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Milos, P., Haj-Hosseini, N., Hillman, J. & Wårdell, K. (2023). 5-ALA fluorescence in randomly selected pediatric brain tumors assessed by spectroscopy and surgical microscope. Acta Neurochirurgica, 165(1), 71-81
Open this publication in new window or tab >>5-ALA fluorescence in randomly selected pediatric brain tumors assessed by spectroscopy and surgical microscope
2023 (English)In: Acta Neurochirurgica, ISSN 0001-6268, E-ISSN 0942-0940, Vol. 165, no 1, p. 71-81Article in journal (Refereed) Published
Abstract [en]

Purpose Fluorescence-guided surgery applying 5-aminolevulinic acid (5-ALA) in high-grade gliomas is an established method in adults. In children, results have so far been ambiguous. The aim of this study was to investigate 5-ALA-induced fluorescence in pediatric brain tumors by using the surgical microscope and a spectroscopic hand-held probe. Methods Fourteen randomly selected children (age 4-17) with newly MRI-verified brain tumors were included. No selection was based on the suspected diagnosis prior to surgery. All patients received 5-ALA (20 mg /kg) either orally or via a gastric tube prior to surgery. Intratumoral fluorescence was detected with the microscope and the probe. Moreover, fluorescence in the skin of the forearm was measured. Histopathology samples revealed seven low-grade gliomas, four medulloblastomas, one diffuse intrinsic pontine glioma, one glioblastoma and one atypical meningioma. Blood samples were analyzed, and potential clinical side effects were monitored. Results Microscopically, vague fluorescence was visible in two patients. Intratumoral fluorescence could be detected in five patients with the probe, including the two patients with vague microscopic fluorescence. Three of the oldest children had PpIX fluorescence in the skin. Nine children did not show any fluorescence in the tumor or in the skin. No clinical side effects or laboratory adverse events were observed. Conclusion Fluorescence could not be used to guide surgery in this study, neither with the surgical microscope nor with the hand-held probe. In nine children, no fluorescence was discerned and children with noticeable fluorescence were all older than nine years. 5-ALA was considered safe to apply in children.

Place, publisher, year, edition, pages
Springer, 2023
Keywords
5-ALA, fluorescence, brain tumor, children, spectroscopy
National Category
Medical Instrumentation Surgery Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-187920 (URN)10.1007/s00701-022-05360-1 (DOI)000869218600002 ()36242636 (PubMedID)2-s2.0-85139858033 (Scopus ID)
Funder
Swedish Childhood Cancer Foundation, MT 2013-0043 and MT2016-0013Region Östergötland, LIO-599651Linköpings universitet, LiU Cancer
Note

Funding: Linkoping University; Swedish Childhood Cancer Foundation [MT 2013-0043, MT2016-0013]; LiU Cancer Project Grant; ALF Grant Region Ostergotland, Sweden [LIO-599651]

Available from: 2022-08-31 Created: 2022-08-31 Last updated: 2025-02-10
Bartek, J., Nittby-Redebrandt, H., Sjöberg, R., Milos, P., Hesselager, G. & Jakola, A. (2023). Neurokirurgin alltjämt kärnan i behandlingen av hjärntumörer: [Neurosurgery still pivotal in the diagnostics and treatment of brain tumor patients]. Läkartidningen, 120
Open this publication in new window or tab >>Neurokirurgin alltjämt kärnan i behandlingen av hjärntumörer: [Neurosurgery still pivotal in the diagnostics and treatment of brain tumor patients]
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2023 (Swedish)In: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 120Article, review/survey (Refereed) Published
Abstract [en]

Treatment of adult patients with brain tumors is a multi-disciplinary effort involving several medical disciplines: neurosurgery, oncology, neurology, neuropathology, neuroradiology, and rehabilitation medicine. While the brain tumor field has gone through vast diagnostical changes during the last decade, the hopes of similar achievements in the systemic treatment of these patients with new methods have so far not been fulfilled. As such, neurosurgery still has a pivotal role in the diagnostics and treatment of brain tumor patients. Improved preoperative evaluation of the tumor and adjacent anatomical and functional brain areas, together with advanced microsurgical techniques, intraoperative mapping and monitoring, as well as new minimally invasive techniques, makes brain tumor surgery safer. Indeed, it is now possible to safely operate patients previously considered to have too unfavorable risk-benefit ratio. This article aims at presenting an overview of current neurosurgical treatments of brain tumors.

