Cerebral Artery Pulsatility Research Articles

Middle Cerebral Artery Pulsatility Index for Prediction of Successful Induction of Labour in Postdated Pregnancy: A Prospective Observational Study

Introduction: Postdated pregnancy is the most frequent indication for Induction of Labour (IOL). The foetal Middle Cerebral Artery Pulsatility Index (MCA PI) is assessed to predict foetal wellbeing in cases of late foetal growth restriction. It has also been studied as a predictor of IOL and is reported to be more sensitive than the conventional Bishop score. Aim: To evaluate the MCA PI as a predictor of successful labour induction in postdated pregnancy. Materials and Methods: This prospective observational study was conducted in obstetrics wards of Safdarjung Hospital over a period of 15 months, including 296 nulliparous women with singleton postdated pregnancy admitted for IOL. After obtaining a detailed history and conducting a physical examination, per vaginal examination for Bishop’s score and transabdominal ultrasound for foetal MCA Doppler was done. Women were followed for progression to active labour, and mode of delivery was noted. Primary outcome measure was successful IOL, defined as women entering active phase of labour, which is defined as cervical dilation of >5 cm. Other outcome measures studied included the induction to active phase interval, induction to delivery interval and mode of delivery. Receiver Operating Characteristics (ROC) curve was used to find out Area Under Curve (AUC) for MCA PI and Bishop score for predicting successful IOL. De Long et al., test was used to compare AUC. Univariate and multivariate logistic regression was used to assess the predictors of successful labour induction. A p-value of <0.05 was considered statistically significant. Results: Out of 296 women enrolled in the study, 285 women (96.3%) had successful IOL. Around 281 (98.9%) women with successful IOL had a vaginal delivery. At a cut-off of <1.67, MCA PI had a sensitivity of 100%, a specificity of 99.3%, a Positive Predictive Value (PPV) of 84.6%, a Negative Predictive Value (NPV) of 100%, and diagnostic accuracy of 99.3%, for prediction of successful IOL. MCA PI had almost perfect reliability for predicting the outcome of labour induction, Kappa=0.91 and Youden index score of 99.3. Conclusion: MCA PI is a good predictor of successful labour induction in nulliparous women with postdated pregnancy

Randomized Trial of Pulsatile and Nonpulsatile Flow in Cyanotic and Acyanotic Congenital Heart Surgery.

The study objective was to determine the impact of cardiopulmonary bypass perfusion modalities on cerebral hemodynamics and clinical outcomes in congenital cardiac surgery patients stratified by acyanotic versus cyanotic heart disease. A total of 159 pediatric (age <18 years) cardiac surgery patients were prospectively randomized to pulsatile or nonpulsatile cardiopulmonary bypass and stratified by type of congenital heart disease: acyanotic versus cyanotic. Intraoperative cerebral gaseous microemboli counts and middle cerebral artery pulsatility index were assessed. Organ injury was quantified by Pediatric Logistic Organ Dysfunction-2 (PELOD-2) score at 24, 48, and 72 h postoperatively. Additional outcomes included Pediatric Risk of Mortality-3 score, vasoactive-inotropic score, duration of mechanical ventilation, intensive care and hospital length of stay, and 180-day mortality. Heterogenous variance linear models (ie, ANOVA and mixed models) and χ2 tests were used to compare groups for continuous and categorical variables, respectively. Within congenital heart disease subgroups, patients randomized to nonpulsatile versus pulsatile bypass had similar preoperative and operative characteristics. While the intraoperative pulsatility index was higher in the pulsatile subset of both acyanotic and cyanotic groups (P < .05), regional cerebral oxygen saturation, mean arterial pressure, and gaseous microemboli counts were similar. Postoperative PELOD-2 scores decreased at similar rates in the acyanotic and cyanotic subgroups regardless of the perfusion modality utilized. There were also no significant between-group differences in the additional postoperative outcomes by perfusion modality in either acyanotic or cyanotic groups. Despite patients undergoing pulsatile cardiopulmonary bypass experiencing a more physiologic pulsatility index in both acyanotic and cyanotic groups, no significant differences in cerebral hemodynamics or clinical outcomes were appreciated.

Loss of glymphatic homeostasis in heart failure.

