spectra were fitted well at both distances, which we previously found was not possible with a homogeneous model. No absolute intensity calibration is needed and the algorithm is fast enough for real-time processing.

  • 226.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Laser Doppler flowmetry2012In: Microcirculation imaging / [ed] Martin J. Leahy, Weinheim: Wiley-Blackwell, 2012, , p. 411p. 67-84Chapter in book (Other academic)
    Abstract [en]

    Adopting a multidisciplinary approach with input from physicists, researchers and medical professionals, this is the first book to introduce many different technical approaches for the visualization of microcirculation, including laser Doppler and laser speckle, optical coherence tomography and photo-acoustic tomography. It covers everything from basic research to medical applications, providing the technical details while also outlining the respective strengths and weaknesses of each imaging technique. Edited by an international team of top experts, this is the ultimate handbook for every clinician and researcher relying on microcirculation imaging.

  • 227.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Model-Based Quantification of Skin Microcirculatory Perfusion2014In: Computational Biophysics of the Skin / [ed] Bernard Querleux, Singapore: Pan Stanford Publishing, 2014, 1, p. 395-420Chapter in book (Other academic)
  • 228.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Larsson, Marcus
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Model-based quantitative laser Doppler flowmetry in skin2010In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 15, no 5Article in journal (Refereed)
    Abstract [en]

    Laser Doppler Flowmetry (LDF) can be used for assessing the microcirculatory perfusion. However, conventional LDF (cLDF) gives only a relative perfusion estimate in an unknown measurement volume. To overcome these limitations a model-based analysis method for quantitative LDF (qLDF) is proposed. The method uses an inverse Monte Carlo technique with an adaptive three layer skin model. By analyzing the optimal model where measured and simulated LDF spectra using two different source-detector separations match, the absolute microcirculatory perfusion for a specified velocity region in a predefined volume is determined. The robustness of the qLDF method and how much it is affected by physiologically relevant variations in optical properties were evaluated using additional Monte Carlo simulations. When comparing qLDF to cLDF, a much smaller deviation from the true perfusion was attained. For physiologically relevant variations in the optical properties of static tissue and blood absorption, qLDF displayed errors <12%. Variations in the scattering properties of blood displayed larger errors (<58%). Evaluations on inhomogeneous models containing small blood vessels, hair and sweat glands displayed errors <5%. For extremely inhomogeneous models containing larger blood vessels, the error increased substantially, but this was detected by analyzing the qLDF model residual. The qLDF algorithm was applied to an in vivo local heat provocation. The perfusion increase was higher with qLDF than cLDF, due to non-linear effects in the latter. The qLDF showed that the perfusion increase was due to an increased amount of blood cells with a velocity > 1 mm/s.

  • 229.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Saager, Rolf B.
    University of Calif Irvine, CA USA; University of Calif Irvine, CA USA.
    Durkin, Anthony J.
    University of Calif Irvine, CA USA.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. University of Calif Irvine, CA USA; University of Calif Irvine, CA USA.
    Evaluation of a multi-layer diffuse reflectance spectroscopy system using optical phantoms2017In: DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES X, SPIE-INT SOC OPTICAL ENGINEERING , 2017, Vol. 10056, article id UNSP 100560GConference paper (Refereed)
    Abstract [en]

    A fiber probe-based device for assessing microcirculatory parameters, especially red blood cell (RBC) tissue fraction, their oxygen saturation and speed resolved perfusion, has been evaluated using state-of-the-art multi-layer tissue simulating phantoms. The device comprises both diffuse reflectance spectroscopy (DRS) at two source-detector separations (0.4 and 1.2 mm) and laser Doppler flowmetry (LDF) and use an inverse Monte Carlo method for identifying the parameters of a multi-layered tissue model. First, model parameters affecting scattering, absorption and geometrical parameters are fitted to measured DRS spectra, then speed parameters are fitted to LDF spectra. In this paper, the accuracy of the spectral parameters is evaluated. The measured spectral shapes at the two source-detector separations were in good agreement with forward calculated spectral shapes. In conclusion, the multi-layer skin model based on spectral features of the included chromophores, can reliably estimate the tissue fraction of RBC, its oxygen saturation and the reduced scattering coefficient spectrum of the tissue. Furthermore, it was concluded that some freedom in the relative intensity difference between the two DRS channels is necessary in order to compensate for non-modeled surface structure effects.

  • 230.
    Fredriksson, Ingemar
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Perimed AB, Sweden.
    Saager, Rolf B.
    University of Calif Irvine, CA 92715 USA.
    Durkin, Anthony J.
    University of Calif Irvine, CA USA.
    Strömberg, Tomas
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. University of Calif Irvine, CA 92715 USA.
    Evaluation of a pointwise microcirculation assessment method using liquid and multilayered tissue simulating phantoms2017In: Journal of Biomedical Optics, ISSN 1083-3668, E-ISSN 1560-2281, Vol. 22, no 11, article id 115004Article in journal (Refereed)
    Abstract [en]

    A fiber-optic probe-based instrument, designed for assessment of parameters related to microcirculation, red blood cell tissue fraction (f(RBC)), oxygen saturation (S-O2), and speed resolved perfusion, has been evaluated using state-of-the-art tissue phantoms. The probe integrates diffuse reflectance spectroscopy (DRS) at two source-detector separations and laser Doppler flowmetry, using an inverse Monte Carlo method for identifying the parameters of a multilayered tissue model. Here, we characterize the accuracy of the DRS aspect of the instrument using (1) liquid blood phantoms containing yeast and (2) epidermis-dermis mimicking solid-layered phantoms fabricated from polydimethylsiloxane, titanium oxide, hemoglobin, and coffee. The rootmean-square (RMS) deviations for f(RBC) for the two liquid phantoms were 11% and 5.3%, respectively, and 11% for the solid phantoms with highest hemoglobin signatures. The RMS deviation for SO2 was 5.2% and 2.9%, respectively, for the liquid phantoms, and 2.9% for the solid phantoms. RMS deviation for the reduced scattering coefficient (mus), for the solid phantoms was 15% (475 to 850 nm). For the liquid phantoms, the RMS deviation in average vessel diameter (D) was 1 mu m. In conclusion, the skin microcirculation parameters fRBC and SO2, as well as, mu(s) and D are estimated with reasonable accuracy. (C) The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License.

