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  • 1.
    Antonsson, Johan
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Eriksson, Ola
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Blomstedt, Patric
    Department of Neurosurgery, University Hospital, Umeå, Sweden.
    Bergenheim, Tommy
    Department of Neurosurgery, University Hospital, Umeå, Sweden.
    Hariz, Marwan
    Department of Neurosurgery, University Hospital, Umeå, Sweden.
    Richter, Johan
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Diffuse reflectance spectroscopy measurements for tissue type discrimination during deep brain stimulation2008In: Journal of neural engineering, ISSN 1741-2560, Vol. 5, no 2, p. 185-190Article in journal (Refereed)
    Abstract [en]

    Diffuse reflectance spectroscopy as a method for improving intracerebral guidance during functional neurosurgery has been investigated. An optical probe was developed for measurements during stereotactic and functional neurosurgery in man. The aim of the study was to investigate the spectral differences between white and grey matter and between white matter and functional targets. Diffuse reflectance spectroscopy measurements in ten patients were recorded at incremental steps towards and in three different functional targets (STN, GPi and Zi). The recorded spectra along the trajectory were sorted into white or grey matter, based on preoperative MRI images or the recorded spectral shape and intensity. The difference between tissue types was calculated as a quotient. Significant intensity differences between white and grey matter were found to be at least 14% (p < 0.05) and 20% (p < 0.0001) for MRI and spectral-sorted data respectively. The reflectance difference between white matter and the functional targets of GPi was higher than for STN and Zi. The results indicate that diffuse reflectance spectroscopy has a potential to be developed to a suitable complement to other intracerebral guidance methods.

  • 2.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Milos, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Fluorescence spectroscopy and optical coherence tomography for brain tumor detection2016Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. Recently, neurosurgical microscopes have been modified to incorporate fluorescence modules for detection of tumor when 5-aminolevulinic acid (5-ALA) is used as a contrast. We have in combination with the fluorescence microscopes implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid (ALA) induced protoporphyrin IX (PpIX) in the gliomas in 50 patients intraoperatively. The results show a significantly high sensitivity for differentiating tumor from the healthy tissue and distinguished fluorescence intensity levels in the tumor cell infiltration zone around the tumor. However, knowledge on association of the quantified fluorescence signals specifically in the intermediate inflammatory zone with the infiltrative tumor cells can be complemented with volumetric tissue imaging and a higher precision histopathological analysis. In this work, a spectral domain optical coherence tomography (OCT) system with central wavelength of 1325nm has been used to image the tissue volume that the fluorescence is collected from and is evaluated against histopathological analysis for a higher precision slicing. The results show that although healthy brain has a homogenous microstructure in the OCT images, the brain tumor shows a distinguished texture in the images correlated with the PpIX fluorescence intensity and histopathology.

  • 3.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Milos, Peter
    Region Östergötland, Center for Surgery, Orthopaedics and Cancer Treatment, Department of Surgery in Linköping.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hildesjö, Camilla
    Linköping University, Department of Clinical and Experimental Medicine, Division of Clinical Sciences. Linköping University, Faculty of Medicine and Health Sciences.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering.
    Detection of brain tumor using fluorescence and optical coherence tomography2015Conference paper (Refereed)
    Abstract [en]

    Resection of brain tumor is a challenging task as the tumor does not have clear borders and the malignant types specifically have often a diffuse and infiltrative pattern of growth. We have previously implemented and evaluated a fluorescence spectroscopy based handheld probe for detecting the 5-aminolevulinic acid induced protoporphyrin IX (PpIX) in the gliomas. To add another dimension to the brain tumor detection and volumetric analysis of the tissue that exhibits fluorescence, optical coherence tomography was investigated on tumor specimens.

