Cerebral Vasoreactivity Research Articles

Cerebrovascular hemodynamics association with brain structure and function in Multiple Sclerosis

BackgroundVascular risk factors seem to contribute to disease progression in Multiple Sclerosis (MS), but the mechanistic connection between vascular risk and MS is unknown. Understanding cerebrovascular hemodynamics (CVH) in MS may help advance our understanding of the link between vascular risk and MS. ObjectivesExamine the relationship between CVH [dynamic cerebral autoregulation (dCA) and vasoreactivity (VR)] and brain structure (MRI) and function (cognition, and gait) in individuals with MS. MethodsTranscranial Doppler ultrasound (TCD) was utilized to assess two key markers of CVH: dCA and VR. dCA (reported as phase and gain) is calculated from the spontaneous blood pressure and flow velocity oscillations. VR is calculated as the slope of change in cerebral blood flow velocity in response to end-tidal CO2. Global gray matter (GM), white matter (WM), WM hyperintensity (WMH) volumes and WM lesion counts were measured from brain MRI. All participants underwent detailed cognitive and gait assessments. ResultsEighty participants were included (age 44 ± 11, 26 % male); 75 had relapsing-remitting MS (94 %), with disease duration of 8 (11) years [median (IQR)] since MS diagnosis and an Expanded Disability Status Scale (EDSS) of 2.0 (4.0). Higher phase (better dCA) was associated with greater GM volume, lower WHM burden and higher cognitive scores in the memory and global cognitive domains (all P values <0.05). There was no relationship between CVH and gait speed in our study participants. There was no relationship between VR and any measures of brain structure and function. ConclusionsMore efficient cerebral autoregulation is associated with better brain structure (larger GM and lower WMH volumes) and function (cognition, but not gait) in patients with MS.

Exploring Resveratrol Intervention in Managing Menopausal Symptoms: A Comprehensive Systematic Review of Clinical Trials

Introduction: Menopause, a significant event in a woman's reproductive lifespan, entails hormonal changes and a range of symptoms affecting various bodily systems. Conventional treatments like hormone replacement therapy (HRT) have limitations and associated risks, prompting interest in alternative therapies such as resveratrol. Materials/Methods: The literature search was conducted in six databases. The outcome of interest measures the mean changes in bone mineral density (BMD), Quality of Life (QoL), bone biomarkers, menopause symptoms, and cognitive and mood functions pre- and post-interventions. Resveratrol was administered in various forms and doses, including trans-resveratrol 75 mg twice or once daily, 250/500/1000 mg resveratrol tablets, and a combination of fermented soy containing 10 mg equol and 25 mg resveratrol. Quality appraisal was done using the Cochrane Risk of Bias Tool 2. Results: Resveratrol supplementation in post-menopausal women, involving 745 participants across various studies, has shown remarkable health benefits. These include improved cerebral vasoreactivity (CVR) to hypercapnia, a 10% decrease in overall pain, and enhanced quality of life. Additionally, resveratrol boosts flow-mediated dilation (FMD) by 23% and increases serum sex hormone-binding globulin (SHBG) concentrations by 10%, benefiting bone mineral density (BMD). Over the long term, it leads to a significant 35% increase in FMD and a substantial 33% enhancement in overall cognitive performance, highlighting its diverse benefits. Conclusion: For women in the post-menopausal stage, resveratrol supplementation shows potential for improving cardiovascular health, relieving pain, enhancing quality of life, supporting bone health, boosting cognitive function, and promoting overall mental well-being.

Impact of Fat Distribution and Metabolic Diseases on Cerebral Microcirculation: A Multimodal Study on Type 2 Diabetic and Obese Patients.