Abstract [sv]

Behandling av hjärntumörer görs i samverkan mellan flera medicinska discipliner: neurokirurgi, onkologi, neurologi, neuropatologi, neuroradiologi och rehabiliteringsmedicin.

Symtom som talar för förhöjt intrakraniellt tryck, såsom kraftig huvudvärk, illamående, kräkningar och papillödem, bör leda till snabb utredning och kontakt med neurokirurg. 

Förbättrad preoperativ kartläggning av tumören samt angränsande anatomiska och funktionella hjärnområden tillsammans med avancerad mikrokirurgisk teknik, intraoperativ monitorering och visualisering samt nya minimalinvasiva tekniker gör operationer säkrare, och det är i dag möjligt att utföra ingrepp som tidigare ansågs omöjliga eller alltför riskabla.

Place, publisher, year, edition, pages
Läkartidningen Förlag AB, 2023
Keywords
Brain; Brain Neoplasms; Humans; Neurology; Neurosurgery; Neurosurgical Procedures; brain; brain tumor; human; neurology; neurosurgery; procedures
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:liu:diva-200769 (URN)36714931 (PubMedID)2-s2.0-85147064017 (Scopus ID)
Available from: 2024-02-07 Created: 2024-02-07 Last updated: 2024-04-18
Wårdell, K., Klint, E., Milos, P. & Richter, J. (2023). One-Insertion Stereotactic Brain Biopsy Using In Vivo Optical Guidance-A Case Study. Operative Neurosurgery, 25(2), 176-182
Open this publication in new window or tab >>One-Insertion Stereotactic Brain Biopsy Using In Vivo Optical Guidance-A Case Study
2023 (English)In: Operative Neurosurgery, ISSN 2332-4252, E-ISSN 2332-4260, Vol. 25, no 2, p. 176-182Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Stereotactic neurosurgical brain biopsies are afflicted with risks of inconclusive results and hemorrhage. Such complications can necessitate repeated trajectories and prolong surgical time.

OBJECTIVE: To develop and introduce a 1-insertion stereotactic biopsy kit with direct intraoperative optical feedback and to evaluate its applicability in 3 clinical cases.

METHODS: An in-house forward-looking probe with optical fibers was designed to fit the outer cannula of a side-cutting biopsy kit. A small aperture was made at the tip of the outer cannula and the edges aligned with the optical probe inside. Stereotactic biopsies were performed using the Leksell Stereotactic System. Optical signals were measured in millimeter steps along the preplanned trajectory during the insertion. At the region with the highest 5-aminolevulinic acid (5-ALA)-induced fluorescence, the probe was replaced by the inner cannula, and tissue samples were taken. The waiting time for pathology diagnosis was noted.

RESULTS: Measurements took 5 to 10 minutes, and the surgeon received direct visual feedback of intraoperative 5-ALA fluorescence, microcirculation, and tissue gray-whiteness. The 5-ALA fluorescence corroborated with the pathological findings which had waiting times of 45, 50, and 75 minutes. Because only 1 trajectory was required and the patient could be prepared for the end of surgery immediately after sampling, this shortened the total surgical time.

CONCLUSION: A 1-insertion stereotactic biopsy procedure with real-time optical guidance has been presented and successfully evaluated in 3 clinical cases. The method can be modified for frameless navigation and thus has great potential to improve safety and diagnostic yield for both frameless and frame-based neurosurgical biopsy procedures.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2023
Keywords
5-aminolevulinic acid (5-ALA); Biopsy; Fluorescence; Hemorrhage; Laser Doppler flowmetry (LDF); Microcirculation; Spectroscopy
National Category
Neurology Surgery
Identifiers
urn:nbn:se:liu:diva-194955 (URN)10.1227/ons.0000000000000722 (DOI)001031296900039 ()37083519 (PubMedID)2-s2.0-85160233691 (Scopus ID)
Note

Funding: Swedish Foundation for Strategic Research [RMX-18-0056]