    Material and Methods:

    A fluorescence microscopy and a spectroscopy system as reported previously were used for detecting the fluorescence signals [1, 2]. A total of 50 patients have been included for intraoperative assessment of the tumor borders using the fluorescence techniques. A spectral domain OCT imaging system (TELESTO II, Thorlabs, Inc., NJ, USA) with central wavelength of 1325 nm was used to study the tissue microstructure post operatively. The system has a resolution of 13 and 5.5 μm in the lateral and axial directions, respectively. Tissue specimens from three patients undergoing brain tumor surgery were studied using the OCT system.

    Results and Conclusion:

    Using fluorescence spectroscopy the tumor could be detected with a sensitivity of 0.84 which was significantly higher than that of the surgical microscope (0.30). Brain tissue appeared rather homogeneous in the OCT images however the highly malignant tissue showed a clear structural difference from the non-malignant or low malignant brain tumor tissue which could be related to the fluorescence signal intensities.

  • 4.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Andersson-Engel, Stefan
    Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence guided resection of glioblastoma multiforme using an optical touch pointer-Clinical evaluation2010Conference paper (Refereed)
  • 5.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Department of Physics, Lund University.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fiber optic based fluorescence guided cerebral glioma resection using a pulsed laser setup2008Conference paper (Refereed)
  • 6.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Linköping University, The Institute of Technology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Optical Touch Pointer for Fluorescence Guided Glioblastoma Resection Using 5-Aminolevulinic Acid2010In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 42, no 1, p. 9-14Article in journal (Refereed)
    Abstract [en]

    Background and Objective

    Total tumor resection in patients with glioblastoma multiforme (GBM) is difficult to achieve due to the tumor's infiltrative way of growing and morphological similarity to the surrounding functioning brain tissue. The diagnosis is usually subjectively performed using a surgical microscope. The objective of this study was to develop and evaluate a hand-held optical touch pointer using a fluorescence spectroscopy system to quantitatively distinguish healthy from malignant brain tissue intraoperatively.

    Study Design/Materials and Methods

    A fluorescence spectroscopy system with pulsed modulation was designed considering optimum energy delivery to the tissue, minimal photobleaching of PpIX and omission of the ambient light background in the operating room (OR). 5-Aminolevulinic acid (5-ALA) of 5 mg/kg body weight was given to the patients with a presumed GBM prior to surgery. During the surgery a laser pulse at 405 nm was delivered to the tissue. PpIX in glioblastoma tumor cells assigned with peaks at 635 and 704 nm was detected using a fiber optical probe.

    Results/Conclusion

    By using the pulsed fluorescence spectroscopy, PpIX fluorescence is quantitatively detected in the GBM. An effective suppression of low power lamp background from the recorded spectra in addition to a significant reduction of high power surgical lights is achieved.

  • 7.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery.
    Andersson-Engels, Stefan
    Dept. of Physics, Lund University, Lund, Sweden.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Photobleaching behavior of protoporphyrin IX during 5-aminolevulinic acid marked glioblastoma detection2009In: Photonic Therapeutics and Diagnostics V / [ed] Nikiforos Kollias; Bernard Choi; Haishan Zeng; Reza S. Malek; Brian J. Wong; Justus F. R. Ilgner; Kenton W. Gregory; Guillermo J. Tearney; Laura Marcu; Henry Hirschberg; Steen J. Madsen, SPIE - International Society for Optical Engineering, 2009, p. 716131-1-716131-8Conference paper (Other academic)
    Abstract [en]

    The highly malignant brain tumor, glioblastoma multiforme (GBM), is difficult to fully delineate during surgical resection due to its infiltrative ingrowth and morphological similarities to surrounding functioning brain tissue. Selectiveness of GBM to 5-aminolevulinic acid (5-ALA) induced protoporphyrin IX (PpIX) is reported by other researchers to visualize tumor margins under blue light microscopy. To allow objective detection of GBM, a compact and portable fiber optic based fluorescence spectroscopy system is developed. This system is able to deliver excitation laser light (405 nm) in both the continuous and pulsed mode. PpIX fluorescence peaks are detected at 635 and 704 nm, using a fiber-coupled spectrometer. It is necessary to optimize the detection efficiency of the system as the PpIX quickly photobleaches during the laser illumination. A light dose of 2.5 mJ (fluence rate = 9 mJ/mm2) is experimentally approved to excite an acceptable level of fluourescence signal arising from glioblastoma. In pulsed illumination mode, an excitation dose of 2.5 mJ, with a dark interval of 0.5 s (duty cycle 50%) shows a significantly shorter photobleaching time in comparison to the continuous illumination mode with the same laser power (p < 0.05). To avoid photobleaching (the remaining signal is more than 90% of its initial value) when measuring with 2.5 mJ delivered energy, the time for continuous and pulsed illumination should be restricted to 2.5 and 1.1 s, respectively.