  • 231.
    Fredriksson, Joakim
    et al.
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Andersson, Jonas
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Webbportal för arketypbaserade elektroniska patientjournaler: En testimplementation av openEHRs arkitektur2006Independent thesis Basic level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    One problem with electronic health record systems is that the health records are not built on a common architecture. This makes automatic exchange of patient data difficult. openEHR is a project that has developed an architecture that tries to solve this problem.

    The openEHR architecture uses something called archetypes. Archetypes are reusable models that limit, structure and explain what will be stored in the electronic health record that is built on this architecture.

    The main goal of this master thesis has been to find a method to generate a graphical user interface from an electronic health record created using archetypes. To solve this problem first archetypes and a system that generates health records from these had to be created. Then a Web portal has been developed that displays the generated health records.

    The Web portal can be used to demonstrate the graphical user interface of a system where both patients and authorized personnel can read patient records that are bases on the openEHR architecture.

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  • 232.
    Fullerton, A.
    et al.
    Leo Pharmaceutical Products Ltd.
    Stücker, M.
    Ruhr Universitet Bochum.
    Wilhelm, K-P.
    proDERM Institute for Applied Derm. Res. GmbH.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Anderson, C.
    Östergötlands Läns Landsting, Heart and Medicine Centre, Department of Dermatology and Venerology in Östergötland.
    Fisher, T.
    National Institute of Working Life, Solna.
    Nilsson, Gert
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Serup, J.
    Leo Pharmaceutical Products Ltd.
    Guidelines for visualisation of cutaneous blood flow by laser Doppler imaging2002In: Contact Dermatitis, ISSN 0105-1873, E-ISSN 1600-0536, Vol. 46, no 3, p. 129-140Article in journal (Refereed)
    Abstract [en]

    This report reviews how to set up a laser Doppler perfusion imaging system intended for visualization of skin blood perfusion, capture images and evaluate the results obtained. A brief summary of related papers published in the literature within the areas of skin irritant and allergy patch testing, microdialysis and skin tumour circulation is presented, as well as early applications within other fields such as diabetology, wound healing and microvascular research.

  • 233.
    Fytagoridis, Anders
    et al.
    Department of Pharmacologyand Clinical Neuroscience, Section of Neurosurgery, Umeå University, Umeå, Sweden.
    Åström, Mattias
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Samuelsson, Jörgen
    Unit of Functional and Stereotactic Neurosurgery, Department of Pharmacology and Clinical Neuroscience, Umeå University, Umeå.
    Blomstedt, Patric
    Department of Pharmacology and Clinical Neuroscience, Division of Neurosurgery, Umeå University, Umeå, Sweden.
    Deep Brain Stimulation of the Caudal Zona Incerta: Tremor Control in Relation to the Location of Stimulation Fields2016In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 94, no 6, p. 363-370Article in journal (Refereed)
    Abstract [en]

    Background: The caudal zona incerta (cZi) and posterior subthalamic area (PSA) are an emerging deep brain stimulation (DBS) target for essential tremor (ET). Objectives: To evaluate the efficacy of tremor control in relation to the anatomical locations of stimulation fields in 50 patients with ET and DBS of the cZi. Methods: A total of 240 contacts were evaluated separately with monopolar stimulation, and amplitudes were optimized for improvement of tremor and hand function. Stimulation fields, i.e., volumes of neural activation, were simulated for each optimized setting and assembled into probabilistic stimulation maps (PSMs). Results: There were differences in the anatomical distribution of PSMs associated with good versus poor tremor control. The location of PSMs which achieved good and excellent tremor control corresponded well with the PSM for the clinically used settings, and they were located within the superior part of the PSA. Conclusions: PSMs may serve as a useful tool for defining the most efficacious anatomical location of stimulation. The best tremor control in this series of cZi DBS was achieved with stimulation of the superior part of the PSA, which corresponds to the final part of the cerebellothalamic projections before they reach the ventral lateral thalamus.

  • 234.
    Gaeta, Stephen
    et al.
    Duke Univ, NC USA.
    Dyverfeldt, Petter
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Eriksson, Jonatan
    Linköping University, Faculty of Medicine and Health Sciences. Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine.
    Carlhäll, Carljohan
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Ebbers, Tino
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Bolger, Ann F
    Linköping University, Department of Medical and Health Sciences, Division of Cardiovascular Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Heart and Medicine Center, Department of Clinical Physiology in Linköping. Univ Calif San Francisco, CA 94143 USA.
    Fixed volume particle trace emission for the analysis of left atrial blood flow using 4D Flow MRI2018In: Magnetic Resonance Imaging, ISSN 0730-725X, E-ISSN 1873-5894, Vol. 47, p. 83-88Article in journal (Refereed)
    Abstract [en]

    4D Flow MRI has been used to quantify normal and deranged left ventricular blood flow characteristics on the basis of functionally distinct flow components. However, the application of this technique to the atria is challenging due to the presence of continuous inflow. This continuous inflow necessitates plane-based emission of particle traces from the inlet veins, leading to particles that represents different amounts of blood, and related quantification errors. The purpose of this study was to develop a novel fixed-volume approach for particle tracing and employ this method to develop quantitative analysis of 4D blood flow characteristics in the left atrium. 4D Flow MRI data were acquired during free-breathing using a navigator-gated gradient-echo sequence in three volunteers at 1.5 T. Fixed-volume particle traces emitted from the pulmonary veins were used to visualize left atrial blood flow and to quantitatively separate the flow into two functionally distinct flow components: Direct flow = particle traces that enter and leave the atrium in one heartbeat, Retained flow = particle traces that enter the atrium and remains there for one cardiac cycle. Flow visualization based on fixed-volume traces revealed that, beginning in early ventricular systole, flow enters the atrium and engages with residual blood volume to form a vortex. In early diastole during early ventricular filling, the organized vortical flow is extinguished, followed by formation of a second transient atrial vortex. Finally, in late diastole during atrial contraction, a second acceleration of blood into the ventricle is seen. The direct and retained left atrial flow components were between 44 and 57% and 43-56% of the stroke volume, respectively. In conclusion, fixed volume particle tracing permits separation of left atrial blood flow into different components based on the transit of blood through the atrium.

