Acute Gravitational Stress Selectively Impairs Dynamic Cerebrovascular Reactivity in the Anterior Circulation Independent of Changes to the Central Respiratory Chemoreflex

Cerebrovascular reactivity (CVR) to changes in the partial pressure of arterial carbon dioxide (PaCO2) is an important mechanism that maintains CO2 or pH homeostasis in the brain. To what extent this is influenced by gravitational stress and corresponding implications for the regulation of cerebral blood flow (CBF) remain unclear. The present study examined the onset responses of pulmonary ventilation (V̇E) and anterior middle (MCA) and posterior (PCA) cerebral artery mean blood velocity (Vmean) responses to acute hypercapnia (5% CO2) to infer dynamic changes in the central respiratory chemoreflex and cerebrovascular reactivity (CVR), in supine and 50° head-up tilt (HUT) positions. Each onset response was evaluated using a single-exponential regression model consisting of the response time latency [CO2-response delay (t0)] and time constant (τ). Onset response of V̇E and PCA Vmean to changes in CO2 was unchanged during 50° HUT compared with supine (τ: V̇E, p = 0.707; PCA Vmean, p = 0.071 vs. supine) but the MCA Vmean onset response was faster during supine than during 50° HUT (τ: p = 0.003 vs. supine). These data indicate that gravitational stress selectively impaired dynamic CVR in the anterior cerebral circulation, whereas the posterior circulation was preserved, independent of any changes to the central respiratory chemoreflex. Collectively, our findings highlight the regional heterogeneity underlying CBF regulation that may have translational implications for the microgravity (and hypercapnia) associated with deep-space flight notwithstanding terrestrial orthostatic diseases that have been linked to accelerated cognitive decline and neurodegeneration.

Severity Evaluation of Regional Cerebrovascular Reactivity in Acute Stroke Patients using SPECT

Background: Cerebrovascular reactivity (CVR), as measured using perfusion single photon emission computed tomography (SPECT), is an important indicator for the treatment and prognosis of cerebrovascular disease, but there are few studies of acute stroke or small vascular disease using SPECT. Objective: This study was to evaluate the regional severity with quantitatively determined CVR in patients with acute stroke. Method: Fifty-eight patients who took brain SPECT images were selected to localize quantitative CVR values. The severity of the disease (Grade 1 to 4) was determined through image-based clinical assessment in the absence and presence of a CVR map and their results were compared. Results: In 1st diagnosis without the map, the mean CVR values of Grades 2 and 3 were -6.07% and -9.12%, respectively (P=0.034), while they were -4.78% and -12.34% in 2nd diagnosis with the map, respectively (P<0.001), suggesting that the CVR difference with the map was much more pronounced than without the map. Furthermore, in the ROC analysis, the diagnostic sensitivity between Grades 2 and 3 in 2nd diagnosis (AUC=0.899, P<0.001) was substantially greater than 1st diagnosis (AUC=0.646, P=0.048). Conclusion: This study demonstrated the quantitative CVR maps could reinforce the clinical evaluation of cerebral severity by showing that they can provide statistically significant results between severity and CVR. Furthermore, this study was the first to evaluate the effectiveness of quantitative CVR by examining the difference in the presence or absence of CVR in patients with acute stroke.

Flow augmentation STA-MCA bypass evaluation for patients with acute stroke and unilateral large vessel occlusion: a proposal for an urgent bypass flowchart