  • 8.
    Haj-Hosseini, Neda
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery2015In: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 12, no 2, p. 209-214Article in journal (Refereed)
    Abstract [en]

    Background

    Using 5-aminolevulinic acid (ALA) as an intraoperative fluorescence contrast has been proven to improve the resection of glioblastoma and contribute to prolonged patient survival. ALA accumulates as protoporphyrin IX (PpIX) in the tumor cells and is administered in an advised dose of 20 mg/kg body weight (b.w.) for brain tumor resection using fluorescence surgical microscopes. PpIX fluorescence availability and intensities of a four folds lower ALA dose (5 mg/kg b.w.) has been investigated in glioblastomas and skin using a spectroscopy system adapted for surgical guidance.

    Methods

    A total of 30 adult patients diagnosed with high grade gliomas were included in the analysis. ALA was orally administered in doses of 5 mg/kg b.w. (n = 15) dissolved in orange juice or 20 mg/kg b.w. (n = 15) dissolved in water. A fluorescence spectroscopy system with a handheld fiber-optical probe was used for performing the quantitative fluorescence measurements.

    Results

    The binominal comparison of the diagnostic performance parameters showed no significant statistical difference (p > 0.05). The median fluorescence values in tumor were 2-3 times higher for the high ALA dose group. No PpIX was detected in the skin of the patients in the low dose group (0/4) while PpIX was detected in the skin of the majority of the patients in the high ALA dose group (13/14).

    Conclusions

    Application of 5 mg/kg ALA was evaluated as equally reliable as the higher dose regarding the diagnostic performance when guidance was performed using a spectroscopic system. Moreover, no PpIX was detected in the skin of the patients.

  • 9.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Milos, Peter
    Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Neurokirurgi.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Center for Diagnostics, Clinical pathology.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy2018In: Biomedical Optics Express, E-ISSN 2156-7085, Vol. 9, no 5, p. 2284-2296Article in journal (Refereed)
    Abstract [en]

    A fiber optic probe was developed for guidance during stereotactic brain biopsy procedures to target tumor tissue and reduce the risk of hemorrhage. The probe was connected to a setup for the measurement of 5-aminolevulinic acid (5-ALA) induced fluorescence and microvascular blood flow. Along three stereotactic trajectories, fluorescence (n = 109) and laser Doppler flowmetry (LDF) (n = 144) measurements were done in millimeter increments. The recorded signals were compared to histopathology and radiology images. The median ratio of protoporphyrin IX (PpIX) fluorescence and autofluorescence (AF) in the tumor was considerably higher than the marginal zone (17.3 vs 0.9). The blood flow showed two high spots (3%) in total. The proposed setup allows simultaneous and real-time detection of tumor tissue and microvascular blood flow for tracking the vessels.

  • 10.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Olivecrona, Magnus
    Department of Neurosurgery, Umeå University.
    Hillman, Jan
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hallbeck, Martin
    Linköping University, Department of Clinical and Experimental Medicine, Experimental Pathology. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Center for Diagnostics, Department of Clinical Pathology and Clinical Genetics.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence guided spectroscopy versus fluorescence microscopy for brain tumor resection2013Conference paper (Other academic)
  • 11.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence spectroscopy for ALA-guided glioblastoma resection using a fiber-optical probe2012Conference paper (Refereed)
  • 12.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Medicine and Health Sciences.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Medicine and Health Sciences.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Photodiagnostics in Brain Tumor Surgery2014In: Medicinteknikdagarna, Göteborg, 14-16 oktober, 2014: Sammanfattningar, Göteborg: Svensk förening för medicinsk teknik och fysik , 2014Conference paper (Refereed)
    Abstract [en]

