Michael J. Ellis, Lawrence Ryner, Olivia Sobczyk, Jorn Fierstra, David J. Mikulis, Joseph A. Fisher, James Duffin, W. Alan C. Mutch
5 min
Concussion is frequently characterized by subjective symptoms and normal findings on standard clinical neuroimaging. Emerging research suggests that the underlying pathophysiology involves a mismatch between cerebral blood flow (CBF) and the metabolic demands of the brain. Cerebrovascular reactivity (CVR) provides a way to test the integrity of this regulatory system by measuring how blood flow changes in response to a controlled vasoactive stimulus. By applying a stimulus—typically a gas mixture that induces vasodilation—researchers can observe whether the brain's vascular beds respond symmetrically or if specific regions show impaired capacity, which may indicate underlying injury.
In healthy brains, the neurovascular unit ensures that blood flow increases to meet metabolic needs. In traumatic brain injury (TBI), this coupling is often disrupted, leading to secondary injury processes like ischemia and edema. While studies in moderate and severe TBI have long used CVR to predict outcomes, its application in concussion is relatively new. Preliminary research indicates that even when clinical symptoms resolve, patients may continue to exhibit regional abnormalities in resting CBF. CVR testing offers a potential method to unmask these persistent vascular dysregulations that remain invisible to conventional structural imaging.
To be clinically useful, CVR assessment requires high-resolution imaging and a standardized, reproducible stimulus. Common MRI techniques like Blood Oxygen Level-Dependent (BOLD) imaging and Arterial Spin Labeling (ASL) are frequently used as surrogates for CBF. However, these methods have distinct limitations. BOLD signal changes are proportional to CBF only under specific conditions, and the relationship can become unreliable if the brain's oxygen consumption is altered by injury. Furthermore, the lack of a universally standardized vasoactive stimulus makes it difficult to compare results across different research studies, highlighting the need for rigorous methodological consistency before CVR can be adopted as a standard diagnostic tool for concussion.
Concussion is a form of traumatic brain injury (TBI) that presents with a wide spectrum of subjective symptoms and few objective clinical findings. Emerging research suggests that one of the processes that may contribute to concussion pathophysiology is dysregulation of cerebral blood flow (CBF) leading to a mismatch between CBF delivery and the metabolic needs of the injured brain. Cerebrovascular reactivity (CVR) is defined as the change in CBF in response to a measured vasoactive stimulus. Several magnetic resonance imaging (MRI) techniques can be used as a surrogate measure of CBF in clinical and laboratory studies. In order to provide an accurate assessment of CVR, these sequences must be combined with a reliable, reproducible vasoactive stimulus that can manipulate CBF. Although CVR imaging currently plays a crucial role in the diagnosis and management of many cerebrovascular diseases, only recently have studies begun to apply this assessment tool in patients with concussion. In order to evaluate the quality, reliability, and relevance of CVR studies in concussion, it is important that clinicians and researchers have a strong foundational understanding of the role of CBF regulation in health, concussion, and more severe forms of TBI, and an awareness of the advantages and limitations of currently available CVR measurement techniques. Accordingly, in this review, we (1) discuss the role of CVR in TBI and concussion, (2) examine methodological considerations for MRI-based measurement of CVR, and (3) provide an overview of published CVR studies in concussion patients.
Sam: So the healthy parts of the brain are essentially pulling blood away from the injured parts, just because the injured parts have lost their ability to compete for it.
Alex: That's the mechanism, and it's called a vascular steal. The total amount of blood reaching the brain might look normal overall, but underneath that, there are local imbalances that can leave injured regions starved. That's why someone can pass a standard cognitive test and still feel foggy, slow, or off-balance for weeks.
Sam: It's not that the damage is invisible—we were just looking with the wrong tool.
Alex: That's a fair way to put it. And the complexity doesn't stop there. Even in healthy people, blood flow naturally varies between different brain regions, so researchers can't just flag anything that looks unusual. They need a reference point.
Sam: How do they figure out what's actually abnormal versus just natural variation?
Alex: They use standardized brain maps—essentially a template built from data on healthy brains. A patient's scan gets aligned to that template, and then each tiny section of the brain, called a voxel—think of it as a three-dimensional pixel—gets a score. If a region's score falls outside the normal range, it gets flagged and color-coded on the map. A doctor can then see, quite literally, where the vascular bottleneck is located.
Sam: That's much more concrete than trying to interpret symptoms. But I'd imagine other conditions could produce similar-looking results on these maps?
Alex: That's a critical limitation the paper acknowledges. Migraines, for instance, also affect blood flow. So a scan that looks like a concussion injury might reflect something pre-existing. This technique is presented as a powerful supplement to clinical assessment—not a standalone diagnostic tool, at least not yet.
Sam: And what about timing? If blood flow can look normal on a standard scan while still being disrupted underneath, how long does that disruption actually last?
Alex: The paper points to studies showing that abnormal blood flow patterns can persist for weeks, even after a patient has passed standard cognitive tests and reported feeling better. That gap is significant. It suggests that the window of true biological recovery may be considerably longer than the window of felt recovery.
Sam: Which has real consequences. If someone returns to contact sports before that biological recovery is complete, they're taking on risk that no symptom checklist would catch.
Alex: Precisely. That's where the practical value of this approach lies. Rather than asking "how do you feel?"—which depends entirely on a patient's self-awareness and honesty—you'd have an objective measure of whether the brain's regulatory system has actually returned to normal.
Sam: So the longer-term goal is to make this kind of scan a routine part of the return-to-play process.
Alex: That's the direction the research is pointing. The work ahead involves refining these markers, establishing clearer thresholds for what counts as recovered, and making the process practical enough for clinical settings. But the underlying insight—that the brain's vascular response is a more sensitive indicator of concussion recovery than structure alone—is what this paper is building the case for. Thanks for listening to ResearchPod.