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Haj-Hosseini, N., Richter, J., Milos, P., Hallbeck, M. & Wårdell, K. (2018). 5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy. Biomedical Optics Express, 9(5), 2284-2296
Open this publication in new window or tab >>5-ALA fluorescence and laser Doppler flowmetry for guidance in a stereotactic brain tumor biopsy
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2018 (English)In: Biomedical Optics Express, E-ISSN 2156-7085, Vol. 9, no 5, p. 2284-2296Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Optical Society of America, 2018
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-147514 (URN)10.1364/BOE.9.002284 (DOI)000431181700022 ()29760987 (PubMedID)
Funder
Swedish Childhood Cancer Foundation, 2013-0043Linköpings universitet, LiU CancerRegion Östergötland, ALF LIO-599651
Note

Funding agencies: Linkoping University Cancer Organization; Swedish Childhood Cancer Organization [MT 2013-0043]; ALF Grants Region Ostergotland [LIO-599651]

Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2019-05-01Bibliographically approved
Haj-Hosseini, N., Richter, J., Hallbeck, M., Milos, P. & Wårdell, K. (2018). Stereotactic Brain Tumor Optical Biopsy. In: : . Paper presented at World Conference on Medical Physics and Biomedical Engineering (IUPESM,Prague, Czeck Republic, June 3-8 2018. Prague
Open this publication in new window or tab >>Stereotactic Brain Tumor Optical Biopsy
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2018 (English)Conference paper, Oral presentation with published abstract (Other academic)
Abstract [en]

To provide guidance for targeting diagnostic tumor tissue and to avoid vessel rupture during the biopsy procedure an application specific fiber optic probe was devel-oped. The setup incorporated an in-house developed fluorescence spectroscopy system for 5-aminolevulinic acid (5-ALA) induced protopophyrin IX (PpIX) for detection in the tumor, and laser Doppler flowmeter (LDF) system for measurement of blood perfusion. Fluorescence and blood flow were recorded millimeter-wise towards the pre-calculated target. In conclusion, the optical probe made real-time detection of tumor possible and has a potential for vessel detection during the biopsy procedures. Moreover, the PpIX fluorescence, autofluorescence and blood flow in the tumor could be studied at precise positions in the brain and the tumor. In the next step, further anal-ysis will be added.

Place, publisher, year, edition, pages
Prague: , 2018
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-145220 (URN)
Conference
World Conference on Medical Physics and Biomedical Engineering (IUPESM,Prague, Czeck Republic, June 3-8 2018
Funder
Swedish Childhood Cancer Foundation, MT 2013-0043
Available from: 2018-02-19 Created: 2018-02-19 Last updated: 2019-08-06Bibliographically approved
Rejmstad, P., Johansson, J. D., Haj-Hosseini, N. & Wårdell, K. (2017). A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy. Journal of Biophotonics, 10(3), 446-455
Open this publication in new window or tab >>A method for monitoring of oxygen saturation changes in brain tissue using diffuse reflectance spectroscopy
2017 (English)In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 10, no 3, p. 446-455Article in journal (Refereed) Published
Abstract [en]

Continuous measurement of local brain oxygen saturation (SO2) can be used to monitor the status of brain trauma patients in the neurocritical care unit. Currently, micro-oxygen-electrodes are considered as the “gold standard” in measuring cerebral oxygen pressure (pO2), which is closely related to SO2 through the oxygen dissociation curve (ODC) of hemoglobin, but with the drawback of slow in response time. The present study suggests estimation of SO2 in brain tissue using diffuse reflectance spectroscopy (DRS) for finding an analytical relation between measured spectra and the SO2 for different blood concentrations. The P3 diffusion approximation is used to generate a set of spectra simulating brain tissue for various levels of blood concentrations in order to estimate SO2. The algorithm is evaluated on optical phantoms mimicking white brain matter (blood volume of 0.5–2%) where pO2 and temperature is controlled and on clinical data collected during brain surgery. The suggested method is capable of estimating the blood fraction and oxygen saturation changes from the spectroscopic signal and the hemoglobin absorption profile.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2017
Keywords
oxygenation, diffuse reflectance spectroscopy, hemoglobin, optical phantom, human brain
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-127362 (URN)10.1002/jbio.201500334 (DOI)000398216200012 ()27094015 (PubMedID)
Note