Heart failure (HF) is associated with progressive reduction in cerebral blood flow (CBF) and neurodegenerative changes leading to cognitive decline. The glymphatic system is crucial for the brain's waste removal, and its dysfunction is linked to neurodegeneration. In this study, we used a mouse model of HF, induced by myocardial infarction (MI), to investigate the effects of HF with reduced ejection fraction on the brain's glymphatic function. Using dynamic contrast-enhanced MRI and high-resolution fluorescence microscopy, we found increased solute influx from the CSF spaces to the brain, i.e. glymphatic influx, at 12 weeks post MI. Two-photon microscopy revealed that cerebral arterial pulsatility, a major driver of the glymphatic system, was potentiated at this timepoint, and could explain this increase in glymphatic influx. However, clearance of proteins from the brain parenchyma did not increase proportionately with influx, while a relative increase in brain parenchyma volume was found at 12 weeks post MI, suggesting dysregulation of brain fluid dynamics. Additionally, our results showed a correlation between brain clearance and CBF. These findings highlight the role of CBF as a key regulator of the glymphatic system, suggesting its involvement in the development of brain disorders associated with reduced CBF. This study paves the way for future investigations into the effects of cardiovascular diseases on the brain's clearance mechanisms, which may provide novel insights into the prevention and treatment of cognitive decline.

Abstract 4126358: Fetal cardiac physiology but not cerebrovascular resistance predicts neurodevelopmental outcomes in congenital heart disease

Introduction: Fetal “brain sparing” autoregulatory mechanisms respond to reduced cardiac output or substrate delivery by decreasing cerebrovascular resistance to maintain cerebral blood flow. In patients with congenital heart disease (CHD), data are conflicting on the association between fetal cerebral Doppler measures and postnatal neurodevelopment, possibly due to the heterogeneity of fetal cardiac physiology. Aim: To evaluate whether fetal cerebrovascular resistance estimated by middle cerebral artery pulsatility index (MCA PI) and cerebroplacental ratio (CPR; MCA PI divided by umbilical artery PI) predict neurodevelopment in patients with CHD. Methods: This retrospective analysis of a prospectively-enrolled cohort included cases with isolated CHD and healthy controls with a family history of CHD. Cases were classified by fetal cardiac physiology: single vs. biventricular circulation, outflow obstruction (none, systemic, pulmonary), and cerebral substrate delivery (normal, mixed, abnormal). Subjects underwent fetal echocardiography with cerebral and umbilical doppler measures (normalized for gestational age) as well as neurodevelopmental evaluation at two years of age with the Bayley Scales of Infant and Toddler Development III and IV. Results: Fetal echocardiograms and neurodevelopmental testing were obtained in 82 cases and 48 controls. There was no difference in MCA PI or CPR between cases and controls; however cases with mixed vs. normal substrate delivery had lower z-scores for MCA PI (-1.08 + 1.16 vs. -0.43 + 1.38, p=0.05) and CPR (-0.74 + 0.62 vs. -0.37 + 0.59, p=0.02). Cases had lower Bayley scores across all composite domains: cognitive (97.8 + 11.8 vs. 103.4 + 14.7, p=0.03), language (97.6 + 15.6 vs. 105.6 + 21.3, p=0.03), and motor (94.0 + 10.7 vs. 100.4 + 10.9, p=0.003). MCA PI and CPR were not associated with Bayley scores in cases or in sub-group analysis by fetal cardiac physiology. In multivariable analyses of Bayley scores adjusting for medical and demographic data, lower motor composite score was predicted by mixed vs. normal substrate delivery (partial R2=12.4%, p&lt;0.001) and single ventricle physiology (partial R2=6.5%, p=0.008). Conclusions: In patients with CHD, fetal single ventricle physiology with mixed substrate delivery was associated with worse motor development. The lack of association of fetal cerebral dopplers with neurodevelopment may suggest that decreased cerebrovascular resistance is not necessarily an effective compensatory mechanism in CHD.

