223 Discussion In Chapter 6, our study highlighted the distinction between CBF acquired during Arterial Spin Labeling (ASL) MRI and BOLD-CVR, indicating that they do not convey identical information. Consequently, relying solely on ASL may not be sufficient to comprehensively evaluate subtle post-radiotherapy vascular changes. However, the clinical implementation of BOLD-CVR, particularly with the use of a sequential gas delivery system like that used in the APRICOTstudy, may encounter limitations due to its restricted availability in hospitals. To enhance clinical applicability, it would be valuable to investigate whether breath holds or resting state CVR can offer similar insights into CVR. Both are less invasive and more feasible techniques in clinical settings, but may not be able to convey the dynamic and rapid changes in CVR. Although some studies in healthy controls have shown the robustness and repeatability of breath holds in healthy volunteers87–89, a comprehensive study in BMs patients is yet to be conducted. Expanding the investigation to include this patient group would further enrich our understanding of the potential utility of BHs as a surrogate marker for assessing post-radiotherapy changes. BOLD-CVR measurements, like those used in Chapter 6 and 7, have been widely used to assess the ability of blood vessels to dilate in response to a hemodynamic stimulus.90 It is important to acknowledge that this technique provides an indirect measure of the CVR response. That is, active dilation predominantly occurs in arteries, while veins passively dilate in response to increased blood volume. However, the BOLD response primarily reflects changes in blood oxygenation in veins. In contrast, Vascular-Space-Occupancy (VASO) fMRI can detect changes in arterial cerebral blood volume (aCBV), making it a possible valuable alternative for directly assessing CVR.91 A recent study illustrated the potential value of VASO fMRI in assessing autoregulatory aCBV and CBF compensation strategies in patients with steno-occlusive disease.92 However, VASO fMRI has lower signal-to-noise ratio compared to BOLD fMRI and limited availability due to specific imaging requirements constraining its widespread adoption and clinical application.91 Another area of interest for future research on vascular and metabolic changes is the capillary transit time, or more specifically capillary transit-time heterogeneity (CTH). In healthy individuals, cerebral perfusion demonstrates a homogenous distribution of capillary transit times. A high CTH indicates a combination of capillaries with low blood flows and long transit times, as well as capillaries with high flows and short transit times. Not only does the low perfusion in some capillaries negatively affect the oxygen delivery to the tissue, but the short transit times in other capillaries also allow less time for oxygen to diffuse into the surrounding tissue, thereby reducing the oxygen extraction fraction.93,94 Thereby, a high CTH could decrease the oxygen 9
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