192 Chapter 7 is warranted regarding the potential vascular damage caused by the high fractional doses delivered during SRS, as previous studies have indicated that single fraction doses in particular may contribute to this effect.17 Importantly, the analyses highlighted substantial variations both among patients and within dose regions. Case analyses suggested that part of this heterogeneity could be attributed to tumor progression following SRS. In our case-study we examined three distinct cases with varying responses to SRS, including tumor growth, tumor shrinkage and a mixed response. In the case of new brain metastases growth, there was a deterioration in both physiological MRI parameters and cognitive function, particularly in areas near the tumor which also showed edema increases. Conversely, for the patient with tumor shrinkage, there was an improvement in physiological MRI parameters, specifically in OEF, which corresponded to positive changes in cognitive performance. In the case of a mixed response, less clear patterns emerged from the MRI and cognitive data with both improvements and declines. These results underscore the complex interplay between physiological changes, tumor response, and cognitive outcomes, highlighting the need for individualized assessment and further research in this domain. In this research we used state-of-the-art physiological imaging techniques in a heterogeneous patient population with the goal of identifying potential challenges and opportunities for future research. Due to the sensitivity of physiological MRI measures to acquisition artifacts, stringent patient selection was implemented, yet variations in the data could still arise from measurement and calculation discrepancies. For example, the choice of ASL technique can impact perfusion maps and subsequent CMRO2 calculations. An example is that too short post-labeling delays can lead to arterial transit artefacts or less accurate CBF measures.62–64 We used a multi post-labeling delay ASL pcASL sequence and found CBF values that are close to the ground truth as measured using PET. The QQ-CCTV method used in this study has been validated against the reference standard 15O-PET with a good scan-rescan reproducibility40 and demonstrated sensitivity to detect physiological OEF change, like expected decreased OEF in hypercapnia compared to normoxia65. Also, QQ-CCTV has demonstrated OEF abnormalities in neurologic disorders, including multiple sclerosis66, ischemic stroke67,68, brain tumor69, dementia70, and pre-eclampsia71, and hydrocephalus72. Several limitations should be considered when interpreting the findings of this study. In creating QSM images, the precise positioning of the patients’ head in the main magnetic field (B0) is crucial for accurate dipole inversion, which becomes
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