Prenatal exposure to per- and polyfluoroalkyl substances, fetoplacental hemodynamics, and fetal growth

IntroductionThe impact of legacy per- and polyfluoroalkyl substances (PFAS) on fetal growth has been well studied, but assessments of next-generation PFAS and PFAS mixtures are sparse and the potential role of fetoplacental hemodynamics has not been studied. We aimed to evaluate associations between prenatal PFAS exposure and fetal growth and fetoplacental hemodynamics. MethodsWe included 747 pregnant women from the BiSC birth cohort (Barcelona, Spain (2018–2021)). Twenty-three PFAS were measured at 32 weeks of pregnancy in maternal plasma, of which 13 were present above detectable levels. Fetal growth was measured by ultrasound, as estimated fetal weight at 32 and 37 weeks of gestation, and weight at birth. Doppler ultrasound measurements for uterine (UtA), umbilical (UmA), and middle cerebral artery (MCA) pulsatility indices (PI), as well as the cerebroplacental ratio (CPR – ratio MCA to UmA), were obtained at 32 weeks to assess fetoplacental hemodynamics. We applied linear mixed effects models to assess the association between singular PFAS and longitudinal fetal growth and PI, and Bayesian Weighted Quantile Sum models to evaluate associations between the PFAS mixture and the aforementioned outcomes, controlled for the relevant covariates. ResultsSingle PFAS and the mixture tended to be associated with reduced fetal growth and CPR PI, but few associations reached statistical significance. Legacy PFAS PFOS, PFHpA, and PFDoDa were associated with statistically significant decreases in fetal weight z-score of 0.13 (95%CI (−0.22, −0.04), 0.06 (−0.10, 0.01), and 0.05 (−0.10, 0.00), respectively, per doubling of concentration. The PFAS mixture was associated with a non-statistically significant 0.09 decrease in birth weight z-score (95%CI −0.22, 0.04) per quartile increase. ConclusionThis study suggests that legacy PFAS may be associated with reduced fetal growth, but associations for next generation PFAS and for the PFAS mixture were less conclusive. Associations between PFAS and fetoplacental hemodynamics warrant further investigation.

Foetal cerebral blood redistribution in idiopathic polyhydramnios and the impact on perinatal outcomes

Background Idiopathic polyhydramnios is associated with adverse neonatal outcome. The aim of this study was to examine the value of the middle cerebral artery pulsatility index (MCA-PI) in predicting adverse perinatal outcome in pregnancies affected by idiopathic polyhydramnios. Methods A retrospective study was performed during 2013–2022 at a tertiary-care university affiliated hospital. The study included singleton pregnancies with idiopathic polyhydramnios. Obstetrical and perinatal outcomes were compared between women with MCA-PI <10th percentile and women with MCA-P ≥ 10th percentile. A composite adverse perinatal outcome was defined as an Apgar score <7 at 5 minutes, umbilical artery pH <7.15, emergent caesarean delivery (CD) or operative delivery due to foetal distress, neonatal intensive care admission or foetal death. Results Among 45,459 pregnancies, 128 (0.3%) had idiopathic polyhydramnios; 27 exhibited MCA-PI <10th percentile. Among the latter, compared to pregnancies with MCA-PI ≥10th percentile group, the rates were higher of emergent CD (25.9% vs. 7.9%, p = 0.017) and adverse perinatal outcomes (37.0% vs. 15.8%, p = 0.020). These differences persisted in a subgroup analysis of women with moderate or severe polyhydramnios. In the MCA-PI <10th percentile group, the median MCA-PI and cerebroplacental ratio were lower: 0.9 vs. 1.7, p < 0.001 and 0.7 vs. 2.1, p < 0.001, respectively. Receiver operating characteristic curve analysis indicated a significant association of MCA-PI with emergent CD/operative delivery for foetal distress (area under curve = 0.672, p = 0.031); the sensitivity was 46.7% and specificity 82.3%. Cerebroplacental ratio values were not associated with adverse perinatal outcomes. Conclusions Idiopathic polyhydramnios might be associated with foetal cerebral blood flow redistribution, potentially contributing to an increased risk of adverse neonatal outcomes. Prospective studies are required to establish the role of foetal Doppler studies in the antenatal surveillance of idiopathic polyhydramnios, and to determine whether evidence of abnormal MCA-PI serves as a reliable predictor of perinatal outcomes, potentially necessitating labour induction.