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  • 235.
    Gaihede, Mihael
    et al.
    Aalborg University Hospital, Denmark.
    Cros, Olivier
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Borga, Magnus
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology.
    Pauwels, Elin
    University of Ghent, Belgium.
    Dirckx, Joris
    University of Antwerp, Belgium.
    Micro CT-scanning of the mastoid. Micro-channels supporting a high vascular supply of the mastoid mucosa and its role in pressure regulation2013Conference paper (Other academic)
  • 236.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Bioelectronic nanofibre scaffolds for tissue engineering and whole-cell biosensors2014Conference paper (Refereed)
  • 237.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Kozak Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Smart Electroactive Scaffolds for Cardiac Tissue Regeneration2014Conference paper (Refereed)
  • 238.
    Gelmi, Amy
    et al.
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Zhang, Jiabin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Cieslar-Pobuda, Artur
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Ljunggren, Monika
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Los, Marek
    Linköping University, Department of Clinical and Experimental Medicine, Division of Cell Biology. Linköping University, Faculty of Medicine and Health Sciences.
    Rafat, Mehrdad
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Jager, Edwin
    Linköping University, Department of Physics, Chemistry and Biology, Biosensors and Bioelectronics. Linköping University, Faculty of Science & Engineering.
    Electroactive polymer scaffolds for cardiac tissue engineering2015In: Proc. SPIE 9430, Electroactive Polymer Actuators and Devices (EAPAD) 2015 / [ed] Bar-Cohen, SPIE - International Society for Optical Engineering, 2015, Vol. 9430, p. 94301T-1-94301T-7Conference paper (Refereed)
    Abstract [en]

    By-pass surgery and heart transplantation are traditionally used to restore the heart’s functionality after a myocardial Infarction (MI or heart attack) that results in scar tissue formation and impaired cardiac function. However, both procedures are associated with serious post-surgical complications. Therefore, new strategies to help re-establish heart functionality are necessary. Tissue engineering and stem cell therapy are the promising approaches that are being explored for the treatment of MI. The stem cell niche is extremely important for the proliferation and differentiation of stem cells and tissue regeneration. For the introduction of stem cells into the host tissue an artificial carrier such as a scaffold is preferred as direct injection of stem cells has resulted in fast stem cell death. Such scaffold will provide the proper microenvironment that can be altered electronically to provide temporal stimulation to the cells. We have developed an electroactive polymer (EAP) scaffold for cardiac tissue engineering. The EAP scaffold mimics the extracellular matrix and provides a 3D microenvironment that can be easily tuned during fabrication, such as controllable fibre dimensions, alignment, and coating. In addition, the scaffold can provide electrical and electromechanical stimulation to the stem cells which are important external stimuli to stem cell differentiation. We tested the initial biocompatibility of these scaffolds using cardiac progenitor cells (CPCs), and continued onto more sensitive induced pluripotent stem cells (iPS). We present the fabrication and characterisation of these electroactive fibres as well as the response of increasingly sensitive cell types to the scaffolds.

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  • 239. Order onlineBuy this publication >>
    Georgiopoulos, Charalampos
    Linköping University, Department of Medical and Health Sciences, Division of Radiological Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Radiology in Linköping.
    Imaging Studies of Olfaction in Health and Parkinsonism2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Olfactory loss is a common non-motor symptom of Parkinson’s disease (PD), often preceding the cardinal motor symptoms of the disease. The aim of this thesis was to: (a) evaluate whether olfactory examination can increase diagnostic accuracy, and (b) study the structural and functional neural basis of olfactory dysfunction in PD with different applications of Magnetic Resonance Imaging (MRI).

    Paper I was a comparison of the diagnostic accuracy between a simple smell identification test and DaTSCAN Single Photon Emission Computerized Tomography (SPECT), a nuclear medicine tomographic imaging technique that is commonly used in patients with suspected parkinsonism. The results indicate that smell test is inferior to DaTSCAN SPECT, but the combination of these two methods can lead to improved diagnostic accuracy.

    Paper II showed that diffusion MRI could detect discrete microstructural changes in the white matter of brain areas that participate in higher order olfactory neurotransmission, whereas MRI with Magnetization Transfer contrast could not.

    Paper III was a methodological study on how two different acquisition parameters can affect the activation pattern of olfactory brain areas, as observed with functional MRI (fMRI). The results indicate that brief olfactory stimulation and fast sampling rate should be preferred on olfactory fMRI studies.

    Paper IV used olfactory fMRI and resting-state fMRI in order to elucidate potentially altered activation patterns and functional connectivity within olfactory brain areas, between PD patients and healthy controls. Olfactory fMRI showed that olfactory impairment in PD is associated with significantly lower recruitment of the olfactory network. Resting-state fMRI did not detect any significant changes in the functional connectivity within the olfactory network of PD patients.

    In conclusion, the included studies provide evidence of: (a) disease-related structural and functional changes in olfactory brain areas, and (b) beneficial addition of olfactory tests in the clinical work-up of patients with parkinsonism.

    List of papers
    1. The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes
    Open this publication in new window or tab >>The diagnostic value of dopamine transporter imaging and olfactory testing in patients with parkinsonian syndromes
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    2015 (English)In: Journal of Neurology, ISSN 0340-5354, E-ISSN 1432-1459, Vol. 262, no 9, p. 2154-2163Article in journal (Refereed) Published
    Abstract [en]

    The aim of the study was to compare the efficacy of olfactory testing and presynaptic dopamine imaging in diagnosing Parkinsons disease (PD) and atypical parkinsonian syndromes (APS); to evaluate if the combination of these two diagnostic tools can improve their diagnostic value. A prospective investigation of 24 PD patients, 16 APS patients and 15 patients with non-parkinsonian syndromes was performed during an 18-month period. Single photon emission computed tomography with the presynaptic radioligand I-123-FP-CIT (DaTSCAN (R)) and olfactory testing with the Brief 12-item Smell Identification Test (B-SIT) were performed in all patients. DaTSCAN was analysed semi-quantitatively, by calculating two different striatal uptake ratios, and visually according to a predefined ranking scale. B-SIT score was significantly lower for PD patients, but not significantly different between APS and non-parkinsonism. The visual assessment of DaTSCAN had higher sensitivity, specificity and diagnostic accuracy compared to olfactory testing. Most PD patients (75 %) had visually predominant dopamine depletion in putamen, while most APS patients (56 %) had visually severe dopamine depletion both in putamen and in caudate nucleus. The combination of DaTSCAN and B-SIT led to a higher rate of correctly classified patients. Olfactory testing can distinguish PD from non-parkinsonism, but not PD from APS or APS from non-parkinsonism. DaTSCAN is more efficient than olfactory testing and can be valuable in differentiating PD from APS. However, combining olfactory testing and DaTSCAN imaging has a higher predictive value than these two methods separately.

