Assessment of Cerebrovascular Reactivity inPatients with Brain Metastases

Abstract

Introduction: Radiation is an effective treatment to increase overall mean survival of patients with metastatic brain tumours, however, damage to healthy tissue is inevitable. Radiation can cause dysfunction of the cerebrovasculature which is hypothesised to induce cognitive decline in patients after radiotherapy (RT). A new method, the cerebrovascular stress test, is able to visualise cerebrovascular reactivity (CVR) which is the ability of the vessels to dilate after a vasoactive stimulus. Research suggests a link between reduced CVR and cognitive impairment in patients, however, current studies have not yet shown if CVR is reduced in patients with metastatic brain tumours. This thesis aims to assess CVR in patients with metastatic brain tumour at baseline and after RT.
Methods: In this thesis, 13 patients with metastatic brain metastases were included and underwent a magnetic resonance imaging (MRI) scan with a vasoactive stimulus at baseline and three months after the same MRI-scan with stimulus. On the same day as the baseline MRI-scan, the patients received RT. CVR maps were calculated using the MRI-scan with the vasoactive stimulus. An additional computed tomography scan was obtained from each patient prior to their first MRI scan. All scanning data was brought into spatial correspondence with a developed image registration pipeline. After the scanning data was registered image analysis was performed using a VOI- and dose-based analysis.
Results: The performance of the image registration pipeline was close to optimal for the MRI scans, and 69% for the baseline CT scan. The image analysis found a significant increase of CVR at an increasing distance from the tumour for white matter (WM) (p = 0.050). For grey matter (GM) and WM, a significant increase of CVR was found at 14 pixels away from the tumour in comparison to 2 pixels away from the tumour (WM: p = 0.039, and GM: p = 0.046). In the dose-based analysis, a nonsignificant decrease of mean CVR was found after RT. The decrease in CVR after RT did also not depend on the received dose.
Conclusions: This thesis developed an image registration pipeline that can be used in further analysis with this specific patient group and scanning data. The image analysis showed an significant increase in CVR at a distance from the tumour for GM and WM. These results indicate that BM influences the CVR of these patients. However, no conclusions can be drawn based on the dose-based analysis. Additional research needs to be done to relate changes in CVR to cognitive decline in patients with metastatic brain tumours.