Role of Transcranial Doppler Ultrasound in Early Assessment of Acute Post Traumatic Brain Injury

Abstract Introduction Traumatic brain injury (TBI) is a global health and socioeconomic problem. It is responsible of millions of ED visits, hospitalizations, and deaths with lifelong disability among survivors. Immediately after TBI, cerebral blood flow (CBF) is extremely low approaching the ischemic thresholds. Concurrently, CBF velocities become strongly correlated to CBF itself. Identification of such disturbances can predict outcome in TBI when assessed early post- injury using Transcranial Doppler (TCD). TCD provides non-invasive real time measurements of CBF velocities as well as pulsatility index (PI). Design Observational prospective cohort study. Setting Helwan university hospital. Aim to assess the accuracy of transcranial Doppler ultrasound as an early predictor of secondary neurological deterioration after acute post traumatic brain injury Patients and Methods 55 patients of acute post traumatic brain injury underwent TCD within 8 hours post trauma. Middle cerebral artery (MCA) velocities and pulsatility index, as well as GCS and initial CT findings, were recorded. The primary end point was the development of secondary neurological deterioration (SND) at day 7 after injury. Secondary outcome measures were the in-hospital mortality and hospital length of stay. Results There was a significant relation between end diastolic velocity (EVD) as well as PI with SND at day 7 as well as GOSE at day 28 post-trauma. There was also significant correlation between PI and hospital mortality. Conclusion TCD, when done early after admission, is useful in identifying patients at risk for developing neurological deterioration after TBI. EDV and PI are good predictors of SND at one week.as well as in-hospital mortality.

Foramen Ovale Pulsatility Index as an Early Affected Doppler Study among Abnormal Growth Fetuses: A Recent Insight for Practice Based on a Prospective Study.

Routine Doppler study is a common tool for early diagnosis of Fetal Growth Restriction (FGR) and Small for Gestational Age (SGA) patients. It aimed to determine the role of the Foramen Ovale Pulsatility Index (FOPI) study beside routine Doppler study among patients with FGR and SGA fetuses. This prospective study was conducted on 35 FGR, 32 SGA, and 33 Appropriate for Gestational Age (AGA) fetuses. Demographic data, amniotic fluid index, neonatal outcome, and Doppler velocimetry, including Umbilical Artery Pulsatility Index (UMAPI), Uterine Artery Pulsatility Index (UTAPI), Middle Cerebral Artery Pulsatility Index (MCAPI), Ductus Venosus Pulsatility Index (DVPI), and FOPI were documented. Kolmogorov-Smirnov normality test, one-way ANOVA, Mann-Whitney U, Kruskal-Wallis, non-parametric pairwise comparisons adjusted for Bonferroni correction, Pearson correlation test, Chi square, Fisher's exact test, and Receiver Operating Characteristic Curve (ROC) analysis with Youden's Index (sensitivity+specificity-1) to estimate cut-off point were used to analyze the data at significance level <0.05 for all tests. FOPI cut-off points were 2.24 (sensitivity=77%, specificity=94%) and 1.15 (sensitivity=90%, specificity=20%) to predict FGR and SGA, respectively. FOPI showed a positive correlation with UMAPI and UTAPI (r=0.52 and r=0.30, P<0.001 and P=0.006, respectively), but not with MCAPI and DVPI (r=0.08 and r=0.12, P=0.50 and P=0.30, respectively). Besides, UMAPI, UTAPI, and FOPI were altered among patients with stages I and II FGR. Umbilical cord potential hydrogen (umbilical cord pH), 1- and 5-min Apgar score significantly increased by Birth weight centile; however, UMAPI, FOPI, and UTAPI significantly decreased. UMAPI is recommended to predict short-term neonatal morbidities and demonstrate the early or late onset FGR. Besides, FOPI is suggested as the first-line Doppler study to detect abnormal growth velocity. More studies are warranted, especially considering long-term neonatal morbidities.

Safety and feasibility pilot study of continuous low-dose maternal supplemental oxygen in fetal single ventricle heart disease.