OBJECTIVE Endovascular recanalization trials have shown a positive impact on the preservation of ischemic penumbra in patients with acute large vessel occlusion (LVO). The concept of penumbra salvation can be extended to surgical revascularization with bypass in highly selected patients. For selecting these patients, the authors propose a flowchart based on multimodal MRI. METHODS All patients with acute stroke and persisting internal carotid artery (ICA) or M1 occlusion after intravenous lysis or mechanical thrombectomy undergo advanced neuroimaging in a time window of 72 hours after stroke onset including perfusion MRI, blood oxygenation level–dependent functional MRI to evaluate cerebrovascular reactivity (BOLD-CVR), and noninvasive optimal vessel analysis (NOVA) quantitative MRA to assess collateral circulation. RESULTS Symptomatic patients exhibiting persistent hemodynamic impairment and insufficient collateral circulation could benefit from bypass surgery. According to the flowchart, a bypass is considered for patients 1) with low or moderate neurological impairment (National Institutes of Health Stroke Scale score 1–15, modified Rankin Scale score ≤ 3), 2) without large or malignant stroke, 3) without intracranial hemorrhage, 4) with MR perfusion/diffusion mismatch > 120%, 5) with paradoxical BOLD-CVR in the occluded vascular territory, and 6) with insufficient collateral circulation. CONCLUSIONS The proposed flowchart is based on the patient’s clinical condition and multimodal MR neuroimaging and aims to select patients with acute stroke due to LVO and persistent inadequate collateral flow, who could benefit from urgent bypass.

Longitudinal assessment of hemodynamic alterations after mild traumatic brain injury in adolescents: Selected case study review

Alterations in the neurovasculature after traumatic brain injury (TBI) represents a significant sequelae. However, despite theoretical and empirical evidence supporting the near-ubiquity of vascular injury, its pathophysiology remains elusive. Although this has been shown for all grades of TBI, the vascular changes after injuries with the broad mild traumatic brain injuries (mTBI) classification, remain particularly difficult to describe. Our group has previously demonstrated hemodynamic alterations in mTBI by utilizing transcranial Doppler ultrasound and cerebrovascular reactivity in a cross-sectional study. That work identified a phasic progression of deviations over varying days post-injury. These phases were then characterized by a set of inverse models that provided a hypothetical process of hemodynamic dysfunction after mTBI. This model set provides a framework with the potential for guiding clinical treatment over the course of recovery. However, it is still unclear if individual patients will progress through the phases of dysfunction similar to that found at the population level. The work presented here explores six individual patients with high-density data collected during their post-injury recovery. Breath-hold index (BHI) was found to be the most robust feature related to mTBI longitudinally. All six subjects exhibited BHI recovery curves that followed the population model's progression. The changes in pulsatile features lacked the universality of BHI, but were present in subjects with higher self-reported symptom scores and longer periods of recovery. This work suggests neurovascular dysfunction after an mTBI may be a robust phenomenon. Additionally, the capabilities of TCD in capturing these changes highlights its potential for aiding clinicians in monitoring patient's recovery post mTBI.

Hemodynamic and metabolic changes during hypercapnia with normoxia and hyperoxia using pCASL and TRUST MRI in healthy adults

Blood oxygenation level-dependent (BOLD) or arterial spin labeling (ASL) MRI with hypercapnic stimuli allow for measuring cerebrovascular reactivity (CVR). Hypercapnic stimuli are also employed in calibrated BOLD functional MRI for quantifying neuronally-evoked changes in cerebral oxygen metabolism (CMRO2). It is often assumed that hypercapnic stimuli (with or without hyperoxia) are iso-metabolic; increasing arterial CO2 or O2 does not affect CMRO2. We evaluated the null hypothesis that two common hypercapnic stimuli, ‘CO2 in air’ and carbogen, are iso-metabolic. TRUST and ASL MRI were used to measure the cerebral venous oxygenation and cerebral blood flow (CBF), from which the oxygen extraction fraction (OEF) and CMRO2 were calculated for room-air, ‘CO2 in air’ and carbogen. As expected, CBF significantly increased (9.9% ± 9.3% and 12.1% ± 8.8% for ‘CO2 in air’ and carbogen, respectively). CMRO2 decreased for ‘CO2 in air’ (−13.4% ± 13.0%, p < 0.01) compared to room-air, while the CMRO2 during carbogen did not significantly change. Our findings indicate that ‘CO2 in air’ is not iso-metabolic, while carbogen appears to elicit a mixed effect; the CMRO2 reduction during hypercapnia is mitigated when including hyperoxia. These findings can be important for interpreting measurements using hypercapnic or hypercapnic-hyperoxic (carbogen) stimuli.