    Place, publisher, year, edition, pages
    Springer Berlin/Heidelberg, 2015
    Keywords
    Parkinsons disease; Atypical parkinsonism; Parkinsonian syndromes; Olfaction; I-123-FP-CIT SPECT
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:liu:diva-122669 (URN)10.1007/s00415-015-7830-4 (DOI)000363035400018 ()26122543 (PubMedID)
    Note

    Funding Agencies|Ostergotland County Council (ALF); Swedish Parkinsons Foundation

    Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2019-03-05Bibliographically approved
    2. Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging
    Open this publication in new window or tab >>Olfactory Impairment in Parkinsons Disease Studied with Diffusion Tensor and Magnetization Transfer Imaging
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    2017 (English)In: Journal of Parkinson's Disease, ISSN 1877-7171, E-ISSN 1877-718X, Vol. 7, no 2, p. 301-311Article in journal (Refereed) Published
    Abstract [en]

    Background: Olfactory impairment is an early manifestation of Parkinsons disease (PD). Diffusion Tensor Imaging (DTI) and Magnetization Transfer (MT) are two imaging techniques that allow noninvasive detection of microstructural changes in the cerebral white matter. Objective: To assess white matter alterations associated with olfactory impairment in PD, using a binary imaging approach with DTI and MT. Methods: 22 PD patients and 13 healthy controls were examined with DTI, MT and an odor discrimination test. DTI data were first analyzed with tract-based spatial statistics (TBSS) in order to detect differences in fractional anisotropy, mean, radial and axial diffusivity between PD patients and controls. Voxelwise randomized permutation was employed for the MT analysis, after spatial and intensity normalization. Additionally, ROI analysis was performed on both the DTI and MT data, focused on the white matter adjacent to olfactory brain regions. Results: Whole brain voxelwise analysis revealed decreased axial diffusivity in the left uncinate fasciculus and the white matter adjacent to the left olfactory sulcus of PD patients. ROI analysis demonstrated decreased axial diffusivity in the right orbitofrontal cortex, as well as decreased mean diffusivity and axial diffusivity in the white matter of the left entorhinal cortex of PD patients. There were no significant differences regarding fractional anisotropy, radial diffusivity or MT between patients and controls. Conclusions: ROI analysis of DTI could detect microstructural changes in the white matter adjacent to olfactory areas in PD patients, whereas MT imaging could not.

    Place, publisher, year, edition, pages
    IOS PRESS, 2017
    Keywords
    Parkinson disease; smell; diffusion tensor imaging; magnetization transfer contrast imaging
    National Category
    Neurology
    Identifiers
    urn:nbn:se:liu:diva-138300 (URN)10.3233/JPD-161060 (DOI)000401801600010 ()28482644 (PubMedID)
    Note

    Funding Agencies|Swedish Parkinson Foundation; Linkoping University Hospital Research Fund; ALF Grants from Region Ostergotland

    Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2019-03-05
    3. Olfactory fMRI: Implications of Stimulation Length and Repetition Time
    Open this publication in new window or tab >>Olfactory fMRI: Implications of Stimulation Length and Repetition Time
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    2018 (English)In: Chemical Senses, ISSN 0379-864X, E-ISSN 1464-3553, Vol. 43, no 6, p. 389-398Article in journal (Refereed) Published
    Abstract [en]

    Studying olfaction with functional magnetic resonance imaging (fMRI) poses various methodological challenges. This study aimed to investigate the effects of stimulation length and repetition time (TR) on the activation pattern of 4 olfactory brain regions: the anterior and the posterior piriform cortex, the orbitofrontal cortex, and the insula. Twenty-two healthy participants with normal olfaction were examined with fMRI, with 2 stimulation lengths (6 s and 15 s) and 2 TRs (0.901 s and 1.34 s). Data were analyzed using General Linear Model (GLM), Tensorial Independent Component Analysis (TICA), and by plotting the event-related time course of brain activation in the 4 olfactory regions of interest. The statistical analysis of the time courses revealed that short TR was associated with more pronounced signal increase and short stimulation was associated with shorter time to peak signal. Additionally, both long stimulation and short TR were associated with oscillatory time courses, whereas both short stimulation and short TR resulted in more typical time courses. GLM analysis showed that the combination of short stimulation and short TR could result in visually larger activation within these olfactory areas. TICA validated that the tested paradigm was spatially and temporally associated with a functionally connected network that included all 4 olfactory regions. In conclusion, the combination of short stimulation and short TR is associated with higher signal increase and shorter time to peak, making it more amenable to standard GLM-type analyses than long stimulation and long TR, and it should, thus, be preferable for olfactory fMRI.

    Place, publisher, year, edition, pages
    OXFORD UNIV PRESS, 2018
    Keywords
    fMRI; olfaction; smell; repetition time
    National Category
    Neurosciences
    Identifiers
    urn:nbn:se:liu:diva-149862 (URN)10.1093/chemse/bjy025 (DOI)000438293600001 ()29726890 (PubMedID)
    Note

    Funding Agencies|Swedish Parkinson Foundation, Linkoping University Hospital Research Fund; ALF Grants from Region Ostergotland

    Available from: 2018-08-02 Created: 2018-08-02 Last updated: 2019-04-17
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    Imaging Studies of Olfaction in Health and Parkinsonism
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  • 240.
    Ghaffari, Ghazaleh
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Estimation of Stapedius-Muscle Activation using Ear Canal Absorbance Measurements: An Application of Signal Processing in Physiological Acoustics2013Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
    Abstract [en]

    The stapedius muscle, which is located in the middle ear, goes into contraction when the ear is exposed to high sound intensities. This muscle activation is called ‘the acoustic reflex’. Measurement of the acoustic reflex is clinically of importance since it can reveal diagnostic information about the middle ear’s pathologies. Moreover, this muscle-activation alters the acoustic characteristics of the middle ear (i.e. the acoustic impedance and the power reflectance), which in turn, can significantly manipulate one’s perception of sounds. In the present study, these acoustic characteristics are measured in the ear canal by means of absorbance measures using equivalent Thevenin circuit theory. The quantities are then compared to form the shift responses between the baseline (before the activation) and the post-activator effect. This project investigates the shifts in power reflectance and admittance of the middle ear caused by the stapedius-muscle contraction. The wideband characterization (0.1- 8 kHz) of these acoustic reflex-induced shifts is achieved using chirp signals as a probe and through ipsilateral broadband noise activator. The data acquisition and signal processing of the project are carried out using MATLAB software. The hardware consists of National Instruments USB-6212 data acquisition interface and low noise microphone system Etymotic Research ER-10B+. A group of 10 adults including 5 males and 5 females are recruited as the participants for the project. The measurements of the reflectance shifts indicate that the most robust frequency region affected by the acoustic reflex is up to 4 kHz whereas for the admittance shifts, this region is up to 2 kHz. In addition, it is shown that the stapedius-muscle contraction leads to the attenuation of the lowfrequency transmission into the middle ear (less than 1 kHz) consistent with a stiffnesscontrolled system in this range of frequencies. In contrast, the results imply that the activation of the stapedius muscle leads to a slight enhancement of the frequency transmission in the range of 1-4 kHz (corresponding to the speech frequency band). These findings suggest a beneficial role for the stapedius-muscle contraction in the perception of speech during vocalization. Furthermore, the implemented methods in this project  can be useful in better understanding the effect of the stapedius-muscle contraction on the speech perception both in normal hearing and hearing impaired persons.