Funding agencies: Swedish Childhood Cancer Foundation; Swedish Research Council [621-2010-4216, 621-2013-6078]

Available from: 2016-04-22 Created: 2016-04-22 Last updated: 2017-04-20Bibliographically approved
Haj-Hosseini, N., Gimm, O., Höög, A. & Johansson, K. (2017). Optiska metoder för identifiering av bisköldkörtel och sköldkörtel. In: : . Paper presented at Kirurgveckan, Jönköping, Sweden, Augusti 21-25, 2017. Jönköping, Sweden
Open this publication in new window or tab >>Optiska metoder för identifiering av bisköldkörtel och sköldkörtel
2017 (Swedish)Conference paper, Oral presentation with published abstract (Refereed)
Abstract [sv]

Identifiering av bisköldkörtlar är viktigt vid sköldkörtel- och bisköldkörtelkirurgi och kan vara svårt då de liknar omgivande vävnad såsom fett och lymfkörtlar. Peroperativ detektering av dessa vävnader kan förbättra möjligheten att bota patienter med hyperparathyroidism och minska risken för bisköldkörtelskador vid thyroideakirurgi. Optiska metoder är potentiella tekniker för att möjliggöra detta. Optiska tekniker utvärderades på vävnadsprover från patienter vid bisköldkörtel- och sköldkörteloperation. Teknikerna bestod av nära infraröd fluorescens (NIR) spektroskopi och optisk koherenstomografi (OCT) som ger en bild av vävnadens mikrostruktur liknande till ultraljud med högre upplösning (10 μm).

Place, publisher, year, edition, pages
Jönköping, Sweden: , 2017
Keywords
sköldkörtel, bisköldkörtel, kirurgi, optiska metoder, optisk koherenstomografi, fluorescens
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-140898 (URN)
Conference
Kirurgveckan, Jönköping, Sweden, Augusti 21-25, 2017
Available from: 2017-09-14 Created: 2017-09-14 Last updated: 2018-04-25Bibliographically approved
Markwardt, N., Haj-Hosseini, N., Hollnburger, B., Stepp, H., Zelenkov, P. & Rühm, A. (2016). 405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence-guided stereotactic biopsy of brain tumors. Journal of Biophotonics, 9(9), 901-912
Open this publication in new window or tab >>405 nm versus 633 nm for protoporphyrin IX excitation in fluorescence-guided stereotactic biopsy of brain tumors
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2016 (English)In: Journal of Biophotonics, ISSN 1864-063X, E-ISSN 1864-0648, Vol. 9, no 9, p. 901-912Article in journal (Refereed) Published
Abstract [en]

Fluorescence diagnosis may be used to improve the safety and reliability of stereotactic brain tumor biopsies using biopsy needles with integrated fiber optics. Based on 5-aminolevulinic-acid-induced protoporphyrin IX (PpIX) fluorescence, vital tumor tissue can be localized in vivo during the excision procedure to reduce the number of necessary samples for a reliable diagnosis. In this study, the practical suitability of two different PpIX excitation wavelengths (405 nm, 633 nm) was investigated on optical phantoms. Violet excitation at 405 nm provides a 50-fold higher sensitivity for the bulk tumor; this factor increases up to 100 with decreasing fluorescent volume as shown by ray tracing simulations. Red excitation at 633 nm, however, is noticeably superior with regard to blood layers obscuring the fluorescence. Experimental results on the signal attenuation through blood layers of well-defined thicknesses could be confirmed by ray tracing simulations. Typical interstitial fiber probe measurements were mimicked on agarose-gel phantoms. Even in direct contact, blood layers of 20-40 µm between probe and tissue must be expected, obscuring 405-nm-excited PpIX fluorescence almost completely, but reducing the 633-nm-excited signal only by 25.5%. Thus, 633 nm seems to be the wavelength of choice for PpIX-assisted detection of high-grade gliomas in stereotactic biopsy. PpIX signal attenuation through clinically relevant blood layers for 405 nm (violet) and 633 nm (red) excitation.