Background: Since metabolic diseases and atherosclerotic vascular events are firmly associated, herein we investigate changes in central microcirculation and atherosclerosis-related body fat distribution in patients with type 2 diabetes mellitus and obesity. Methods: Resting brain perfusion single-photon emission computed tomography (SPECT) imaging with Technetium-99m hexamethylpropylene amine oxime ([99mTc]Tc-HMPAO SPECT) was performed, and the breath-holding index (BHI) and carotid intima-media thickness (cIMT) were measured to characterise central microcirculation. Besides CT-based abdominal fat tissue segmentation, C-peptide level, glycaemic and anthropometric parameters were registered to search for correlations with cerebral blood flow and vasoreactivity. Results: Although no significant difference was found between the resting cerebral perfusion of the two patient cohorts, a greater blood flow increase was experienced in the obese after the breath-holding test than in the diabetics (p < 0.05). A significant positive correlation was encountered between resting and provocation-triggered brain perfusion and C-peptide levels (p < 0.005). BMI and cIMT were negatively correlated (rho = -0.27 and -0.23 for maximum and mean cIMT, respectively), while BMI and BHI showed a positive association (rho = 0.31 and rho = 0.29 for maximum and mean BHI, respectively), which could be explained by BMI-dependent changes in fat tissue distribution. cIMT demonstrated a disproportional relationship with increasing age, and higher cIMT values were observed for the men. Conclusions: Overall, C-peptide levels and circulatory parameters seem to be strong applicants to predict brain microvascular alterations and related cognitive decline in such patient populations.

The clinical and neuroimaging differences between vascular parkinsonism and Parkinson's disease: a case-control study.

Parkinson's disease (PD) and vascular parkinsonism (VaP) have highly overlapping phenotypes, and different prognosis. This study comprehensively investigated the clinical, brain MRI and transcranial sonography differences between VaP and PD. Forty-eight patients with PD, 27 patients with VaP, and 29 healthy controls were compared. All patients were assessed using the MDS-UPDRS, Berg Balance Scale (BBS), Ten-Meter Walking Test (10-MWT), Time Up and Go Test, and Non-Motor Symptoms Scale. Beck Depression Inventory, PD questionnaire- 39, international urine incontinence scale, cognitive assessment scales, MRI brain and transcranial colour-coded doppler. The study was registered on clinical-Trial.gov (NCT04308135) on 03/12/2020. VaP patients showed significantly older age of onset, shorter disease duration, lower drug doses and levodopa responsiveness, higher On and Off axial scores, On and Off BBS, higher On scores for PIGD, rigidity, bradykinesia and total motor MDS-UPDRS, lower On and Off tremor, lower-half predominance, lower asymmetrical presentation and symmetric index than PD patients. VaP patients had worse non-motor symptoms Scale (NMSS) than controls except for perceptual problems/hallucinations but better symptoms than PD patients except for urinary dysfunction. Quality of life (QoL) was impaired in VaP patients and was correlated with motor function and NMSs. The VaP group had significantly higher white matter lesions and brain atrophy, with lower hyperechogenicity of the substantia nigra and more impaired cerebral vascular resistance and vasoreactivity than the PD group. VaP has a characteristic motor and non-motor profile, with impaired QoL, white matter, and transcranial sonography abnormalities that differentiate it from PD. Further studies are warranted to explore the role of vascular lesions in the pathogenesis of VaP. The registered identifier NCT04308135 on clinical-Trial.gov. Registered on 03/12/2020.

Point-of-care brain ultrasound and transcranial doppler or color-coded doppler in critically ill neonates and children.

In critically ill neonates, brain ultrasound for diagnosis and follow-up of the most common cerebral pathologies of the neonatal period may be considered the standard of care. Data are needed about the possible role of doppler techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles. In pediatric critical care, doppler based techniques should be routinely adopted to assess and monitor cerebral hemodynamics. New technologies and more evidence are needed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. • In critically ill neonates, brain ultrasound for early diagnosis and follow-up of the most common cerebral and neurovascular pathologies of the neonatal period is a cornerstone of daily practice. In critically ill children, doppler-based techniques are more routinely used to assess cerebral hemodynamics and autoregulation after acute brain injury and to screen patients at risk for vasospasm or stroke (e.g., sickle cell diseases, right-to-left shunts). • In critically ill neonates, research is currently focusing on the use of novel high frequency probes, even higher than 10 MHz, especially for extremely preterm babies. Furthermore, data are needed about the role of doppler based techniques for the assessment of cerebral perfusion and vasoreactivity of the critically ill neonate with open fontanelles, also integrated with a non-invasive assessment of brain oxygenation. In pediatric critical care, new technologies should be developed to improve the accuracy of brain ultrasound for the assessment of brain parenchyma of critically ill children with fibrous fontanelles. Furthermore, large multicenter studies are needed to clarify role and accuracy of doppler-based techniques to assess cerebral perfusion pressure and its changes after treatment interventions.