Fetuses with single ventricle physiology (SVP) exhibit reductions in fetal cerebral oxygenation, with associated delays in fetal brain growth and neurodevelopmental outcomes. Maternal supplemental oxygen (MSO) has been proposed to improve fetal brain growth, but current evidence on dosing, candidacy and outcomes is limited. In this pilot study, we evaluated the safety and feasibility of continuous low-dose MSO in the setting of SVP. This single-center, open-label, pilot phase-1 safety and feasibility clinical trial included 25 pregnant individuals with a diagnosis of fetal SVP. Participants self-administered continuous MSO using medical-grade oxygen concentrators for up to 24 h per day from the second half of gestation until delivery. The primary aim was the evaluation of the safety profile and feasibility of MSO. A secondary preliminary analysis was performed to assess the impact of MSO on the fetal circulation using echocardiography and late-gestation cardiovascular magnetic resonance imaging. Early outcomes were assessed, including perinatal growth and preoperative brain injury, and neurodevelopmental outcomes were assessed at 18 months using the Bayley Scales of Infant and Toddler Development 3rd edition, and compared with those of a contemporary fetal SVP cohort (n = 217) that received the normal standard of care (SOC). Among the 25 participants, the median maternal age at conception was 35 years, and fetal SVP diagnoses included 16 with right ventricle dominant, eight with left ventricle dominant and one with indeterminate ventricular morphology. Participants started the trial at approximately 29 + 2 weeks' gestation and self-administered MSO for a median of 16.1 h per day for 63 days, accumulating a median of 1029 h of oxygen intake from enrolment until delivery. The only treatment-associated adverse events were nasal complications that were resolved typically by attaching a humidifier unit to the oxygen concentrator. No premature closure of the ductus arteriosus or unexpected fetal demise was observed. In the secondary analysis, MSO was not associated with any changes in fetal growth, middle cerebral artery pulsatility index, cerebroplacental ratio or head-circumference-to-abdominal-circumference ratio Z-scores over gestation compared with SOC. Although MSO was associated with changes in umbilical artery pulsatility index Z-score over the study period compared with SOC (P = 0.02), this was probably due to initial baseline differences in placental resistance. At late-gestation cardiovascular magnetic resonance imaging, MSO was not associated with an increase in fetal cerebral oxygen delivery. Similarly, no differences were observed in neonatal outcomes, including preoperative brain weight Z-score and brain injury, mortality by 18 months of age and neurodevelopmental outcomes at 18 months of age. This pilot phase-1 clinical trial indicates that low-dose MSO therapy is safe and well tolerated in pregnancies diagnosed with fetal SVP. However, our protocol was not associated with an increase in fetal cerebral oxygen delivery or improvements in early neurological or neurodevelopmental outcomes. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Using Doppler ultrasound to assess fetal cardiac function and pregnancy outcomes in obstetric antiphospholipid syndrome pregnancies: a case-control study.

This study aimed to evaluate fetal left ventricular function (LVF) in pregnant women with obstetric antiphospholipid syndrome (OAPS) by Doppler ultrasound and developed a clinical nomogram to predict adverse perinatal outcomes. In this prospective observational study, 105 pregnant women were enrolled and divided into the OAPS cohort (n = 60) and the control cohort (n = 45). Fetal cardiac function parameters were collected and compared between two cohorts. Univariate and multivariate analysis was conducted to select the risk factors associated with adverse perinatal outcomes, and a clinical nomogram was developed based on these selected risk factors. The predictive performance of corresponding indicators for adverse perinatal outcomes was evaluated using receiver operating characteristic (ROC) curve analysis. The OAPS cohort revealed an increase in the isovolumic relaxation time (IVRT) and myocardial performance index (MPI), a decrease in the ejection time (ET), middle cerebral artery pulsatility index (MCA-PI) and cerebroplacental ratio (CPR) compared to the control cohort. Through univariate and multivariate analysis, gravidity, CPR, and MPI were the risk factors associated with adverse perinatal outcomes. A model predicting adverse perinatal outcomes in OAPS pregnant women was constructed based on these three factors and visualized as a nomogram. The nomogram could accurately predict adverse perinatal outcomes with an area under the curve of 0.923 (95% CI: 0.858-0.982). This performance was better than evaluating individual factors such as MPI (0.825, 95% CI: 0.739-0.911) and CPR (0.816, 95% CI: 0.705-0.927) for efficacy. MPI can be used to assess fetal LVF and predict adverse perinatal outcomes. We developed a nomogram to predict adverse perinatal outcomes in OAPS women. This imaging-based evidence can provide timely clinical intervention, enabling personalized clinical decision-making.

