We typically apply an increase in the arterial partial pressure of carbon dioxide (PaCO 2) to induce global dilation in the cerebral vasculature and observe the patterns of changes in cerebral blood flow (CBF). To test for the presence of effective collateral blood flow distal to a steno-occlusive lesion, a vasodilatory challenge must be applied to the system while observing changes in surrogates of blood flow, like the BOLD signal, in the vascular territory of the compromised supply vessel(s). One can, however, follow changes in tissue perfusion through its effect on tissue oxygenation as reflected by the capillary deoxyhemoglobin concentration and its effect on the MRI blood oxygen-level dependent (BOLD) signal. Furthermore, the collateral flow passing through tissue arterioles, and capillaries ( Moody et al., 1990) is below the resolution of clinical imaging modalities, visible only as a contrast blush on angiography, and exceptionally difficult to quantify. Collateral vessels may not contribute to perfusion if downstream tissue requirements are met via the native pathways. Such collateral flow may not be reliably detected by angiography ( Ben Hassen et al., 2019). The status of collateral blood flow is of particular interest in the presence of known large artery steno-occlusive lesions, especially if accompanied by transient neurological symptoms. In the case of upstream obstructions, there is the potential for trophic forces to stimulate the development of new vessels especially in the setting of slowly progressive occlusions as in moyamoya ( Scott and Smith, 2009).

Under such conditions, adequate perfusion can be restored only when blood flow bypasses the impediment via an alternate route, referred to as collateral blood supply ( Moody et al., 1990 Sobczyk et al., 2020 reviewed in Sheth and Liebeskind, 2015 Figure 1).

However, the mechanisms can be compromised under a variety of conditions that harm vessels or reroute blood flow, including steno-occlusive processes, emboli, thrombosis, vascular malformations, tumors, and vasculitis. The vascular mechanisms affecting these functions are highly coordinated and very effective in health. Cerebrovascular physiology has evolved to maintain this supply in the face of reduced perfusion pressure through autoregulation or, when needed, to provide a surge in supply through neurovascular coupling ( Willie et al., 2014). This includes providing oxygen and nutrients as well as eliminating metabolic waste. In this essay, we review what we believe were our most valuable – and sometimes controversial insights during our two decades-long journey.īrain vascular health relates to a fundamental ability of the cerebrovascular system to match blood flow to tissue demand. The trajectory of our understanding did not follow a logical linear progression rather, it emerged as a coalescence of new, old, and previously dismissed, ideas that had accumulated over time. Over the past 20 years, our work has delivered nuanced insights into normal cerebral vascular physiology, as well as adaptive physiological responses in the presence of disease. We developed a standard stimulus and attempted to measure, classify, and interpret the many forms of responses.

Ideally, the stimulus is standardized across patients, and in a single patient over time. A stimulus-response approach is effective in interrogating the physiology of its vasculature.

5Techna Institute & Koerner Scientist in MR Imaging, University Health Network, Toronto, ON, Canada.

4The Joint Department of Medical Imaging, Toronto Western Hospital, University of Toronto, Toronto, ON, Canada.

3Joint Department of Medical Imaging and the Functional Neuroimaging Lab, University Health Network, Toronto, ON, Canada.

2Department of Anaesthesia and Pain Management, University Health Network, University of Toronto, Toronto, ON, Canada.

1Department of Physiology, University of Toronto, Toronto, ON, Canada.

Cerebrovascular reactivity definition