Slow‐breathing induced hypocapnia mitigates deficit of vasoreactivity measured in patients with cognitive impairment

AbstractBackgroundA multi‐center study in Los Angeles (USC), Kansas City (KUMC) and Dallas (UT‐SWMC) has been quantifying the dynamics of CO2 vasoreactivity in MCI/AD patients and cognitively normal controls under spontaneous resting conditions. The goal is to develop effective vasoreactivity physio‐markers for early diagnosis of MCI and pre‐clinical AD, based on previous findings of significantly reduced vasoreactivity in MCI patients [Marmarelis et al., J. Alzh. Dis. 56:89‐105, 2017]. Here, we report on the effects of slow‐paced breathing upon these physio‐markers.MethodSpontaneous changes in arterial blood pressure (ABP), end‐tidal CO2 (etCO2), and cerebral blood flow velocity (CBFV) in middle cerebral arteries were recorded under resting conditions over two 6‐8 min sessions, separated by session of slow‐paced breathing (6 breaths/minute), in 47 MCI and 25 AD patients and 58 age‐matched cognitively normal controls. Using our novel methodology, we obtained predictive models of the dynamic effects of ABP and etCO2 upon CBFV using the universal convolutional form of linear dynamic models, which are defined by the respective “kernels” estimated from time‐series data. The etCO2‐to‐CBFV kernel is used to compute indices (physio‐markers) that quantify the vasoreactivity in each participant.ResultThe vasoreactivity index for each participant is computed from the integrated etCO2‐to‐CBFV kernel as the time‐average over the first 30 sec. The average kernels for patients and controls are shown in Figures 1‐2 for the two sessions respectively. Note the smaller kernel values for patients – while the difference is reduced after slow‐paced breathing. The obtained vasoreactivity indices are significantly smaller for 72 patients (MCI and AD taken together) vs 58 controls for the first session [p = 0.018; mean (SD): 0.057 (0.539) vs 0.424 (1.076)] but NOT for the session after slow‐paced breathing [p = 0.237; mean (SD): 0.193 (0.731) vs 0.361 (0.863)]. Average etCO2 was lower after paced‐breathing [p = 10−6; mean (SD): 36.23 (6.18) vs 33.44 (6.36)].ConclusionQuantitative analysis of cerebral CO2 vasoreactivity under resting spontaneous conditions in 72 MCI/AD patients vs 58 age‐matched controls, before and after slow‐paced breathing, revealed that the significant vasoreactivity deficit in MCI/AD patients is mitigated (at least temporarily) after slow‐paced breathing. This effect may be due to observed hypocapnia induced by slow‐paced breathing.

Endothelin Receptor Blockade Improves Cerebral Blood Flow-Mediated Dilation in a Mouse Model of Alzheimer’s Disease

Introduction: Cerebral blood flow (CBF) is reduced in patients with Alzheimer’s disease (AD). Flow-mediated dilation (FMD), which plays a key role in the regulation of blood flow, is attenuated by endothelin-1. We hypothesized that endothelin receptor blockade may improve CBF in AD. Methods: We investigated cerebrovascular reactivity in a mouse model of AD (APP-PS1; 5-6-month-old male subjects). We assessed the in vivo response to normoxic hypercapnia and in vitro FMD in isolated cerebral and mesenteric resistance arteries before and after endothelin receptor blockade (bosentan). Results: Normoxic hypercapnia increased basilar trunk blood flow velocity (+12.3 ± 2.4%; p = 0.006, n = 6) in wild-type (WT) mice but reduced blood flow in APP-PS1 mice (−11.4 ± 1.2%; p < 0.0001, n = 8). Bosentan (50 mg/kg, acute intraperitoneal injection) restored cerebrovascular reactivity in APP-PS1 mice (+10.2 ± 2.2%; p < 0.0001, n = 8) but had no effect in WT. FMD was reduced in the posterior cerebral artery of APP-PS1 compared to WT and was normalized by bosentan (1 μmol/L, 30 min, or 50 mg/kg/day for 28 days). FMD was similar in the mesenteric artery of APPS-PS1 and WT. Conclusion: APP-PS1 mice exhibited cerebrovascular endothelial dysfunction. Acute and chronic blockade of endothelin receptors restored endothelial vasomotor function, suggesting a promising therapeutic approach to restoring cerebral vasoreactivity in AD.