    Since getting approved for clinical application in neurosurgery 5-aminolevulinic acid (ALA), that is a fluorescence contrast agent, has attracted the interest of many neurosurgical clinics to implement it in their surgical routine. ALA naturally exists in the body and the external administration of the substance induces accumulation of a fluorophore known as protoporphyrin IX (PpIX) in the malignant cells due to a broken blood brain barrier and the altered enzyme levels in the brain tumor. The detection and visualization of PpIX in the clinical routine is conventionally performed using a modified neuro surgical microscope. As a complementary technique for detection of ALA-induced fluorescence and to perform objective and quantitative measurements, our group has developed a spectroscopy system adapted to the equipment in the operating room. The system includes a hand-held fiber optic probe which can be integrated in the neuronavigation and stereotactic systems. The main advantages of the system are the ease of use, high sensitivity, quantitative fluorescence detection and the possibility of applying a low dose of fluorescence contrast agent while obtaining equally reliable results as with the high dose. In this contribution we present our experience, gains and challenges from implementation of the system during brain tumor surgery in forty adult patients. The methods and systems are currently being adapted for implementation during operations of pediatric brain tumors.

  • 13.
    Haj-Hosseini, Neda
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Health Sciences.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Quantitative ALA photodiagnostics in Neurosurgery2014Conference paper (Other academic)
  • 14.
    Hemm, Simone
    et al.
    Institute for Medical and Analytical Technologies (IMA), FHNW, Switzerland.
    Richter, Johan C.O.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Optical measurements for guidance during deep brain stimulation implantation2011Conference paper (Refereed)
  • 15.
    Ilias, Michail
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Westermark, Frida
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Brantmark, Martin
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Department of Physics, Lund Institute of Technology, Lund, Sweden.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Evaluation of a Fiber-Optic Fluorescence Spectroscopy System to Assist Neurosurgical Tumor Resections2007In: Novel Optical Instrumentation for Biomedical Applications III (Proceedings Volume) / [ed] Christian D. Depeursinge, Bellingham, Washington, USA: SPIE - International Society for Optical Engineering, 2007, Vol. 6631, p. 66310W-1-66310W-8Conference paper (Other academic)
    Abstract [en]

    The highly malignant brain tumor, glioblastoma multiforme, is difficult to totally resect without aid due to its infiltrative way of growing and its morphological similarities to surrounding functioning brain under direct vision in the operating field. The need for an inexpensive and robust real-time visualizing system for resection guiding in neurosurgery has been formulated by research groups all over the world. The main goal is to develop a system that helps the neurosurgeon to make decisions during the surgical procedure. A compact fiber optic system using fluorescence spectroscopy has been developed for guiding neurosurgical resections. The system is based on a high power light emitting diode at 395 nm and a spectrometer. A fiber bundle arrangement is used to guide the excitation light and fluorescence light between the instrument and the tissue target. The system is controlled through a computer interface and software package especially developed for the application. This robust and simple instrument has been evaluated in vivo both on healthy skin but also during a neurosurgical resection procedure. Before surgery the patient received orally a low dose of 5-aminolevulinic acid, converted to the fluorescence tumor marker protoporphyrin IX in the malignant cells. Preliminary results indicate that PpIX fluorescence and brain tissue autofluorescence can be recorded with the help of the developed system intraoperatively during resection of glioblastoma multiforme.