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  • 241.
    Gharebhaghi, Arash
    et al.
    Linköping University, Department of Biomedical Engineering.
    Hult, Peter
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, Faculty of Science & Engineering.
    Graphic User Interface for Heart Sound Signal Analysis2010Conference paper (Other academic)
  • 242.
    Gharehbaghi, A.
    et al.
    Malardalen Univ, Sweden.
    Sepehri, Amir A.
    CAPIS Biomed Res and Dept Ctr, Belgium.
    Linden, Maria
    Malardalen Univ, Sweden.
    Babic, Ankica
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    A Hybrid Machine Learning Method for Detecting Cardiac Ejection Murmurs2018In: EMBEC and NBC 2017, SPRINGER-VERLAG SINGAPORE PTE LTD , 2018, Vol. 65, p. 787-790Conference paper (Refereed)
    Abstract [en]

    This paper presents a novel method for detecting cardiac ejection murmurs from other pathological and physiological heart murmurs in children. The proposed method combines a hybrid model and a time growing neural network for an improved detection even in mild condition. Children with aortic stenosis and pulmonary stenosis comprised the patient category against the reference category containing mitral regurgitation, ventricular septal defect, innocent murmur and normal (no murmur) conditions. In total, 120 referrals to a children University hospital participated to the study after giving their informed consent. Confidence interval of the accuracy, sensitivity and specificity is estimated to be 87.2%-88.8%, 83.4%-86.9% and 88.3%-90.0%, respectively.

  • 243.
    Gharehbaghi, Arash
    et al.
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    Borga, Magnus
    Linköping University, Department of Biomedical Engineering, Medical Informatics. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Janerot Sjöberg, Birgitta
    Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden; Department of Clinical Physiology, Karolinska University Hospital, Stockholm, Sweden; School of Technology and Health, KTH Royal Institute of Technology, Stockholm, Sweden.
    Per, Ask
    Linköping University, Department of Biomedical Engineering, Physiological Measurements. Linköping University, The Institute of Technology.
    A novel method for discrimination between innocent and pathological heart murmurs2015In: Medical Engineering and Physics, ISSN 1350-4533, E-ISSN 1873-4030, Vol. 37, no 7, p. 674-682Article in journal (Refereed)
    Abstract [en]

    This paper presents a novel method for discrimination between innocent and pathological murmurs using the growing time support vector machine (GTSVM). The proposed method is tailored for characterizing innocent murmurs (IM) by putting more emphasis on the early parts of the signal as IMs are often heard in early systolic phase. Individuals with mild to severe aortic stenosis (AS) and IM are the two groups subjected to analysis, taking the normal individuals with no murmur (NM) as the control group. The AS is selected due to the similarity of its murmur to IM, particularly in mild cases. To investigate the effect of the growing time windows, the performance of the GTSVM is compared to that of a conventional support vector machine (SVM), using repeated random sub-sampling method. The mean value of the classification rate/sensitivity is found to be 88%/86% for the GTSVM and 84%/83% for the SVM. The statistical evaluations show that the GTSVM significantly improves performance of the classification as compared to the SVM.

  • 244.
    Gharehbaghi, Arash
    et al.
    Malardalen Univ, Sweden.
    Sepehri, Amir A.
    CAPIS Biomed Res and Dev Ctr, Belgium.
    Babic, Ankica
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Univ Bergen, Norway.
    Forth Heart Sound Detection Using Backward Time-Growing Neural Network2020In: PROCEEDINGS OF THE INTERNATIONAL CONFERENCE ON MEDICAL AND BIOLOGICAL ENGINEERING, CMBEBIH 2019, SPRINGER , 2020, Vol. 73, p. 341-345Conference paper (Refereed)
    Abstract [en]

    This paper presents a novel method for processing heart sound signal for screening forth heart sound (S4). The proposed method is based on time growing neural network with a new scheme, which we call the Backward Time-Growing Neural Network (BTGNN). The BTGNN is trained for detecting S4 in recordings of heart sound signal. In total, 83 children patients, referred to a children University hospital, participated in the study. The collected signals are composed of the subjects with and without S4 for training and testing the method. Performance of the method is evaluated using the Leave-One-Out and the repeated random sub sampling methods. The accuracy/sensitivity of the method is estimated to be 88.3%/82.4% and the structural risk is calculated to be 18.3% using repeated random sub sampling and the A-Test methods, respectively.

  • 245.
    Glasin, Joakim
    et al.
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Henricson, Joakim
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Lindberg, Lars-Göran
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Björk Wilhelms, Daniel
    Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Local Health Care Services in Central Östergötland, Department of Emergency Medicine in Linköping.
    Wireless vitals: Proof of concept for wireless patient monitoring in an emergency department setting2019In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 12, no 4, article id e201800275Article in journal (Refereed)
    Abstract [en]

    Vital sign assessment is a common task in emergency medicine, but resources for continuous monitoring are restricted, data is often recorded manually, and entangled wires cause frustration. Therefore, we designed a small, wireless photoplethysmographic device capable of continuously assessing pulse, respiratory frequency and oxygen saturation on the sternum and tested the performance and feasibility in an emergency department setting. Fifty (56.3 20.2 years), consenting emergency patients (29 male) were recruited. Heart rate, respiratory rate and oxygen saturation were recorded simultaneously using the device and standard monitoring equipment. Data was compared using Bland-Altman plotting (heart rate, respiratory rate) and mean difference (oxygen saturation). The bias for heart- and respiratory rate was 0.4 (limits of agreements -11.3, 12.2 and -6.1, 7.0). Mean difference for oxygen saturation was -0.21 +/- 2.35%. This may be the first wireless device to use photoplethysmography on the sternum for vital sign assessment. We noted good agreement with standard monitors, but lack of standardization in data processing between monitoring systems may limit the generalizability of these findings. Although further improvements are needed, the feasibility of this approach provides proof of concept for a new paradigm of large scale, wireless patient monitoring.