Comparison of Near-Infrared Spectroscopy-Based Cerebral Autoregulatory Indices in Extremely Low Birth Weight Infants.

Premature infants are born with immature cerebral autoregulation function and are vulnerable to pressure passive cerebral circulation and subsequent brain injury. Measurements derived from near-infrared spectroscopy (NIRS) have enabled continuous assessment of cerebral vasoreactivity. Although NIRS has enabled a growing field of research, the lack of clear standardization in the field remains problematic. A major limitation of current literature is the absence of a comparative analysis of the different methodologies. To determine the relationship between NIRS-derived continuous indices of cerebral autoregulation in a cohort of extremely low birth weight (ELBW) infants. Premature infants of birth weight 401-1000 g were studied during the first 72 h of life. The cerebral oximetry index (COx), hemoglobin volume index (HVx), and tissue oxygenation heart rate reactivity index (TOHRx) were simultaneously calculated. The relationship between each of the indices was assessed with Pearson correlation. Fifty-eight infants with a median gestational age of 25.8 weeks and a median birth weight of 738 g were included. Intraventricular hemorrhage (IVH) was detected in 33% of individuals. COx and HVx demonstrated the highest degree of correlation, although the relationship was moderate at best (r = 0.543, p < 0.001). No correlation was found either between COx and TOHRx (r = 0.318, p < 0.015) or between HVx and TOHRx (r = 0.287, p < 0.029). No significant differences in these relationships were found with respect to IVH and no IVH in subgroup analysis. COx, HVx, and TOHRx are not numerically equivalent. Caution must be applied when interpreting or comparing results based on different methodologies for measuring cerebral autoregulation. Uniformity regarding data acquisition and analytical methodology are needed to firmly establish a gold standard for neonatal cerebral autoregulation monitoring.

Cerebral perfusion in type 2 diabetes mellitus: A preliminary study with MR perfusion

BackgroundType 2 diabetes mellitus (T2DM) is associated with altered cerebral vasoreactivity, cognitive impairment, and functional decline. Magnetic Resonance (MR) perfusion can be used to assess cerebral blood flow (CBF). The aim of this study is to analyze the association between diabetes mellitus and cerebral perfusion. MethodsThe study included 52 patients diagnosed with T2DM and 39 healthy individuals. The diabetic patients were classified into three groups (PRP: proliferative retinopathy, NPRP: non-proliferative retinopathy, Non-RP: non-retinopathy DM). The rCBF measurements of cortical gray matter and thalami were carried out using the region of interest. Reference quantitative measurements were performed from ipsilateral white matter. ResultsThe comparison between the T2DM group and the control group revealed that rCBF values of bilateral frontal lobes, cingulate gyrus, medial temporal lobe, thalami and right occipital lobe were measured to be significantly lower in the T2DM group (p < 0.05). No significant difference was detected between the two groups in terms of rCBF values of the left occipital lobe and anterior aspect of the left temporal lobe (p > 0.05). The rCBF values were lower in the anterior aspect of the right temporal lobe and the difference showed borderline statistical significance (p = 0.058). No significant difference was detected regarding mean rCBF values measured in the regions of cerebral hemispheres among the three patient groups with T2DM (p˃0.05). ConclusionRegional hypoperfusion was encountered in most of the lobes in the T2DM group when compared with the healthy group. However, in terms of rCBF values, there was no significant difference among the three groups with T2DM.