  • 16.
    Ilias, Michail
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Richter, Johan
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Wårdell, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Andersson-Engels, Stefan
    Inst för fysik Lunds tekniska högskola.
    Ett optiskt instrument för intraoperativ registrering av fluorescensspektra vid resektion av hjärntumörer - Ett framtida beslutsstödssystem för kirurgen?2007In: Medicinteknikdagarna,2007, 2007Conference paper (Other academic)
  • 17.
    Richter, Johan C.O.
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Haj-Hosseini, Neda
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Department of Physics, Lund University.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence Spectroscopy Measurements in Ultrasonic Navigated Resection of Malignant Brain Tumors2011In: Lasers in Surgery and Medicine, ISSN 0196-8092, E-ISSN 1096-9101, Vol. 43, no 1, p. 8-14Article in journal (Refereed)
    Abstract [en]

    Background and Objective: Glioblastoma multiforme is a highly malignant primary brain tumor. It has no border but at best a marginal zone, however, invisible to the surgeon. An optical touch pointer (OTP) enabling differentiation of healthy and tumor tissue by means of fiber-optic fluorescence spectroscopy has been developed. In combination with an ultrasonic navigation system, the OTP may be used for demarcation of resectable tumor tissue. The aim of the study was to evaluate the clinical performance of OTP during surgery of malignant brain tumors. 

    Study Design/Materials and Methods: Nine patients were operated on with the standard surgical procedure, including white light microscopy and navigation. A total of 5 mg/kg bodyweight of 5-amino-levulin acid was orally administrated before surgery. The OTP was calibrated into the ultrasound-based navigation system and measurements were performed in tumor core and along the tumor border. The ratio between the protoporphyrin IX fluorescence at 635 nm and the autofluorescence was used for quantifications of data. Biopsies (n =20), ultrasound images (n = 30), and visual inspection (n =180) were compared to the fluorescence ratio. 

    Results/Conclusion : Healthy and tumor tissue could be identified and differentiated with the OTP(P < 0.001). The fluorescence ratio in average was 0 outside the tumor and low in the gliotic edema zone around the tumor. It increased in the marginal zone and was highest in the solid tumor tissue. In the necrotic tissue, in the center of the tumor, the ratio in average was 0. The OTP can be used in combination with ultrasound-based navigation and may help to determine whether to resect otherwise not identifiable tissue.

  • 18.
    Richter, Johan C.O.
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Haj-Hosseini, Neda
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence Spectroscopy based identification of Glioblastoma multiforme2011Conference paper (Refereed)
  • 19.
    Richter, Johan
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Haj-Hosseini, Neda
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Fluorescence guided brain tumour resection2014Conference paper (Other academic)
  • 20.
    Richter, Johan
    et al.
    Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Haj-Hosseini, Neda
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Andersson-Engels, Stefan
    Department of Physics, Lund University, Sweden.
    Wårdell, Karin
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Tumor resection with fiber-optic fluorescence spectroscopy system, ultrasound based neuronavigation and peroperative CT-scan2008In: XVIII Congress of the European Society for Stereotactic and Functional Neurosurgery,2008, 2008Conference paper (Other academic)
  • 21.
    Wårdell, Karin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Blomstedt, P.
    Department of Neurosurgery, University Hospital, Umeå, Sweden.
    Richter, Johan
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Antonsson, Johan
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Eriksson, Ola
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Zsigmond, Peter
    Linköping University, Faculty of Health Sciences. Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Östergötlands Läns Landsting, Reconstruction Centre, Department of Neurosurgery UHL.
    Bergenheim, A.T.
    Department of Neurosurgery, University Hospital, Umeå, Sweden.
    Hariz, M.I.
    Department of Neurosurgery, University Hospital, Umeå, Sweden, Institute of Neurology, University College London, London, United Kingdom.
    Intracerebral microvascular measurements during deep brain stimulation implantation using laser doppler perfusion monitoring2007In: Stereotactic and Functional Neurosurgery, ISSN 1011-6125, E-ISSN 1423-0372, Vol. 85, no 6, p. 279-286Article in journal (Refereed)
    Abstract [en]

