Neuroimaging Assessment of Cerebrovascular Reactivity in Concussion: Current Concepts, Methodological Considerations, and Review of the Literature

Abstract

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.

Reproducibility of a ramping protocol to measure cerebral vascular reactivity using functional magnetic resonance imaging

“…The use of blood oxygen level dependent (BOLD) MRI to measure CVR is now common in studying conditions such as cerebral stenotic pathologies (Conklin et al, 2010) and traumatic brain injury (Ellis et al, 2016). These assessments are even more attainable with advancing technologies, such as sequential gas delivery (SGD) devices that accurately control P a CO 2 by altering end-tidal CO 2 partial pressure (P et CO 2 ) (Sobczyk et al, 2014) while maintaining arterial oxygen partial pressure (P a O 2 ) (Fisher, Iscoe, & Duffin, 2016;Somogyi et al, 2005).…”

Neurovascular Coupling: A Unifying Theory for Post-Concussion Syndrome Treatment and Functional Neuroimaging

“…Considering PCS, which by definition lacks gross structural injury, the observed BOLD abnormalities are more likely a result of dysfunctional NVC rather than dysfunctional neural activation and likely the predominant source of its symptoms. Further recent studies confirm a central role of NVC disruption in PCS [16][17][18][19][20][21][22].…”

“…Commonly used neuroimaging techniques to measure the effects of these vasoactive stimuli include positron-emission tomography (PET), single photon emission computerized tomography (SPECT), XeCT, transcranial Doppler ultrasonography and non-invasive MRI sequencing such as BOLD and ASL. Considering assessment of CVR in research, these neuroimaging techniques have proven to be highly reliable and reproducible whereas the stimuli used in vasoactivation have not shown the same consistency [18]. This may be due to both the fact that applying the same magnitude and duration of stimulus across all study patients can be inherently difficult and other factors, such as the difference in vasodilatory reserve of the vascular bed in question and the flow reserve of the feeding vessels.…”

“…Effects of CD include decreased anterior and posterior cerebral circulation and decreased global cerebral blood flow (CBF) [27][28][29][30]. The sum of disruption in CVR or a vessel's ability to respond to vasoactive signaling, also plays a role in the reduction of CBF [18,22]. Though largely unelucidated, CVR is disrupted in PCS and is most likely due to the morphologic damage of the cerebral vessels.…”

“…CVR may be defined as the change in CBF in response to a measured vasoactive stimulus [18]. Physiologically, a true independent vasoactive stimulus is the partial pressure of CO 2 in arterial blood (PaCO 2 ).…”