Available from: 2023-06-13 Created: 2023-06-13 Last updated: 2025-02-21Bibliographically approved
Richter, J., Haj-Hosseini, N., Milos, P., Hallbeck, M. & Wårdell, K. (2021). Optical Brain Biopsy with a Fluorescence and Vessel Tracing Probe. Operative Neurosurgery, 21(4), 217-224
Open this publication in new window or tab >>Optical Brain Biopsy with a Fluorescence and Vessel Tracing Probe
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2021 (English)In: Operative Neurosurgery, ISSN 2332-4252, E-ISSN 2332-4260, Vol. 21, no 4, p. 217-224Article in journal (Refereed) Published
Abstract [en]

BACKGROUND Accurate stereotactic biopsies of brain tumors are imperative for diagnosis and tailoring of the therapy. Repetitive needle insertions enhance risks of brain lesioning, hemorrhage, and complications due to prolonged procedure.

OBJECTIVE To investigate clinical benefits of a combined 5-aminolaevulinic acid (5-ALA) fluorescence and laser Doppler flowmetry system for the detection of malignant brain tumor and blood vessels in stereotactic biopsies.

METHODS Planning of targets and trajectories was followed by optical measurements in 20 patients, using the Leksell Stereotactic System and a manual insertion device. Fluorescence spectra, microvascular blood flow, and tissue grayness were recorded each millimeter along the paths. Biopsies were taken at preplanned positions. The diagnoses were compared with the fluorescence signals. The recordings were plotted against measurement positions and compared. Sites indicating a risk of hemorrhage were counted as well as the time for the procedures.

RESULTS Signals were recorded along 28 trajectories, and 78 biopsies were collected. The final diagnosis showed 17 glioblastomas, 2 lymphomas, and 1 astrocytoma grade III. Fluorescence was seen along 23 of the paths with 4 having the peak of 5-ALA fluorescence 3 mm or more from the precalculated target. There was increased microcirculation in 40 of 905 measured positions. The measurement time for each trajectory was 5 to 10 min.

CONCLUSION The probe provided direct feedback of increased blood flow along the trajectory and of malignant tissue in the vicinity of the target. The method can increase the precision and the safety of the biopsy procedure and reduce time.

Place, publisher, year, edition, pages
Oxford University Press, 2021
Keywords
Biopsy, Optical, Tumor, Fluorescence, Spectroscopy, Stereotactic navigation, 5-ALA
National Category
Other Medical Engineering Surgery
Identifiers
urn:nbn:se:liu:diva-179467 (URN)10.1093/ons/opab216 (DOI)000702156000006 ()34192763 (PubMedID)
Funder
Linköpings universitet, LiU Cancer Strategic Research GrantSwedish Childhood Cancer Foundation, MT 2013-0043Region Östergötland, ALF: LIO-599651Swedish Foundation for Strategic Research , RMX18-0056
Note

Funding: LiU Cancer Strategic Research Grant; Swedish Childhood Cancer FoundationEuropean Commission [MT 20130043]; ALF Grants Region Ostergotland; Swedish Foundation for Strategic ResearchSwedish Foundation for Strategic Research [RMX18-0056]

Available from: 2021-09-21 Created: 2021-09-21 Last updated: 2023-03-28Bibliographically approved
Carstam, L., Smits, A., Milos, P., Corell, A., Henriksson, R., Bartek, J. J. & Jakola, A. S. (2019). Neurosurgical patterns of care for diffuse low-grade gliomas in Sweden between 2005 and 2015. Neuro-Oncology Practice, 6(2), 124-133
Open this publication in new window or tab >>Neurosurgical patterns of care for diffuse low-grade gliomas in Sweden between 2005 and 2015
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2019 (English)In: Neuro-Oncology Practice, ISSN 2054-2577, E-ISSN 2054-2585, Vol. 6, no 2, p. 124-133Article in journal (Refereed) Published
Abstract [en]

