Multimodal monitoring has been gaining traction in the critical care of patients following traumatic brain injury (TBI). Through providing a deeper understanding of the individual patient’s comprehensive physiologic state, or “physiome,” following injury, these methods hold the promise of improving personalized care and advancing precision medicine. One of the modalities being explored in TBI care is near-infrared spectroscopy (NIRS), given it’s non-invasive nature and ability to interrogate microvascular and tissue oxygen metabolism. In this narrative review, we begin by discussing the principles of NIRS technology, including spatially, frequency, and time-resolved variants. Subsequently, the applications of NIRS in various phases of clinical care following TBI are explored. These applications include the pre-hospital, intraoperative, neurocritical care, and outpatient/rehabilitation setting. The utility of NIRS to predict functional outcomes and evaluate dysfunctional cerebrovascular reactivity is also discussed. Finally, future applications and potential advancements in NIRS-based physiologic monitoring of TBI patients are presented, with a description of the potential integration with other omics biomarkers.

The process of cerebral vessels regulating constant cerebral blood flow over a wide range of systemic arterial pressures is termed cerebral autoregulation (CA). Static and dynamic autoregulation are two types of CA measurement techniques, with the main difference between these measures relating to the time scale used. Static autoregulation looks at the long-term change in blood pressures, while dynamic autoregulation looks at the immediate change. Techniques that provide regularly updating measures are referred to as continuous, whereas intermittent techniques take a single at point in time. However, a technique being continuous or intermittent is not implied by if the technique measures autoregulation statically or dynamically. This narrative review outlines technical aspects of non-invasive and minimally-invasive modalities along with providing details on the non-invasive and minimally-invasive measurement techniques used for CA assessment. These non-invasive techniques include neuroimaging methods, transcranial Doppler, and near-infrared spectroscopy while the minimally-invasive techniques include positron emission tomography along with magnetic resonance imaging and radiography methods. Further, the advantages and limitations are discussed along with how these methods are used to assess CA. At the end, the clinical considerations regarding these various techniques are highlighted.

Cerebral blood flow (CBF) is an important physiologic parameter that is vital for proper cerebral function and recovery. Current widely accepted methods of measuring CBF are cumbersome, invasive, or have poor spatial or temporal resolution. Near infrared spectroscopy (NIRS) based measures of cerebrovascular physiology may provide a means of non-invasively, topographically, and continuously measuring CBF. We performed a systematically conducted scoping review of the available literature examining the quantitative relationship between NIRS-based cerebrovascular metrics and CBF. We found that continuous-wave NIRS (CW-NIRS) was the most examined modality with dynamic contrast enhanced NIRS (DCE-NIRS) being the next most common. Fewer studies assessed diffuse correlation spectroscopy (DCS) and frequency resolved NIRS (FR-NIRS). We did not find studies examining the relationship between time-resolved NIRS (TR-NIRS) based metrics and CBF. Studies were most frequently conducted in humans and animal studies mostly utilized large animal models. The identified studies almost exclusively used a Pearson correlation analysis. Much of the literature supported a positive linear relationship between changes in CW-NIRS based metrics, particularly regional cerebral oxygen saturation (rSO₂), and changes in CBF. Linear relationships were also identified between other NIRS based modalities and CBF, however, further validation is needed.

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.

Since its creation in the 1980s, transcranial Doppler (TCD) has provided a method of non-invasively monitoring cerebral physiology and has become an invaluable tool in neurocritical care. In this narrative review, we examine the role TCD has in the management of the moderate and severe traumatic brain injury (TBI) patient. We examine the principles of TCD and the ways in which it has been applied to gain insight into cerebral physiology following TBI, as well as explore the clinical evidence supporting these applications. Its usefulness as a tool to non-invasively determine intracranial pressure, detect post-traumatic vasospasm, predict patient outcome, and assess the state of cerebral autoregulation are all explored.

There has been little change in morbidity and mortality in traumatic brain injury (TBI) in the last 25 years. However, literature has emerged linking impaired cerebrovascular reactivity (a surrogate of cerebral autoregulation) with poor outcomes post-injury. Thus, cerebrovascular reactivity (derived through the pressure reactivity index; PRx) is emerging as an important continuous measure. Furthermore, recent literature indicates that autonomic dysfunction may drive impaired cerebrovascular reactivity in moderate/severe TBI. Thus, to improve our understanding of this association, we assessed the physiological relationship between PRx and the autonomic variables of heart rate variability (HRV), blood pressure variability (BPV), and baroreflex sensitivity (BRS) using time-series statistical methodologies. These methodologies include vector autoregressive integrative moving average (VARIMA) impulse response function analysis, Granger causality, and hierarchical clustering. Granger causality testing displayed inconclusive results, where PRx and the autonomic variables had varying bidirectional relationships. Evaluating the temporal profile of the impulse response function plots demonstrated that the autonomic variables of BRS, ratio of low/high frequency of HRV and very low frequency HRV all had a strong relation to PRx, indicating that the sympathetic autonomic response may be more closely linked to cerebrovascular reactivity, then other variables. Finally, BRS was consistently associated with PRx, possibly demonstrating a deeper relationship to PRx than other autonomic measures. Taken together, cerebrovascular reactivity and autonomic response are interlinked, with a bidirectional impact between cerebrovascular reactivity and circulatory autonomics. However, this work is exploratory and preliminary, with further study required to extract and confirm any underlying relationships.