HIGH SALT DIET ALTERS CEREBROVASCULAR RESISTANCE IN RESPONSE TO ORTHOSTATIC TEST IN HEALTHY YOUNG INDIVIDUALS

Objective: High salt (HS) diet has been shown to impairs vascular reactivity in animal models, by increasing vasoconstriction to different stimuli. Response to orthostasis occurs via activation of baroreceptor reflex leading to increase in total peripheral resistance that prevents significant fall of arterial blood pressure (ABP) while standing up, aiming to preserve cerebral perfusion pressure. We recently showed that HS diet physiologically suppresses sympathetic arm of autonomic control in healthy humans (Stupin et al. Nutrients 2021; 13:1731. https://doi.org/10.3390/nu13051731). Present study aimed to assess the effect of HS diet on cerebral vasoreactivity in response to orthostatic load. Design and method: Twenty-seven young healthy participants (F:21, M:6, age range 19–24) consumed 7-day low-salt (LS) diet (&lt;2.3 g NaCl /day) and afterwards 7-day HS diet (&gt;11.2 g NaCl/day). In response to orthostatic test cerebral and systemic hemodynamic parameters, arterial blood pressure, heart rate variability and heart rate, and were recorded simultaneously with transcranial Doppler ultrasound and The Task Force® Monitor. Results: Subjects maintained normotension during HS diet. Diastolic blood pressure, as well as mean cerebral blood flow (CBF) and the velocity time integral decreased, while cerebral pulsatility index increased after standing up following both dietary protocols. However, while no change was observed in total peripheral resistance, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Baroreflex sensitivity (BRS), sympathetic neural control, serum plasma renin activity and aldosterone, and urine noradrenaline and vanillylmandelic acid concentration was significantly decreased in HS diet. Conclusions: Results demonstrated that following 7-day HS diet, enhanced cerebral autoregulation preserves CBF and is manifested as increased cerebral vascular resistance, in conditions with blunted BRS and sympathetic activity. The study has been published in Eur J Appl Physiol. 2023 Jan 4. doi: 10.1007/s00421-022-05124-w. Online ahead of print.

Cerebrovascular Phenotype in Fabry Disease Patients Assessed by Ultrasound.

Fabry disease (FD) is a rare X-linked lysosomal storage disorder with variable phenotypes, including neurological symptoms. These can be influenced by vascular impairment. Extracranial and transcranial vascular sonography is an effective and noninvasive method for measuring arterial structures and blood flow. The study aims to investigate cerebrovascular phenotype characteristics in FD patients compared to controls using neurosonology. This is a single-center, cross-sectional study of 130 subjects-65 patients (38 females), with genetically confirmed FD, and 65 sex- and age-matched controls. Using ultrasonography, we measured structural and hemodynamic parameters, including distal common carotid artery intima-media thickness, inner vertebral artery diameter, resting blood flow velocity, pulsatility index, and cerebral vasoreactivity (CVR) in the middle cerebral artery. To assess differences between FD and controls and to identify factors influencing investigated outcomes, unadjusted and adjusted regression analyses were performed. In comparison to sex- and age-matched controls, FD patients displayed significantly increased carotid artery intima-media thickness (observed FD 0.69 ± 0.13 mm versus controls 0.63 ± 0.12 mm; Padj = .0014), vertebral artery diameter (observed FD 3.59 ± 0.35 mm versus controls 3.38 ± 0.33 mm; Padj = .0002), middle cerebral artery pulsatility index (observed FD 0.98 ± 0.19 versus controls 0.87 ± 0.11; Padj < .0001), and significantly decreased CVR (observed FD 1.21 ± 0.49 versus controls 1.35 ± 0.38; Padj = .0409), when adjusted by age, BMI, and sex. Additionally, FD patients had significantly more variable CVR (0.48 ± 0.25 versus 0.21 ± 0.14; Padj < .0001). Our results suggest the presence of multiple vascular abnormalities and changes in hemodynamic parameters of cerebral arteries in patients with FD.

Altered Cerebral Vasoreactivity on Transcranial Color-Coded Sonography Related to Akinetic-Rigid Phenotype of Parkinson's Disease: Interim Analysis of a Cross-Sectional Study.