  • 246.
    Gollvik, Martin
    Linköping University, Department of Biomedical Engineering.
    Metamodeling for ultra-fast parameter estimation: Theory and evaluation of use in real-time diagnosis of diffuse liver disease2014Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Diffuse liver disease is a growing problem and a major cause of death worldwide. In the final stages the treatment often involves liver resection or transplant and in deciding what course of action is to be taken it is crucial to have a correct assessment of the function of the liver. The current “gold standard” for this assessment is to take a liver biopsy which has a number of disadvantages. As an alternative, a method involving magnetic resonance imaging and mechanistic modeling of the liver has been developed at Linköping University. One of the obstacles for this method to overcome in order to reach clinical implementation is the speed of the parameter estimation. In this project the methodology of metamodeling is tested as a possible solution to this speed problem. Metamodeling involve making models of models using extensive model simulations and mathematical tools. With the use of regression methods, clustering algorithms, and optimization, different methods for parameter estimation have been evaluated. The results show that several, but not all, of the parameters could be accurately estimated using metamodeling and that metamodeling could be a highly useful tool when modeling biological systems. With further development, metamodeling could bring this non-invasive method for estimation of liver function a major step closer to application in the clinic.

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    Martin Gollvik master thesis
  • 247.
    Gorgolewski, Krzysztof J.
    et al.
    Department of Psychology, Stanford University, Stanford, California, United States of America.
    Alfaro-Almagro, Fidel
    Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Oxford University, Oxford, United Kingdom.
    Auer, Tibor
    Department of Psychology, Royal Holloway University of London, Egham, United Kingdom.
    Bellec, Pierre
    Centre de Recherche de l’Institut Universitaire Gériatrique de Montréal, Montreal, Canada; Department of computer science and operations research, Université de Montréal, Montreal, Canada.
    Capotă, Michel
    Parallel Computing Lab, Intel Corporation, Santa Clara, CA & Hillsboro, Oregon, United States of America.
    Chakravarty, M. Mallar
    Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry McGill University, Montreal, Canada.
    Churchill, Nathan W.
    Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael’s Hospital, Ontario, Canada.
    Li Cohen, Alexander
    Department of Neurology, Boston Children’s Hospital, Boston, Massachusetts, United States of America.
    Craddock, R. Cameron
    Computational Neuroimaging Lab, Center for Biomedical Imaging and Neuromodulation, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York, United States of America; Center for the Developing Brain, Child Mind Institute, New York, New York, United States of America.
    Devenyi, Gabriel A.
    Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry McGill University, Montreal, Canada.
    Eklund, Anders
    Linköping University, Center for Medical Image Science and Visualization (CMIV). Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Department of Computer and Information Science, Statistics. Linköping University, Faculty of Science & Engineering.
    Esteban, Oscar
    Department of Psychology, Stanford University, Stanford, California, United States of America.
    Flandin, Guillaume
    Wellcome Trust Centre for Neuroimaging, London, United Kingdom.
    Ghosh, Satrajit S.
    McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America; Department of Otolaryngology, Harvard Medical School, Boston, Massachusetts, United States of America.
    Guntupalli, J. Swaroop
    Department of Psychological and Brain Sciences, Dartmouth College, Hanover, New Hampshire, United States of America.
    Jenkinson, Mark
    Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB), Oxford University, Oxford, United Kingdom.
    Keshavan, Anisha
    UC Berkeley-UCSF Graduate Program in Bioengineering, San Francisco, California, United States of America.
    Kiar, Gregory
    Center for Imaging Science, Johns Hopkins University, Baltimore, Maryland, United States of America; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
    Liem, Franziskus
    University Research Priority Program "Dynamics of Healthy Aging", University of Zurich, Zurich, Switzerland.
    Reddy Raamana, Pradeep
    Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
    Raffelt, David
    Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
    Steele, Cristopher J.
    Douglas Mental Health University Institute, McGill University, Montreal, Canada; Department of Psychiatry McGill University, Montreal, Canada.
    Quirion, Pierre-Olivier
    Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Smith, Robert E.
    Florey Institute of Neuroscience and Mental Health, Melbourne, Victoria, Australia.
    Strother, Stephen C.
    Rotman Research Institute, Baycrest Health Sciences, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
    Varoquaux, Gaël
    Parietal team, INRIA Saclay Ile-de-France, Palaiseau, France.
    Wang, Yida
    Parallel Computing Lab, Intel Corporation, Santa Clara, CA & Hillsboro, Oregon, United States of America.
    Yarkoni, Tal
    Department of Psychology, University of Texas at Austin, Austin, Texas, United States of America.
    Poldrack, Russel A.
    Department of Psychology, Stanford University, Stanford, California, United States of America.
    BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods2017In: PloS Computational Biology, ISSN 1553-734X, E-ISSN 1553-7358, Vol. 13, no 3, article id e1005209Article in journal (Refereed)
    Abstract [en]

    The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms.

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  • 248.
    Granlund, Gösta H.
    Linköping University, Department of Electrical Engineering. Linköping University, The Institute of Technology.
    A Nonlinear, Image-content Dependent Measure of Image Quality1977Report (Other academic)
    Abstract [en]

    In recent years, considerable research effort has been devoted to the development of useful descriptors for image quality. The attempts have been hampered by i n complete understanding of the operation of the human visual system. This has made it difficult to relate physical measures and perceptual traits.

    A new model for determination of image quality is proposed. Its main feature is that it tries to invoke image content into consideration. The model builds upon a theory of image linearization, which means that the information in an image can well enough be represented using linear segments or structures within local spatial regions and frequency ranges. This implies a l so a suggestion that information in an image has to do with one- dimensional correlations. This gives a possibility to separate image content from noise in images, and measure them both.

    Also a hypothesis is proposed that the visual system of humans does in fact perform such a linearization.

