222 Chapter 9 autoregulation system ensures adequate supply of oxygen and nutrients to the brain.79,80 CVR is a crucial component of cerebral autoregulation, since it facilitates regulation of CBF by either dilation or constriction of arterial control vessels.81–83 In cases where blood flow compensation is inadequate to meet the metabolic demands of brain tissue (e.g. when dilatory reserve is pathologically exhausted), higher oxygen extraction from the blood, as measured through the oxygen extraction fraction (OEF), serves as an additional regulatory mechanism to maintain oxygen delivery to the tissue. This delicate balance between CBF and OEF supports a consistent cerebral metabolic rate of oxygen (CMRO2) consumption. 84 Thus, while CVR can provide information on the vascular reserve capacity, OEF can help gain insight into the metabolic reserve capacity of the brain. As illustrated above, the brain’s reserve capacity is dependent on a balance of both metabolic and vascular factors. This underscores that focusing on solely one of these factors will provide an incomplete picture as each factor provides a separate piece of the puzzle. This was corroborated by the research presented in Chapter 6. Thus, the pathophysiology underlying radiation-induced cognitive decline most likely also reflects this multifactorial nature. So far, cerebral hemodynamics have only rarely been investigated in patients with brain tumors. Most of this work has focused on using the hemodynamic status of the BMs to predict their response after radiotherapy.85 In the case of gliomas, impaired CVR has been observed both within the glioma tissue itself 86 and in the whole brain. 86 Therefore, it has been speculated that whole-brain CVR could potentially serve as an indicator of antitumor treatment efficacy. However, the relationship between hemodynamic changes and cognitive functioning after cranial radiotherapy, remains to be elucidated. In Chapter 7 I therefore investigated different physiological measures using MRI both before and three months after SRS. In this preliminary analysis, a wide variety of post-radiotherapy changes was observed in both healthy-appearing brain tissue and edematous tissue surrounding the BMs, highlighting the sensitivity of these physiological MRI measures. Moreover, some of these changes seemed related to the received radiotherapy dose and post-radiotherapy cognitive changes, requiring further exploration in larger patient samples. However, in order to comprehensively evaluate the effects of SRS, it is imperative to take into account the temporal aspect of these effects. Given that SRS has been associated with a range of long-term side-effects than can persist for months to several years, the three-months’ time window used in the APRICOT study may not have been sufficient to capture the entirety of post-radiotherapy changes. Therefore, it would be advised to extend the observation period beyond three months to encompass potential long-term effects as well.
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