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On potentials and limitations of perfusion MRI in neurological disorders
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Radiology.
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Description
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 [en]
Neurological disease, MRI, Perfusion, 15O-water PET
National Category
Radiology, Nuclear Medicine and Medical Imaging
Research subject
Medical Radiophysics
Identifiers
URN: urn:nbn:se:uu:diva-404604ISBN: 978-91-513-0883-8 (print)OAI: oai:DiVA.org:uu-404604DiVA, id: diva2:1410798
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
List of papers
1. Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response
Open this publication in new window or tab >>Perfusion Magnetic Resonance Imaging Changes in Normal Appearing Brain Tissue after Radiotherapy in Glioblastoma Patients may Confound Longitudinal Evaluation of Treatment Response
2018 (English)In: Radiology and Oncology, ISSN 1318-2099, E-ISSN 1581-3207, Vol. 52, no 2, p. 143-151Article in journal (Refereed) Published
Abstract [en]

Background: The aim of this study was assess acute and early delayed radiation-induced changes in normal-appearing brain tissue perfusion as measured with perfusion magnetic resonance imaging (MRI) and the dependence of these changes on the fractionated radiotherapy (FRT) dose level.

Patients and methods: Seventeen patients with glioma WHO grade III-IV treated with FRT were included in this prospective study, seven were excluded because of inconsistent FRT protocol or missing examinations. Dynamic susceptibility contrast MRI and contrast-enhanced 3D-T1-weighted (3D-T1w) images were acquired prior to and in average (standard deviation): 3.1 (3.3), 34.4 (9.5) and 103.3 (12.9) days after FRT. Pre-FRT 3D-T1w images were segmented into white- and grey matter. Cerebral blood volume (CBV) and cerebral blood flow (CBF) maps were calculated and co-registered patient-wise to pre-FRT 3D-T1w images. Seven radiation dose regions were created for each tissue type: 0-5 Gy, 5-10 Gy, 10-20 Gy, 20-30 Gy, 30-40 Gy, 40-50 Gy and 50-60 Gy. Mean CBV and CBF were calculated in each dose region and normalised (nCBV and nCBF) to the mean CBV and CBF in 0-5 Gy white- and grey matter reference regions, respectively.

Results: Regional and global nCBV and nCBF in white- and grey matter decreased after FRT, followed by a tendency to recover. The response of nCBV and nCBF was dose-dependent in white matter but not in grey matter.

Conclusions: Our data suggest that radiation-induced perfusion changes occur in normal-appearing brain tissue after FRT. This can cause an overestimation of relative tumour perfusion using dynamic susceptibility contrast MRI, and can thus confound tumour treatment evaluation.

Keywords
malignant gliomas, normal-appearing brain tissue, perfusion MRI, radiation-induced changes
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-356784 (URN)10.2478/raon-2018-0022 (DOI)000433103400004 ()30018517 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2020-03-01Bibliographically approved
2. 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
Open this publication in new window or tab >>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
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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.

National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-346813 (URN)10.1177/2058460118808811 (DOI)000450106500001 ()30542625 (PubMedID)
Funder
Swedish Cancer Society
Available from: 2018-03-21 Created: 2018-03-21 Last updated: 2020-03-01Bibliographically approved
3. Evaluation of pseudo-continuous arterial spin labeling MRI – agreement with 15O-water PET with arterial input function and use of integrated PET/MR
Open this publication in new window or tab >>Evaluation of pseudo-continuous arterial spin labeling MRI – agreement with 15O-water PET with arterial input function and use of integrated PET/MR
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(English)Manuscript (preprint) (Other academic)
Keywords
ASL, CBF, PET/MR, validation, 15O-water
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-404602 (URN)
Available from: 2020-02-27 Created: 2020-02-27 Last updated: 2020-03-05
4. High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease
Open this publication in new window or tab >>High Intravascular Signal Arterial Transit Time Artifacts Have Negligible Effects on Cerebral Blood Flow and Cerebrovascular Reserve Capacity Measurement Using Single Postlabel Delay Arterial Spin-Labeling in Patients with Moyamoya Disease
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2020 (English)In: American Journal of Neuroradiology, ISSN 0195-6108, E-ISSN 1936-959XArticle in journal (Refereed) Epub ahead of print
National Category
Radiology, Nuclear Medicine and Medical Imaging
Identifiers
urn:nbn:se:uu:diva-405377 (URN)10.3174/ajnr.A6411 (DOI)
Available from: 2020-02-27 Created: 2020-02-27 Last updated: 2020-03-05

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