A correlation between worse functional outcomes in Parkinson's disease (PD) patients with cerebrovascular disease (CVD) or the Akinetic-rigid phenotype has been argued in recent studies. We aimed to evaluate the association of cerebral hemodynamics impairments, assessed by Transcranial Color-coded Doppler sonography (TCCS), on PD patients with different phenotypes of the disease and with risk factors for CVD. Idiopathic PD patients (n = 51) were divided into motor subtypes: Akinetic-rigid (AR) (n = 27) and Tremor-dominant (TD) (n = 24) and into two groups regarding vascular risk factors: when ≥2 were present (PDvasc) (n = 18) and <2 (PDnvasc) (n = 33). In a parallel analysis, the Fazekas scale on brain magnetic resonance imaging (MRI) was applied to a sample to assess the degree of leukoaraiosis. TCCS examinations were prospectively performed obtaining middle cerebral artery Mean Flow Velocities (Vm), Resistance Index (RI), and Pulsatility Index (PI). The Breath-Holding Index (BHI) was calculated to assess cerebrovascular reactivity (cVR). Standardized functional scales were administered (UPDRS III and Hoehn&Yahr). The phenotype groups were similar in age, disease duration and demographic parameters, but there were significantly higher H&Y scores than TD group. cVR was impaired in 66.7% of AR vs. 37.5% of TD. AR group exhibited lower BHI (0.53 ± 0.31 vs. 0.91 ± 0.62; p = 0.000), lower Vm after apnea (44.3 ± 9.0 cm/s vs. 53.4 ± 11.4 cm/s; p = 0.003), higher PI (0.91 ± 0.26 vs. 0.76 ± 0.12; p = 0.000) and RI (0.58 ± 0.11 vs. 0.52 ± 0.06; p = 0.021). PDvasc group showed higher PI (0.98 vs. 0.76; p = 0.001) and higher frequency of altered cVR (72.2% vs. 42.2%; p = 0.004). There was a significant predominance of higher values on Fazekas scale in the PDvasc group. We found no difference between the Fazekas scale when comparing motor subtypes groups but there was a trend toward higher scores in the AR phenotype. TCCS, a cost-effective method, displayed impaired cVR in Parkinsonian patients with risk factors for CVD with higher degree of MRI leukoaraiosis. PD patients with the AR disease phenotype also presented impaired cVR on TCCS and greater functional impairment, although with just a trend to higher scores on MRI Fazekas.

Brief Report: Sex Differences in the Association Between Cerebrovascular Function and Cognitive Health in People Living With HIV in Urban China.

Cardiometabolic and cerebrovascular disease are strong independent contributors to cognitive impairment in people living with HIV. Data suggest that cardiovascular risk may play a greater role in cognitive health in women than in men with HIV. We performed a cross-sectional study of 104 participants with virologically suppressed HIV from 2 clinics in urban China. Participants underwent neuropsychological testing from which we calculated T scores globally and in 5 cognitive domains. We assessed cerebral vasoreactivity of the middle cerebral arteries in response to breath holding. We constructed linear regression models to determine associations between cerebrovascular and cognitive function overall and stratified by sex. Women were younger than men (48 versus 51 years, P = 0.053), had fewer years of education (9 years versus 12 years, P = 0.004), and fewer cardiometabolic risk factors (0 versus 1 factor, P = 0.008). In a model with all participants, cerebrovascular function was significantly associated with global cognition (2.74 higher T score per 1-point higher cerebral vasoreactivity [SE 1.30], P = 0.037). Cerebrovascular function remained significantly associated with global cognition among women (4.15 higher T score [SE 1.78], P = 0.028) but not men (1.70 higher T score [SE 1.74], P = 0.33). The relationships between cerebrovascular function and specific cognitive domains followed a similar pattern, with significant associations present among women but not men. Women with well-controlled HIV may be more vulnerable to the effect of cerebrovascular injury on cognitive health than men. Studies evaluating strategies to protect against cognitive impairment in people living with HIV should include adequate representation of women and stratification of analyses by sex.

Transcranial Doppler: A Beginning of a New Era for Stroke Diagnosis

Transcranial Doppler (TCD) is an intracranial neurovascular exam that provides a real-time, rapid, non-invasive ultrasound technique to analyze cerebrovascular function. It uses high-frequency sound waves to assess the blood flow velocity, detect the deficit that causes focal vascular stenosis, and diagnose the embolic signals inside these arteries. Moreover, it can be used to analyze particular vascular territory of physiologic health by measuring cerebral vasoreactivity, cerebral autoregulation, and functional hyperemia. The information obtained from these examinations is increasingly becoming pertinent for therapeutic decision-making. In this study, we are going to focus on a comparative analysis of TCD findings using clinical and other modalities and assess the specificity, sensitivity, and positive and negative predictive value of TCD findings in Asymptomatic and Symptomatic high-risk elderly patients. Furthermore, we will study the clinical usefulness of TCD in evaluating patients with cerebrovascular accidents (CVA).

