163 Hemodynamic Imaging in Brain Metastases: ASL vs. Hypercapnic BOLD technique may influence the resulting perfusion maps. An example is that too short post-labeling delays can lead to arterial transit artefacts or less accurate CBF measures.3,51,52 In the current study, we used a multi post-labeling delay ASL pcASL sequence and did not perform partial volume correction leading to CBF values that are close to the ground truth as measured using PET. A disadvantage of BOLD-metrics, is that the BOLD response is dependent on multiple factors, like changes in cerebral blood volume, cerebral metabolic rate of oxygen consumption, arterial partial pressure of oxygen and baseline parameters like hematocrit, OEF, CMRO2, and blood volume. 53,54 This makes it difficult to pinpoint the exact underlying mechanisms and could be viewed as a less pure measure of brain hemodynamics when compared to ASL. Nevertheless, on average the change in BOLD to changes in PetCO2 seem to be dominated by CBF changes 43,55,56 Thereby it could be speculated that the BOLD response is mainly affected by changes in CBF and provides a good comparison with ASL MRI. Additionally, specific analyses choices could have influenced results. In areas with vascular steal, low variability in CVR values in combination with highly variable hemodynamic lag values were observed. As steal regions were defined by any CVR value below zero, these regions could thereby include voxels containing noisy, just below threshold CVR values, thereby influencing the results. Moreover, as the current analysis pipeline is influenced by the time to peak for the hemodynamic lag calculation, it may be difficult to discern the actual lag time of the response. Thereby hemodynamic lag values will not always reflect true underlying temporal characteristics of tissue reactivity. Therefore, we advise not to perform lag analysis within regions indicated by vascular steal as it will possibly lead to spurious lag quantifications. To further understand the exact hemodynamic mechanisms, oxygen extraction fraction (OEF) would be a valuable additional metric. To illustrate, in regions with exhausted cerebral autoregulation, a further reduction in cerebral perfusion pressure will cause CBF to drop. In order to maintain tissue function, OEF can be increased. The functional consequences of reduced regional CBF will therefore only become apparent when OEF is maximal.4 Thus, future studies should add OEF measurements to further understand whether tissue at risk as indicated by either ASL or CVR is also reflective of tissue with maximized OEF. To fully understand the functional consequences of these hemodynamic measure, the MRI metrics should be related to behavioral measures, like cognitive performance. 6
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