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Dynamic Contrast-Enhanced Magnetic Resonance Imaging May Act as a Biomarker for Vascular Damage in Normal Appearing Brain Tissue after Radiotherapy in Patients with Glioblastoma
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Experimental and Clinical Oncology.
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2018 (English)In: Acta Radiologica Open, ISSN 2058-4601, Vol. 7, no 11Article in journal (Refereed) Published
Abstract [en]

Background: Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a promising perfusion method and may be useful in evaluating radiation-induced changes in normal-appearing brain tissue.

Purpose: To assess whether radiotherapy induces changes in vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) derived from DCE-MRI in normal-appearing brain tissue and possible relationships to radiation dose given.

Material and Methods: Seventeen patients with glioblastoma treated with radiotherapy and chemotherapy were included; five were excluded because of inconsistencies in the radiotherapy protocol or early drop-out. DCE-MRI, contrast-enhanced three-dimensional (3D) T1-weighted (T1W) images and T2-weighted fluid attenuated inversion recovery (T2-FLAIR) images were acquired before and on average 3.3, 30.6, 101.6, and 185.7 days after radiotherapy. Pre-radiotherapy CE T1W and T2-FLAIR images were segmented into white and gray matter, excluding all non-healthy tissue. Ktrans and Ve were calculated using the extended Kety model with the Parker population-based arterial input function. Six radiation dose regions were created for each tissue type, based on each patient's computed tomography-based dose plan. Mean Ktrans and Ve were calculated over each dose region and tissue type.

Results: Global Ktrans and Ve demonstrated mostly non-significant changes with mean values higher for post-radiotherapy examinations in both gray and white matter compared to pre-radiotherapy. No relationship to radiation dose was found.

Conclusion: Additional studies are needed to validate if Ktrans and Ve derived from DCE-MRI may act as potential biomarkers for acute and early-delayed radiation-induced vascular damages. No dose-response relationship was found.

Place, publisher, year, edition, pages
2018. Vol. 7, no 11
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
URN: urn:nbn:se:uu:diva-346813DOI: 10.1177/2058460118808811ISI: 000450106500001PubMedID: 30542625OAI: oai:DiVA.org:uu-346813DiVA, id: diva2:1192184
Funder
Swedish Cancer SocietyAvailable from: 2018-03-21 Created: 2018-03-21 Last updated: 2020-03-01Bibliographically approved
In thesis
1. Perfusion MRI of the brain after radiotherapy in patients with glioblastoma – potential and problems
Open this publication in new window or tab >>Perfusion MRI of the brain after radiotherapy in patients with glioblastoma – potential and problems
2018 (English)Licentiate thesis, comprehensive summary (Other academic)
Abstract [en]

Perfusion Magnetic Resonance Imaging (MRI) is a useful tool in diagnostic evaluation and treatment response assessment in patients with glioblastoma. The standard treatment regimen includes surgical resection, radiotherapy and adjuvant chemotherapy. However, prognosis is poor; relative 5-year survival is 3–5%. Radiotherapy sequelae may have considerable negative effects on the patients’ quality of life. Acute and early delayed radiation-induced injury is primarily considered damage to the cerebral vascular tissue.

 

The general aim of this study was to evaluate how perfusion MRI evaluation, based on contrast agent administration (DSC- and DCE-MRI), is affected by or can be useful to assess radiation-induced changes in normal appearing brain tissue in patients with glioblastoma after radiotherapy.

 

Paper I: Dynamic Susceptibility Contrast (DSC)-MRI is a common perfusion MRI method in clinical practice in patients with glioblastoma. Due to inherent limitations, cerebral blood volume (CBV) and cerebral blood flow (CBF) derived from DSC-MRI are normalized to contralateral normal appearing white matter. Ten patients with glioblastoma were examined. Regional and global normalized CBV and normalized CBF in white and gray matter decreased after radiotherapy, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in gray matter. In conclusion, radiotherapy effects on normal appearing white matter can confound treatment evaluation with DSC-MRI in patients with glioblastoma.