Transcranial Doppler: A Beginning of a New Era for Stroke Diagnosis

Transcranial Doppler (TCD) is an intracranial neurovascular exam that provides a real-time, rapid, non-invasive ultrasound technique to analyze cerebrovascular function. It uses high-frequency sound waves to assess the blood flow velocity, detect the deficit that causes focal vascular stenosis, and diagnose the embolic signals inside these arteries. Moreover, it can be used to analyze particular vascular territory of physiologic health by measuring cerebral vasoreactivity, cerebral autoregulation, and functional hyperemia. The information obtained from these examinations is increasingly becoming pertinent for therapeutic decision-making. In this study, we are going to focus on a comparative analysis of TCD findings using clinical and other modalities and assess the specificity, sensitivity, and positive and negative predictive value of TCD findings in Asymptomatic and Symptomatic high-risk elderly patients. Furthermore, we will study the clinical usefulness of TCD in evaluating patients with cerebrovascular accidents (CVA).

Impairment of cerebral CO2 dynamic vasoreactivity in MCI &amp; AD patients: a multi‐center study of cerebral flow regulation

AbstractBackgroundAlzheimer’s Disease Centers in Los Angeles (USC), Dallas (UT‐SWMC) and Kansas City (KUMC) have joined together to study the regulation of cerebral perfusion through analysis of spontaneous time‐series data using a modeling methodology that previously yielded indications of reduced CO2 dynamic vasomotor reactivity (DVR) in amnestic MCI patients. We report initial results from this ongoing multi‐center study that confirm those preliminary findings and, furthermore, elucidate the effects of slow‐paced breathing.MethodFive‐minute spontaneous changes in arterial blood pressure (ABP), end‐tidal CO2 (etCO2) and cerebral blood flow velocity (CBFV) in middle cerebral arteries were obtained before and after 5‐min session of slow‐paced breathing (8 breaths/minute). Using data from 25 MCI patients, 7 AD patients and 45 age‐matched cognitively normal controls (NC), we obtained predictive models of the dynamic effects of ABP and etCO2 (proxy for blood CO2) upon CBFV via our kernel‐based modeling methodology. These predictive models were used to compute indices (physio‐markers) that quantify the DVR in each participant, as time‐average of the model‐predicted CBFV response to unit‐step change of etCO2 over the first 30 seconds.ResultThe obtained DVR indices were significantly different for the 32 patients (MCI and AD lumped together due to small number of AD) vs. 45 age‐matched controls (p= 0.0099). Notably, the delineation between patients and controls improved (p= 0.0011) after a 5‐min session of slow‐paced breathing. Figure 1 shows the average model‐predicted CBFV response to unit‐step change of etCO2 for 32 MCI/AD patients (red line) and 45 controls (blue line) before and after the 5‐min paced‐breathing session. Note the negative average steady‐state CBFV response of the patients (red) that indicates polarity reversal of the normal CO2 vasomotor reactivity (blue). Better delineation between patients and controls is achieved (p= 2x10‐5) when the DVR indices from the two sessions, before and after slow‐paced breathing, were averaged (see histograms in Figure 2).ConclusionSignificantly lower DVR indices under resting spontaneous conditions were observed in 32 MCI/AD patients relative to 45 age‐matched controls. This reduction is detected more reliably after 5‐min of slow‐paced breathing. Averaging of the DVR indices obtained before and after slow‐paced breathing improved further this delineation (p= 2x10‐5).

Three‐dimensional study on morphological changes of arterioles in Cerebral Amyloid Angiopathy

AbstractBackgroundThe accumulation of β‐amyloid plaques in the brain is a hallmark of Alzheimer’s disease. Vascular involvement is also common in the form of cerebral amyloid angiopathy (CAA), a vasculopathy that is produced when the β‐amyloid forms toxic deposits on vessels wall. The accumulation of β‐amyloid makes blood vessels stiff and increases the thickness of the vessel wall, reducing the blood flow and energy supply for the tissue. This predisposes to hemorrhage and contribute to cognitive decline and stroke.MethodWe used the CLARITY method to analyze tissue samples from patients with CAA to characterize changes to vessel morphology associated with vascular degeneration. The blood vessels were stained with isolectin, β‐amyloid with thiazine red, and proteins with primary antibodies associated with the vascular structure. We conducted 3D microscopy using a light sheet microscope and performed surface volume reconstruction to assess the morphology of rupturing vessel. We also measured arteriolar stiffness of vessels damaged using atomic force microscopy (AFM). Finally, we assessed cerebral blood flow and autoregulation in vivo in a novel mouse model of CAA using laser speckle flowetry.ResultVessels with CAA demonstrate an organized ring‐shaped deposits β‐amyloid. At sites, these rings are shattered and the vessel diameter increase. Degenerating vessels also demonstrate depletion of vascular smooth muscle, circumferential luminal dilation, and thickening of the vessel wall. Lysyl oxidase levels and markers of fibrosis are increased in vessels with degenerating features. We found that the arteriolar wall was more than 400% stiffer in CAA than in arterioles without CAA in the mice model. Finally, in a novel mouse model of CAA we are terming the VASC‐FAD model, resting cerebral blood flow and vasoreactivity are both reduced.ConclusionCombining the CLARITY technique associated with surface volume rendering and AFM we have a better overview of microhemorrhages to understand the vascular fragility and morphological changes, and accumulation of myofibroblast markers caused by the β‐amyloid deposition and stiffness. These features combine to alter the physiology of cerebral blood flow. Defining mechanism of microvascular degeneration in AD and CAA may lead to novel treatment targets to restore the ECM and vascular network integrity.