    The aim of the study was to investigate if laser Doppler perfusion monitoring (LDPM) can be used in order to differentiate between gray and white matter and to what extent microvascular perfusion can be recorded in the deep brain structures during stereotactic neurosurgery. An optical probe constructed to fit in the Leksell® Stereotactic System was used for measurements along the trajectory and in the targets (globus pallidus internus, subthalamic nucleus, zona incerta, thalamus) during the implantation of deep brain stimulation leads (n = 22). The total backscattered light intensity (TLI) reflecting the grayness of the tissue, and the microvascular perfusion were captured at 128 sites. Heartbeat-synchronized pulsations were found at all perfusion recordings. In 6 sites the perfusion was more than 6 times higher than the closest neighbor indicating a possible small vessel structure. TLI was significantly higher (p < 0.005) and the perfusion significantly lower (p < 0.005) in positions identified as white matter in the respective MRI batch. The measurements imply that LDPM has the potential to be used as an intracerebral guidance tool.

  • 22.
    Wårdell, Karin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Johansson, Johannes
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Blomstedt, Patric
    Dept of Neurosurgery, Umeå University Hospital, Sweden.
    Optical measurements for guidance during deep brain stimulation surgery2009In: World Congress on Medical Physics and Biomedical Engineering / [ed] Olaf Dössel and Wolfgang C. Schlegel, Berlin/Heidelberg: Springer , 2009, p. 516-517Conference paper (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease and related movement disorders. The success of DBS is highly dependent on electrode location, electrical parameter settings and the surgical procedure. In this paper an overview of the current status of optical measurements for intracerebral guidance performed during DBS implantation is presented. Laser Doppler perfusion monitoring and/or reflection spectroscopy measurements have been done in relation to more than 70 DBS lead implantations to wards targets in the deep brain structures. The techniques have also been compared with impedance monitoring, and simulation of the measurement depth has been done with Monte Carlo technique. These studies show that grey-white matter boundaries can be determined with a resolution higher than for both impedance measurements and magnetic resonance imaging.

  • 23.
    Wårdell, Karin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Linköping University, Center for Medical Image Science and Visualization (CMIV).
    Rejmstad, Peter
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Hemm-Ode, Simone
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Institute for Medical and Analytical Technologies, University of Applied Sciences and Art Northwestern Switzerland, Basel.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuroscience. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Microvascular Blood Flow in the Deep Brain Structures - Laser Doppler Measurements during DBS-implantations2014In: Movement Disorders 2014, Volym 29, Suppl 1 :1271, 2014Conference paper (Other academic)
  • 24.
    Wårdell, Karin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan C.O.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hemm, Simone
    Institute for Medical and Analytical Technologies, University of Applied Sciences, Northwestern Switzerland.
    Optical measurements for guidance during deep brain stimulation implantation2011Conference paper (Refereed)
  • 25.
    Wårdell, Karin
    et al.
    Linköping University, Department of Biomedical Engineering, Division of Biomedical Engineering. Linköping University, Faculty of Science & Engineering.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Division of Neuro and Inflammation Science. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences. Region Östergötland, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hemm, Simone
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Science & Engineering. Institute for Medical and Analytical Technologies, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
    Optical Guidance System for Deep Brain Stimulation Surgery: from Experimental Studies to Clinical Use2018In: , Hollywood, Florida, United States, 2018, article id CTh2B.3Conference paper (Refereed)
    Abstract [en]

    Laser Doppler flowmetry (LDF) has been adapted for optical guidance during stereotactic deep brain stimulation (DBS) surgery. It has been used in more than 130 DBS implantations. The necessary steps to go from experimental studies to clinical use in the neurosurgical setting are reviewed.

  • 26.
    Wårdell, Karin
    et al.
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Hemm, Simone
    University of Applied Sciences Northwestern Switzerland .
    Optical Measurements for Guidance during Deep Brain Stimulation Implantation2012Conference paper (Refereed)
    Abstract [en]

    Deep brain stimulation (DBS) is an established treatment for Parkinson’s disease and related movement disorders. The success of DBS is highly dependent on electrode location, electrical parameter settings and the surgical procedure. In this paper an overview of the current status of optical measurements for intracerebral guidance performed during DBS implantation is presented. Laser Doppler perfusion monitoring and/or reflection spectroscopy measurements have been done in relation to more than 70 DBS lead implantations to wards targets in the deep brain structures. The techniques have also been compared with impedance monitoring, and simulation of the measurement depth has been done with Monte Carlo technique. These studies show that grey-white matter boundaries can be determined with a resolution higher than for both impedance measurements and magnetic resonance imaging.