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    Nonlinear, Image-content Dependent Measure of Image Quality
  • 249.
    Grip, Helena
    et al.
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Öhberg, Fredrik
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Wiklund, Urban
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Sterner, Ylva
    Community Medicine and Rehabilitation, University Hospital, Umeå, Sweden.
    Karlsson, J. Stefan
    Department of Biomedical Engineering and Informatics, University Hospital, Umeå, Sweden.
    Gerdle, Björn
    Linköping University, Department of Clinical and Experimental Medicine, Rehabilitation Medicine. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Centre for Medicine, Pain and Rehabilitation Centre.
    Classification of Neck Movement Patterns Related to Whiplash-Associated Disorders Using Neural Networks2003In: IEEE transactions on information technology in biomedicine, ISSN 1089-7771, E-ISSN 1558-0032, Vol. 7, no 4, p. 412-418Article in journal (Refereed)
    Abstract [en]

    This paper presents a new method for classification of neck movement patterns related to Whiplash-associated disorders (WAD) using a resilient backpropagation neural network (BPNN). WAD are a common diagnosis after neck trauma, typically caused by rear-end car accidents. Since physical injuries seldom are found with present imaging techniques, the diagnosis can be difficult to make. The active range of the neck is often visually inspected in patients with neck pain, but this is a subjective measure, and a more objective decision support system, that gives a reliable and more detailed analysis of neck movement pattern, is needed. The objective of this study was to evaluate the predictive ability of a BPNN, using neck movement variables as input. Three-dimensional (3-D) neck movement data from 59 subjects with WAD and 56 control subjects were collected with a ProReflex system. Rotation angle and angle velocity were calculated using the instantaneous helical axis method and motion variables were extracted. A principal component analysis was performed in order to reduce data and improve the BPNN performance. BPNNs with six hidden nodes had a predictivity of 0.89, a sensitivity of 0.90 and a specificity of 0.88, which are very promising results. This shows that neck movement analysis combined with a neural network could build the basis of a decision support system for classifying suspected WAD, even though further evaluation of the method is needed.

  • 250. Order onlineBuy this publication >>
    Gu, Xuan
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Advanced analysis of diffusion MRI data2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Diffusion magnetic resonance imaging (diffusion MRI) is a non-invasive imaging modality which can measure diffusion of water molecules, by making the MRI acquisition sensitive to diffusion. Diffusion MRI provides unique possibilities to study structural connectivity of the human brain, e.g. how the white matter connects different parts of the brain. Diffusion MRI enables a range of tools that permit qualitative and quantitative assessments of many neurological disorders, such as stroke and Parkinson.

    This thesis introduces novel methods for diffusion MRI data analysis. Prior to estimating a diffusion model in each location (voxel) of the brain, the diffusion data needs to be preprocessed to correct for geometric distortions and head motion. A deep learning approach to synthesize diffusion scalar maps from a T1-weighted MR image is proposed, and it is shown that the distortion-free synthesized images can be used for distortion correction. An evaluation, involving both simulated data and real data, of six methods for susceptibility distortion correction is also presented in this thesis.

    A common problem in diffusion MRI is to estimate the uncertainty of a diffusion model. An empirical evaluation of tractography, a technique that permits reconstruction of white matter pathways in the human brain, is presented in this thesis. The evaluation is based on analyzing 32 diffusion datasets from a single healthy subject, to study how reliable tractography is. In most cases only a single dataset is available for each subject. This thesis presents methods based on frequentistic (bootstrap) as well as Bayesian inference, which can provide uncertainty estimates when only a single dataset is available. These uncertainty measures can then, for example, be used in a group analysis to downweight subjects with a higher uncertainty.

    List of papers
    1. Repeated Tractography of a Single Subject: How High Is the Variance?
    Open this publication in new window or tab >>Repeated Tractography of a Single Subject: How High Is the Variance?
    2017 (English)In: Modeling, Analysis, and Visualization of Anisotropy / [ed] Thomas Schultz, Evren Özarslan, Ingrid Hotz, Springer, 2017, p. 331-354Chapter in book (Other academic)
    Abstract [en]

    We have investigated the test-retest reliability of diffusion tractography, using 32 diffusion datasets from a single healthy subject. Preprocessing was carried out using functions in FSL (FMRIB Software Library), and tractography was carried out using FSL and Dipy. The tractography was performed in diffusion space, using two seed masks (corticospinal and cingulum gyrus tracts) created from the JHU White-Matter Tractography atlas. The tractography results were then warped into MNI standard space by a linear transformation. The reproducibility of tract metrics was examined using the standard deviation, the coefficient of variation (CV) and the Dice similarity coefficient (DSC), which all indicated a high reproducibility. Our results show that the multi-fiber model in FSL is able to reveal more connections between brain areas, compared to the single fiber model, and that distortion correction increases the reproducibility.

    Place, publisher, year, edition, pages
    Springer, 2017
    Series
    Mathematics and Visualization (MATHVISUAL), ISSN 1612-3786, E-ISSN 2197-666X
    National Category
    Medical Engineering
    Identifiers
    urn:nbn:se:liu:diva-142047 (URN)10.1007/978-3-319-61358-1_14 (DOI)978-3-319-61357-4 (ISBN)978-3-319-61358-1 (ISBN)
    Available from: 2017-10-19 Created: 2017-10-19 Last updated: 2019-11-19Bibliographically approved
    2. Bayesian Diffusion Tensor Estimation with Spatial Priors
    Open this publication in new window or tab >>Bayesian Diffusion Tensor Estimation with Spatial Priors
    Show others...
    2017 (English)In: CAIP 2017: Computer Analysis of Images and Patterns, 2017, Vol. 10424, p. 372-383Conference paper, Published paper (Refereed)
    Abstract [en]

    Spatial regularization is a technique that exploits the dependence between nearby regions to locally pool data, with the effect of reducing noise and implicitly smoothing the data. Most of the currently proposed methods are focused on minimizing a cost function, during which the regularization parameter must be tuned in order to find the optimal solution. We propose a fast Markov chain Monte Carlo (MCMC) method for diffusion tensor estimation, for both 2D and 3D priors data. The regularization parameter is jointly with the tensor using MCMC. We compare FA (fractional anisotropy) maps for various b-values using three diffusion tensor estimation methods: least-squares and MCMC with and without spatial priors. Coefficient of variation (CV) is calculated to measure the uncertainty of the FA maps calculated from the MCMC samples, and our results show that the MCMC algorithm with spatial priors provides a denoising effect and reduces the uncertainty of the MCMC samples.