 

Paper II: Dynamic Contrast Enhanced (DCE)-MRI may be useful in evaluating radiation-induced damage in normal appearing brain tissue.  DCE-MRI-derived parameters, vascular permeability (Ktrans) and the fractional volume of the extravascular extracellular space (Ve) are potential biomarkers. Twelve patients with glioblastoma were examined. A tendency toward increased Ktrans and Ve was seen, suggesting that these parameters may act as potential biomarkers for acute and early delayed radiation-induced vascular damage

Place, publisher, year, edition, pages
Uppsala: Uppsala universitet, 2018
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-346814 (URN)
Presentation
2018-04-13, Akademiska Sjukhuset, Uppsala, 12:00 (Swedish)
Supervisors
Available from: 2018-04-04 Created: 2018-04-03 Last updated: 2018-04-04Bibliographically approved
2. On potentials and limitations of perfusion MRI in neurological disorders
Open this publication in new window or tab >>On potentials and limitations of perfusion MRI in neurological disorders
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cerebral perfusion outlines several parameters which describe the status of cerebral haemodynamics. Numerous neurological diseases affect cerebral perfusion, thus the importance of diagnostic measurements. Perfusion magnetic resonance imaging (MRI) is a collection of non-ionizing magnetic resonance-based perfusion measurement techniques that can be used for clinical assessment of cerebral perfusion. The aim of this thesis was to investigate potentials and limitations of perfusion MRI used for clinical assessment of patients with neurological disorders. Patients with glioblastoma were examined with dynamic susceptibility contrast MRI (DSC-MRI) and dynamic contrast enhanced MRI (DCE-MRI) before/after treatment with fractionated radiotherapy (FRT). Radiation-induced changes in normal-appearing brain tissue were found in the form of decreased cerebral blood volume (CBV) and cerebral blood flow (CBF) measured with DSC-MRI and increased vascular permeability and increased fraction of the extravascular extracellular space measured with DCE-MRI. Papers I–II provide valuable information regarding the possibility that radiation-induced changes could be a confounder in DSC-MRI and that DCE-MRI could potentially act as a biomarker for vascular damage secondary to radiation exposure. Additionally, CBF derived from arterial spin labelling (ASL) was compared to the reference standard 15O-water positron emission tomography (PET). Simultaneous measurements were acquired with an integrated PET/MR scanner using arterial blood sampling and zero-echo time-based attenuation correction in healthy subjects and patients with epilepsy. Correlation- and Bland–Altman analysis showed fair correlation and a negative relationship with wide limits of agreement in several cortical and subcortical regions. Thus, agreement with 15O-water is insufficient for absolute quantification with ASL, but ASL provides reliable relative measures that could potentially be rescaled to absolute values. Moyamoya disease (MMD) is characterized by progressive stenosis/occlusion in large brain arteries. A limitation of ASL is the sensitivity to prolonged arterial transit times, which is common in the collateral vessels of the brain in patients with MMD. Given the non-invasiveness and non-ionizing exposure, ASL has a pronounced potential for use in diagnostic imaging in patients with MMD. ASL was performed before and after administration of acetazolamide; CBF and cerebrovascular reserve capacity were derived for large vascular regions. Artefacts originating from prolonged arterial transit times were found to have negligible effects on CBF and cerebrovascular reserve capacity derived from ASL. This thesis adds to the understanding of potential and limitations of perfusion MRI in neurological diseases. 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2020. p. 63
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1642
Keywords
Neurological disease, MRI, Perfusion, 15O-water PET
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medical Radiophysics
Identifiers
urn:nbn:se:uu:diva-404604 (URN)978-91-513-0883-8 (ISBN)
Public defence
2020-04-17, H:Son-Holmdahlsalen, Akademiska Sjukhuset, Ing 100 2 tr, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2020-03-26 Created: 2020-03-01 Last updated: 2020-03-26

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Fahlström, MarkusFransson, SamuelBlomquist, ErikLarsson, Elna-Marie

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