Place, publisher, year, edition, pages
Wiley-VCH Verlagsgesellschaft, 2016
Keywords
5-aminolevulinic acid, protoporphyrin IX, stereotactic biopsy, fluorescence spectroscopy, glioblastoma multiforme
National Category
Atom and Molecular Physics and Optics
Identifiers
urn:nbn:se:liu:diva-122640 (URN)10.1002/jbio.201500195 (DOI)000383691800004 ()26564058 (PubMedID)
Note

Funding agencies: German Ministry of Education and Research (BMBF) [01DJ14012B]

Available from: 2015-11-13 Created: 2015-11-13 Last updated: 2017-12-01Bibliographically approved
Markwardt, N., Götz, M., Haj Hosseini, N., Hollnburger, B., Sroka, R., Stepp, H., . . . Rühm, A. (2016). Detection limits of 405 nm and 633 nm excited PpIX fluorescence for brain tumor detection during stereotactic biopsy. In: Jürgen Popp, Valery V. Tuchin, Dennis L. Matthews, Francesco S. Pavone (Ed.), Biophotonics: Photonic Solutions for Better Health Care V: Proceedings of SPIE. Paper presented at Biophotonics: Photonic Solutions for Better Health Care V, Brussels, Belgium, April 4-7, 2016. Brussels: SPIE - International Society for Optical Engineering, 9887, Article ID 98872Z.
Open this publication in new window or tab >>Detection limits of 405 nm and 633 nm excited PpIX fluorescence for brain tumor detection during stereotactic biopsy
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2016 (English)In: Biophotonics: Photonic Solutions for Better Health Care V: Proceedings of SPIE / [ed] Jürgen Popp, Valery V. Tuchin, Dennis L. Matthews, Francesco S. Pavone, Brussels: SPIE - International Society for Optical Engineering, 2016, Vol. 9887, article id 98872ZConference paper, Poster (with or without abstract) (Refereed)
Abstract [en]

5-aminolevulinic-acid-(5-ALA)-induced protoporphyrin IX (PpIX) fluorescence may be used to improve stereotactic brain tumor biopsies. In this study, the sensitivity of PpIX-based tumor detection has been investigated for two potential excitation wavelengths (405 nm, 633 nm). Using a 200 μm fiber in contact with semi-infinite optical phantoms containing ink and Lipovenös, PpIX detection limits of 4.0 nM and 200 nM (relating to 1 mW excitation power) were determined for 405 nm and 633 nm excitation, respectively. Hence, typical PpIX concentrations in glioblastomas of a few μM should be well detectable with both wavelengths. Additionally, blood layers of selected thicknesses were placed between fiber and phantom. Red excitation was shown to be considerably less affected by blood interference: A 50 μm blood layer, for instance, blocked the 405- nm-excited fluorescence completely, but reduced the 633-nm-excited signal by less than 50%. Ray tracing simulations demonstrated that - without blood layer - the sensitivity advantage of 405 nm rises for decreasing fluorescent volume from 50-fold to a maximum of 100-fold. However, at a tumor volume of 1 mm3, which is a typical biopsy sample size, the 633-nm-excited fluorescence signal is only reduced by about 10%. Further simulations revealed that with increasing fiber-tumor distance, the signal drops faster for 405 nm. This reduces the risk of detecting tumor tissue outside the needle's coverage, but diminishes the overlap between optically and mechanically sampled volumes. While 405 nm generally offers a higher sensitivity, 633 nm is more sensitive to distant tumors and considerably superior in case of blood-covered tumor tissue.