    Series
    Lecture Notes in Computer Science, ISSN 0302-9743, E-ISSN 1611-3349 ; 10424
    Keywords
    Spatial regularization, Diffusion tensor, Spatial priors Markov chain, Monte Carlo Fractional anisotropy
    National Category
    Medical Engineering
    Identifiers
    urn:nbn:se:liu:diva-139844 (URN)10.1007/978-3-319-64689-3_30 (DOI)000432085900030 ()978-3-319-64689-3 (ISBN)978-3-319-64688-6 (ISBN)
    Conference
    International Conference on Computer Analysis of Images and Patterns
    Note

    Funding agencies: Information Technology for European Advancement (ITEA) 3 Project BENEFIT (better effectiveness and efficiency by measuring and modelling of interventional therapy); Swedish Research Council [2015-05356, 2013-5229]; National Institute of Dental and Craniof

    Available from: 2017-08-17 Created: 2017-08-17 Last updated: 2019-11-19
    3. Multi-fiber Estimation and Tractography for Diffusion MRI using mixture of Non-central Wishart Distributions
    Open this publication in new window or tab >>Multi-fiber Estimation and Tractography for Diffusion MRI using mixture of Non-central Wishart Distributions
    Show others...
    2017 (English)In: VCBM 17: Eurographics Workshop on Visual Computing for Biology and Medicine, The Eurographics Association , 2017, p. 1-5Conference paper, Published paper (Refereed)
    Abstract [en]

    Multi-compartmental models are popular to resolve intra-voxel fiber heterogeneity. One such model is the mixture of central Wishart distributions. In this paper, we use our recently proposed model to estimate the orientations of crossing fibers within a voxel based on mixture of non-central Wishart distributions. We present a thorough comparison of the results from other fiber reconstruction methods with this model. The comparative study includes experiments on a range of separation angles between crossing fibers, with different noise levels, and on real human brain diffusion MRI data. Furthermore, we present multi-fiber visualization results using tractography. Results on synthetic and real data as well as tractography visualization highlight the superior performance of the model specifically for small and middle ranges of separation angles among crossing fibers.

    Place, publisher, year, edition, pages
    The Eurographics Association, 2017
    Series
    Eurographics Workshop on Visual Computing for Biology and Medicine, ISSN 2070-5778, E-ISSN 2070-5786 ; 2017
    National Category
    Medical Engineering
    Identifiers
    urn:nbn:se:liu:diva-140739 (URN)10.2312/vcbm.20171244 (DOI)9783038680369 (ISBN)
    Conference
    Eurographics Workshop on Visual Computing for Biology and Medicine, September 7-8, 2017, Bremen, Germany
    Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2019-11-19Bibliographically approved
    4. Using the wild bootstrap to quantify uncertainty in mean apparent propagator MRI
    Open this publication in new window or tab >>Using the wild bootstrap to quantify uncertainty in mean apparent propagator MRI
    2019 (English)In: Frontiers in Neuroinformatics, ISSN 1662-5196, E-ISSN 1662-5196, Vol. 13, article id 43Article in journal (Refereed) Published
    Abstract [en]

    Purpose: Estimation of uncertainty of MAP-MRI metricsis an important topic, for several reasons. Bootstrap deriveduncertainty, such as the standard deviation, providesvaluable information, and can be incorporated in MAP-MRIstudies to provide more extensive insight.

    Methods: In this paper, the uncertainty of different MAPMRImetrics was quantified by estimating the empirical distributionsusing the wild bootstrap. We applied the wildbootstrap to both phantom data and human brain data, andobtain empirical distributions for theMAP-MRImetrics returnto-origin probability (RTOP), non-Gaussianity (NG) and propagatoranisotropy (PA).

    Results: We demonstrated the impact of diffusion acquisitionscheme (number of shells and number of measurementsper shell) on the uncertainty of MAP-MRI metrics.We demonstrated how the uncertainty of these metrics canbe used to improve group analyses, and to compare differentpreprocessing pipelines. We demonstrated that withuncertainty considered, the results for a group analysis canbe different.

    Conclusion: Bootstrap derived uncertain measures provideadditional information to the MAP-MRI derived metrics, andshould be incorporated in ongoing and future MAP-MRIstudies to provide more extensive insight.

    Place, publisher, year, edition, pages
    Frontiers Media S.A., 2019
    Keywords
    Bootstrap, diffusion MRI, MAP-MRI, uncertainty, RtoP, NG, PA
    National Category
    Medical Engineering
    Identifiers
    urn:nbn:se:liu:diva-157089 (URN)10.3389/fninf.2019.00043 (DOI)000471589200001 ()31244637 (PubMedID)
    Note

    Funding agencies:  Swedish Research Council [2015-05356]; Linkoping University Center for Industrial Information Technology (CENIIT); Knut and Alice Wallenberg Foundation project Seeing Organ Function; National Institute of Dental and Craniofacial Research (NIDCR); National

    Available from: 2019-05-27 Created: 2019-05-27 Last updated: 2019-11-19
    5. Generating Diffusion MRI Scalar Maps from T1 Weighted Images Using Generative Adversarial Networks
    Open this publication in new window or tab >>Generating Diffusion MRI Scalar Maps from T1 Weighted Images Using Generative Adversarial Networks
    2019 (English)In: Image Analysis: Lecture Notes in Computer Science / [ed] Felsberg M., Forssén PE., Sintorn IM., Unger J., Springer Publishing Company, 2019, p. 489-498Conference paper, Published paper (Refereed)
    Abstract [en]

    Diffusion magnetic resonance imaging (diffusion MRI) is a non-invasive microstructure assessment technique. Scalar measures, such as FA (fractional anisotropy) and MD (mean diffusivity), quantifying micro-structural tissue properties can be obtained using diffusion models and data processing pipelines. However, it is costly and time consuming to collect high quality diffusion data. Here, we therefore demonstrate how Generative Adversarial Networks (GANs) can be used to generate synthetic diffusion scalar measures from structural T1-weighted images in a single optimized step. Specifically, we train the popular CycleGAN model to learn to map a T1 image to FA or MD, and vice versa. As an application, we show that synthetic FA images can be used as a target for non-linear registration, to correct for geometric distortions common in diffusion MRI.

    Place, publisher, year, edition, pages
    Springer Publishing Company, 2019
    Series
    Lecture Notes in Computer Science, ISSN 0302-9743, E-ISSN 1611-3349
    Keywords
    Diffusion MRI, Generative Adversarial Networks, CycleGAN, Distortion correction
    National Category
    Medical Engineering
    Identifiers
    urn:nbn:se:liu:diva-158662 (URN)10.1007/978-3-030-20205-7_40 (DOI)978-3-030-20204-0 (ISBN)978-3-030-20205-7 (ISBN)
    Conference
    Scandinavian Conference on Image Analysis, SCIA
    Available from: 2019-07-08 Created: 2019-07-08 Last updated: 2019-11-19
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