  • 27.
    Wårdell, Karin
    et al.
    Linköping University, The Institute of Technology. Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation.
    Zsigmond, Peter
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Richter, Johan
    Linköping University, Department of Clinical and Experimental Medicine, Neurosurgery. Linköping University, Faculty of Health Sciences.
    Hemm, Simone
    University of Applied Sciences Northwestern Switzerland, Institute for Medical and Analytical Technologies, Muttenz, Switzerland..
    Relationship Between Laser Doppler Signals and Anatomy During Deep Brain Stimulation Electrode Implantation Toward the Ventral Intermediate Nucleus and Subthalamic Nucleus2013In: Neurosurgery, ISSN 0148-396X, E-ISSN 1524-4040, Vol. 72, no 2, p. 127-140Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Deep brain stimulation (DBS) requires precise and safe navigation to the chosen target. Optical measurements allow monitoring of gray-white tissue boundaries (total light intensity [TLI]) and microvascular blood flow during stereotactic procedures.

    OBJECTIVE: To establish the link between TLI/blood flow and anatomy along trajectories toward the ventral intermediate nucleus (Vim) and subthalamic nucleus (STN).

    METHODS: Stereotactic laser Doppler measurements were obtained with millimeter precision from the cortex toward the Vim (n = 13) and STN (n = 9). Optical trajectories of TLI and blood flow were created and compared with anatomy by superimposing the Schaltenbrandt-Wahren atlas on the patients' pre- and postoperative images. Measurements were divided into anatomic subgroups and compared statistically.

    RESULTS: Typical TLI trajectories with well-defined anatomic regions could be identified for the Vim and STN. TLI was significantly lower (P < .001) and microvascular blood flow significantly higher (P = .01) in the Vim targets. Of 1285 sites, 38 showed blood flow peaks, 27 of them along the Vim trajectories. High blood flow was more common close to the sulci and in the vicinity of the caudate/putamen. Along 1 Vim trajectory, a slight bleeding was suspected during insertion of the probe and confirmed with postoperative computed tomography.

    CONCLUSION: Laser Doppler is useful for intraoperative guidance during DBS implantation because simultaneous measurement of tissue grayness and microvascular blood flow can be done along the trajectory with millimeter precision. Typical but different TLI trajectories were found for the Vim and STN.

  • 28.
    Xie, Haiyan
    et al.
    Dept. of Physics, Lund University, Sweden.
    Haj-Hosseini, Neda
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Richter, Johan
    Linköping University, Department of Biomedical Engineering. Linköping University, The Institute of Technology. Östergötlands Läns Landsting, Anaesthetics, Operations and Specialty Surgery Center, Department of Neurosurgery.
    Wårdell, Karin
    Linköping University, Department of Biomedical Engineering, Biomedical Instrumentation. Linköping University, The Institute of Technology.
    Andersson-Engels, Stefan
    Dept. of Physics, Lund University, Sweden.
    Fluorescence spectroscopy for guiding malignant brain tumour resection with Optical Touch Pointer2010Conference paper (Refereed)
    Abstract [en]

    Glioblastoma multiforme (GBM), a highly malignant primary brain tumor, is difficult to distinguish from from its surrounding functioning tissue under direct vision in the operating field, since it grows in an infiltrative growth pattern. The main challenge in the surgical treatment of GBM is to fully resect the tumor and avoid neurological impairment. In this paper we extend previous proof-of-principle studies by extending the clinical potential of OTP with the introduction of more sophisticated multivariate analysis schemes. The aim is to distinguish tumor and healthy tissue as well as possible using singular value decomposition (SVD) and cluster analysis methods.

1 - 28 of 28
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