Place, publisher, year, edition, pages
Brussels: SPIE - International Society for Optical Engineering, 2016
Series
SPIE - International Society for Optical Engineering. Proceedings, ISSN 0277-786X, E-ISSN 1996-756X ; 9887
Keywords
5-aminolevulinic acid, Fluorescence spectroscopy, Glioblastoma multiforme, Optical phantoms, Protoporphyrin IX, Ray tracing simulations, Stereotactic biopsy
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-130962 (URN)10.1117/12.2225234 (DOI)000387429400044 ()9781510601321 (ISBN)
Conference
Biophotonics: Photonic Solutions for Better Health Care V, Brussels, Belgium, April 4-7, 2016
Note

Funding agencies|German Ministry of Education and Research (BMBF)

Available from: 2016-09-01 Created: 2016-09-01 Last updated: 2018-02-12Bibliographically approved
Haj-Hosseini, N., Milos, P., Hildesjö, C., Hallbeck, M., Richter, J. & Wårdell, K. (2016). Fluorescence spectroscopy and optical coherence tomography for brain tumor detection. In: : . Paper presented at SPIE Photonics Europe, Biophotonics: Photonic Solutions for Better Health Care, Brussels, Belgium, 3 - 7 April 2016 (pp. 9887-96). SPIE - International Society for Optical Engineering
Open this publication in new window or tab >>Fluorescence spectroscopy and optical coherence tomography for brain tumor detection
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2016 (English)Conference paper, Oral presentation with published abstract (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.

Place, publisher, year, edition, pages
SPIE - International Society for Optical Engineering, 2016
Keywords
Brain tumor, fluorescence, optical coherence tomography, hjärntumör, fluorescens, optisk koherenstomografi
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-124008 (URN)
Conference
SPIE Photonics Europe, Biophotonics: Photonic Solutions for Better Health Care, Brussels, Belgium, 3 - 7 April 2016
Funder
Medical Research Council of Southeast Sweden (FORSS)
Available from: 2016-01-18 Created: 2016-01-18 Last updated: 2017-02-02Bibliographically approved
Haj-Hosseini, N., Petersson, P., Gimm, O. & Shabo, I. (2016). Optical Coherence Tomography for Pathological Analysis of Thyroid. In: : . Paper presented at SPIE Photonics West, 16 - 18-February 2016 San Francisco, California, United States. San Francisco
Open this publication in new window or tab >>Optical Coherence Tomography for Pathological Analysis of Thyroid
2016 (English)Conference paper, Poster (with or without abstract) (Refereed)
Place, publisher, year, edition, pages
San Francisco: , 2016
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-126690 (URN)
Conference
SPIE Photonics West, 16 - 18-February 2016 San Francisco, California, United States
Funder
Medical Research Council of Southeast Sweden (FORSS)Linköpings universitet
Available from: 2016-04-01 Created: 2016-04-01 Last updated: 2018-04-25
Haj-Hosseini, N., Milos, P., Richter, J., Hildesjö, C., Hallbeck, M. & Wårdell, K. (2015). Detection of brain tumor using fluorescence and optical coherence tomography. In: : . Paper presented at Medicinteknikdagarna 2015, 13–14 oktober 2015 Uppsala Konsert & Kongress. Uppsala
Open this publication in new window or tab >>Detection of brain tumor using fluorescence and optical coherence tomography
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2015 (English)Conference paper, Oral presentation with published abstract (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.

Place, publisher, year, edition, pages
Uppsala: , 2015
Keywords
fluorescence, optical coherence tomography, brain tumor
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-122286 (URN)
Conference
Medicinteknikdagarna 2015, 13–14 oktober 2015 Uppsala Konsert & Kongress
Funder
Swedish Research CouncilSwedish Childhood Cancer Foundation
Available from: 2015-10-27 Created: 2015-10-27 Last updated: 2017-02-13Bibliographically approved
Haj-Hosseini, N., Richter, J., Hallbeck, M. & Wårdell, K. (2015). Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery. Photodiagnosis and Photodynamic Therapy, 12(2), 209-214
Open this publication in new window or tab >>Low dose 5-aminolevulinic acid: Implications in spectroscopic measurements during brain tumor surgery
2015 (English)In: Photodiagnosis and Photodynamic Therapy, ISSN 1572-1000, E-ISSN 1873-1597, Vol. 12, no 2, p. 209-214Article in journal (Refereed) Published
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.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Fluorescence guided surgery, spectroscopy, quantitative, skin photosensitivity, protoporphyrin IX
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-116711 (URN)10.1016/j.pdpdt.2015.03.004 (DOI)000356554200007 ()
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research VINNOVA
Available from: 2015-04-01 Created: 2015-04-01 Last updated: 2017-12-04Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-0555-8877

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