Continuous Time-Domain Cerebrovascular Reactivity Metrics and Discriminate Capacity for the Upper and Lower Limits of Autoregulation: A Scoping Review of the Animal Literature

Abstract

Over a wide range of systemic arterial pressures, cerebral blood flow (CBF) is regulated fairly constantly by the cerebral vessels in a process termed cerebral autoregulation (CA), which is depicted by the Lassen autoregulatory curve. After traumatic brain injury (TBI), CA can get impaired and these impairments manifest in changes of the Lassen autoregulatory curve. Continuous surrogate metrics of pressure-based CA, termed cerebrovascular reactivity (CVR) metrics, evaluate the relationship between slow vasogenic fluctuations in a driving pressure for cerebral blood flow, and the most commonly studied and utilized measures are based in the time domain and have been increasingly applied in bedside TBI care and have sparked the investigation of individualized cerebral perfusion pressure targets. However, not all CVR metrics have been validated as true measures of autoregulation in the pre-clinical setting. We reviewed all available pre-clinical animal literature that assessed the association between continuous time-domain metrics of CVR and some aspect of the Lassen autoregulatory curve. All 15 articles found associated the evaluated continuous metrics to the lower limit of autoregulation curve whereas none looked at the upper limit. Most of the evaluated metrics showed the ability to discriminate the lower limit of autoregulation with various methods of perturbation. Further work is required to evaluate the utility of such surrogate measures against the upper limit of autoregulation, while also providing validation to the existing literature supporting specific indices and their ability to discriminate the lower limit.

Optimal bispectral index level of sedation and cerebral oximetry in traumatic brain injury: a non-invasive individualized approach in critical care?

“…While COx_a utility remains in its infancy, there is a growing literature body that evaluates the similarity between NIRS-based cerebrovascular reactivity measures and the more standard PRx [25][26][27][28][29][30]. This is evidenced by pre-clinical literature providing only validation for ICP and NIRS-based cerebrovascular reactivity indices as true measures of the lower limit of autoregulation in several different animal models [31]. This strong association between NIRS and cerebral blood flow/cerebral blood volume is also supported by the growing objective body of literature supporting a moderate/strong correlation between NIRS measures and cerebral blood flow [49,50].…”

“…Recent work has established that the cerebral oximetry index (COx_a), which assesses the slow wave vasogenic changes between near-infrared spectroscopy (NIRS) based regional brain tissue oxygenation (rSO 2 ) and ABP, is comparable to PRx [25][26][27][28][29][30]. Similarly, the COx_a indices have been shown in pre-clinical literature to measure aspects of the Lassen autoregulatory curve [31][32][33][34][35][36]. This non-invasive measure of cerebrovascular reactivity determination opens the potential to evaluate cerebral autoregulation in non-TBI cohorts, and explore personalized cerebral physiologic targets focused on neuroprotection in such populations.…”

High spatial and temporal resolution cerebrovascular reactivity for humans and large mammals: A technological description of integrated fNIRS and niABP mapping system

“…The CVR metrics are defined as moving Pearson’s correlation coefficients between slow-wave (i.e., 0.05–0.005 Hz) ( Howells et al, 2015 ) fluctuations in a driving pressure for CBF, such as CPP/MAP, and a surrogate for pulsatile CBV/CBF, such as oxyhemoglobin (HbO), deoxyhemoglobin (HHb) or rSO 2 ( Lee et al, 2009 ; Brady et al, 2010 ; Zweifel et al, 2010b ; Zeiler et al, 2017a ; 2017b ; Mathieu et al, 2020 ; Gomez et al, 2021a ; Gomez and Zeiler, 2021 ; Zeiler, 2021 ). These NIRS-based indices have been validated in animal models to accurately detect the LLA ( Brady et al, 2008 ; 2010 ; Lee et al, 2009 ; Sainbhi et al, 2021 ) and clinical data support associations with ICP based cerebrovascular reactivity measurement through rough estimates ( Zweifel et al, 2008 ; 2010a ; Zeiler et al, 2017a ; 2017b ). However, further work is required to understand the importance of NIRS-based cerebrovascular indices.…”

“…Preclinical models are scarce to validate these measures against the Lassen autoregulatory curve. A recent systematically conducted scoping review from our group has demonstrated that most measured indices, namely ICP and NIRS based metrics, were able to accurately distinguish CPP/MAP from above and below the LLA in pre-clinical models ( Sainbhi et al, 2021 ). However, none of the studies were able to assess the ULA due to cardiac failure at higher CPP/MAP in these animal models ( Sainbhi et al, 2021 ).…”

Cerebral Autoregulation Monitoring in Traumatic Brain Injury: An Overview of Recent Advances in Personalized Medicine

“…Similarly, literature assessing the association between continuous CA metrics and NIRSbased rSO 2 delivery is underdeveloped. 79,[89][90][91][92][93][94] In general, studies assessing the utility of NIRS in moderate/severe TBI are limited, as highlighted in a recent systematic review on the topic. 79 NIRS-based CA metrics do closely co-vary with standard ICP-derived versions.…”