Background. In the last decade, increasing evidence has evolved for early and maximal safe resection of diffuse low-grade gliomas (LGGs) regarding survival. However, changes in clinical practice are known to occur slowly and we do not know if the scientific evidence has yet resulted in changes in neurosurgical patterns of care. Methods. The Swedish Brain Tumor Registry was used to identify all patients with a first-time histopathological diagnosis of LGG between 2005 and 2015. For analysis of surgical treatment patterns, we subdivided assessed time periods into 2005-2008, 2009-2012, and 2013-2015. Population-based data on patient and disease characteristics, surgical management, and outcomes were extracted. Results. A total of 548 patients with diffuse World Health Organization grade II gliomas were identified: 142 diagnosed during 2005-2008, 244 during 2009-2012, and 162 during 2013-2015. Resection as opposed to biopsy was performed in 64.3% during 2005-2008, 74.2% during 2009-2012, and 74.1% during 2013-2015 (P =.08). There was no difference among the 3 periods regarding overall survival (P =.11). However, post hoc analysis of data from the 4 (out of 6) centers that covered all 3 time periods demonstrated a resection rate of 64.3% during 2005-2008, 77.4% during 2009-2012, and 75.4% during 2013-2015 (P =.02) and longer survival of patients diagnosed 2009 and onward (P =.04). Conclusion. In this nationwide, population-based study we observed a shift over time in favor of LGG resection. Further, a positive correlation between the more active surgical strategy and longer survival is shown, although no causality can be claimed because of possible confounding factors.

Place, publisher, year, edition, pages
Oxford University Press, 2019
Keywords
diffuse low-grade glioma; glioma/surgery; neurosurgery; patterns of care; treatment outcome
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-164460 (URN)10.1093/nop/npy023 (DOI)000462820700006 ()30949360 (PubMedID)2-s2.0-85064265657 (Scopus ID)
Note

Funding Agencies|Goteborg Medical Society (Goteborgs Lakaresallskap); Agreement Concerning Research and Education of Doctors (Avtal om lakarutbildning och forskning) [ALFGBG-695611]; Swedish Research Council (Vetenskapsradet)Swedish Research Council [2017-00944]

Available from: 2020-03-28 Created: 2020-03-28 Last updated: 2020-12-03Bibliographically approved
Haj-Hosseini, N., Richter, J., Milos, P., Hallbeck, M. & Wårdell, K. (2019). Optical guidance during stereotactic brain tumor biopsy. In: : . Paper presented at Medicinteknikdagarna 2019, 2-3 Okt., Linköping. Linköping
Open this publication in new window or tab >>Optical guidance during stereotactic brain tumor biopsy
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2019 (English)Conference paper, Oral presentation only (Other academic)
Place, publisher, year, edition, pages
Linköping: , 2019
Keywords
Biopsy procedures, biooptics, brain tumor, fluorescence, laser Doppler
National Category
Medical Engineering
Identifiers
urn:nbn:se:liu:diva-175394 (URN)
Conference
Medicinteknikdagarna 2019, 2-3 Okt., Linköping
Available from: 2021-09-20 Created: 2021-09-20 Last updated: 2021-11-10Bibliographically approved
Wårdell, K., Milos, P., Haj-Hosseini, N., Richter, J., Hallbeck, M. & Hillman, J. (2019). Optical measurements with 5-ALA during surgical resection of brain tumors in children. In: : . Paper presented at MTdagarna, Linköping, Oct. 2-3 2019.
Open this publication in new window or tab >>Optical measurements with 5-ALA during surgical resection of brain tumors in children
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2019 (English)Conference paper, Oral presentation only (Other academic)
National Category
Surgery
Identifiers
urn:nbn:se:liu:diva-174607 (URN)
Conference
MTdagarna, Linköping, Oct. 2-3 2019
Available from: 2021-03-25 Created: 2021-03-25 Last updated: 2021-03-30Bibliographically approved
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: 2023-02-17Bibliographically 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: 2019-10-14Bibliographically approved
Haj-Hosseini, N., Richter, J., Milos, P., Hallbeck, M. & Wårdell, K. (2017). Optical Guidance for Brain Tumor Stereotactic Biopsy. In: : . Paper presented at European Medical and Biological Engineering Conference (EMBEC) and the Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC). Tampere
Open this publication in new window or tab >>Optical Guidance for Brain Tumor Stereotactic Biopsy
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2017 (English)Conference paper, Oral presentation with published abstract (Refereed)
Place, publisher, year, edition, pages
Tampere: , 2017
National Category
Other Medical Engineering
Identifiers
urn:nbn:se:liu:diva-137473 (URN)
Conference
European Medical and Biological Engineering Conference (EMBEC) and the Nordic-Baltic Conference on Biomedical Engineering and Medical Physics (NBC)
Funder
Östergötland County CouncilSwedish Childhood Cancer Foundation
Available from: 2017-05-16 Created: 2017-05-16 Last updated: 2021-07-27Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0002-8951-0263

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