Changes in cerebral autoregulation and vasoreactivity after surgical aortic valve replacement: a prospective study.

What is the central question of this study? How are dynamic cerebral autoregulation and brain vasoreactivity influenced by severe aortic stenosis and its surgical treatment? What are the main findings and their importance? Dynamic cerebral autoregulation is preserved in the long term in patients with severe aortic stenosis and does not change after surgical aortic valve replacement. However, carbon dioxide vasoreactivity is impaired in these patients. Surgical aortic valve replacement (SAVR) alters the natural course of severe aortic stenosis (AS). In this study, we aimed to determine the effects of the disease on dynamic cerebral autoregulation and vasoreactivity (VR) and to assess their changes after SAVR. We recruited 23 patients diagnosed with severe AS eligible for SAVR and 15 healthy matched controls. AS patients had lower mean VR to CO2 (P=0.005) than controls, but dynamic cerebral autoregulation was preserved. Cerebral haemodynamics showed no significant change after SAVR. Patients with smaller baseline aortic valve areas presented with smaller low frequency phase changes after surgery (P=0.016). Severe AS does not seem to impact dynamic cerebral autoregulation but does reduce VR to CO2 . SAVR does not alter cerebral autoregulation nor vasoreactivity.

Cerebral Oxygen Delivery and Consumption in Brain-Injured Patients.

Organism survival depends on oxygen delivery and utilization to maintain the balance of energy and toxic oxidants production. This regulation is crucial to the brain, especially after acute injuries. Secondary insults after brain damage may include impaired cerebral metabolism, ischemia, intracranial hypertension and oxygen concentration disturbances such as hypoxia or hyperoxia. Recent data highlight the important role of clinical protocols in improving oxygen delivery and resulting in lower mortality in brain-injured patients. Clinical protocols guide the rules for oxygen supplementation based on physiological processes such as elevation of oxygen supply (by mean arterial pressure (MAP) and intracranial pressure (ICP) modulation, cerebral vasoreactivity, oxygen capacity) and reduction of oxygen demand (by pharmacological sedation and coma or hypothermia). The aim of this review is to discuss oxygen metabolism in the brain under different conditions.

Chronic Endothelial Dysfunction after COVID-19 Infection Shown by Transcranial Color-Coded Doppler: A Cross-Sectional Study.

In addition to respiratory symptoms, COVID-19 often causes damage to many other organs, especially in severe forms of the disease. Long-term consequences after COVID-19 are common and often have neurological symptoms. Cerebral vasoreactivity may be impaired after acute COVID-19 and in our study, we wanted to show how constant and reversible are the changes in brain vasoreactivity after infection. This cross-sectional observational study included 49 patients diagnosed with COVID-19 and mild neurological symptoms 300 days after the onset of the disease. We used a transcranial color-coded Doppler (TCCD) and a breath-holding test (BHT) to examine cerebral vasoreactivity and brain endothelial function. We analyzed the parameters of the flow rate through the middle cerebral artery (MCA): peak systolic velocity (PSV), end-diastolic velocity (EDV), mean velocity (MV), resistance index (RI) and pulsatility index (PI), and we calculated the breath-holding index (BHI). Subjects after COVID-19 infection had lower measured velocity parameters through MCA at rest period and after BHT, lower relative increases of flow velocities after BHT, and lower BHI. We showed that subjects, 300 days after COVID-19, still have impaired cerebral vasoreactivity measured by TCCD and they have chronic endothelial dysfunction.