The role of the cerebro-placental-uterine ratio in predicting composite adverse perinatal outcomes in patients with pregnancy-induced hypertension

ObjectivesTo examine the role of the cerebro-placental-uterine ratio (CPUR) in predicting composite adverse perinatal outcomes (CAPO) in patients with pregnancy-induced hypertension (PIH). Study designThis prospective, case-control study was conducted at a tertiary hospital with 110 cases of PIH, including 70 patients with preeclampsia and 40 with gestational hypertension, and 110 healthy controls. The middle cerebral artery pulsatility index (MCA-PI), umbilical artery pulsatility index (UA-PI), and uterine artery pulsatility index (UtA-PI) were measured, and the cerebro-placental ratio (CPR=MCA-PI/UA-PI) and CPUR (CPR/UtA-PI) were calculated. Main outcome measureThe role of CPUR in predicting CAPO in preeclampsia and gestational hypertension. ResultsThe CPR and CPUR values were lower in the PIH group compared to the control group (p < 0.001). CAPO had a negative correlation with CPR and CPUR (p < 0.001). Univariate regression analysis revealed that the likelihood of CAPO was increased four times by a low CPR value and six times by a low CPUR value. In the ROC analysis, the optimal cut-off value of CPR in predicting CAPO was 1.33 with 74 % sensitivity and 66 % specificity (area under the curve [AUC] = 0.778; p < 0.001) in PIH. For CPUR, the optimal cut-off value was 1.32, at which 82 % sensitivity and 79 % specificity in predicting CAPO (AUC=0.826; p < 0.001). ConclusionCPUR was determined to be successful with high sensitivity in predicting adverse perinatal outcomes in the presence of PIH. In addition, CPUR was more effective in predicting CAPO in patients with preeclampsia compared to gestational hypertension. CPUR can be used to predict adverse outcomes in patients with PIH.

Prevalence of Abnormal Cerebroplacental Ratio in Uncomplicated Full-term Pregnancy and Correlation with Adverse Perinatal Outcomes

Objective: To investigate the prevalence of abnormal cerebroplacental ratio (CPR) and predicting values for adverse perinatal outcomes in uncomplicated full-term pregnancies. Materials and Methods: This prospective cross-sectional study was conducted at Bhumibol Adulyadej Hospital, Royal Thai Air Force, Thailand between July and December 2023. The study population comprised pregnant women between the ages 18 and 45 presenting uncomplicated full-term pregnancies. Transabdominal ultrasonography in Doppler color mode was performed on all participants. Umbilical artery pulsatility index (UAPI) and middle cerebral artery pulsatility index (MCAPI) were both measured. CPR was calculated by MCAPI divided by UAPI. A CPR value was considered low if it was less than 1.03. Obstetric and perinatal outcomes were recorded including route of delivery, gestational age (GA) at delivery, obstetric complications, Apgar score, neonatal birth weight, neonatal intensive care unit (NICU) admission, and fetal non-reassuring tracing (FNR). Results: A total of 250 pregnant women were recruited. The mean maternal age and GA was 27.7 years, 39.6 weeks, respectively. Low CPR prevalence was recorded at 16.4 percent. There were 41 and 209 cases in low (&lt;1.03) and normal (≥1.03) CPR groups, respectively. UAPI and MCAPI of the normal/low CPR group were 0.8/1.3 and 1.1/0.9 with statistical significance. CPR for predicted value of FNR (1.03) gave sensitivity, specificity, PPV, and NPV at 95.5, 91.2, 51.2 and 99.5 percent, respectively. This study presented no adverse perinatal outcomes. Conclusion: Low CPR prevalence was 16.4 percent. Normal CPR values measured within a week before birth was a good indicator of normal perinatal outcomes.

Blood–brain barrier integrity is linked to cognitive function, but not to cerebral arterial pulsatility, among elderly

Blood–brain barrier (BBB) disruption may contribute to cognitive decline, but questions remain whether this association is more pronounced for certain brain regions, such as the hippocampus, or represents a whole-brain mechanism. Further, whether human BBB leakage is triggered by excessive vascular pulsatility, as suggested by animal studies, remains unknown. In a prospective cohort (N = 50; 68–84 years), we used contrast-enhanced MRI to estimate the permeability-surface area product (PS) and fractional plasma volume (vp\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${v}_{p}$$\\end{document}), and 4D flow MRI to assess cerebral arterial pulsatility. Cognition was assessed by the Montreal Cognitive Assessment (MoCA) score. We hypothesized that high PS would be associated with high arterial pulsatility, and that links to cognition would be specific to hippocampal PS. For 15 brain regions, PS ranged from 0.38 to 0.85 (·10−3 min−1) and vp\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${v}_{p}$$\\end{document} from 0.79 to 1.78%. Cognition was related to PS (·10−3 min−1) in hippocampus (β = – 2.9; p = 0.006), basal ganglia (β = – 2.3; p = 0.04), white matter (β = – 2.6; p = 0.04), whole-brain (β = – 2.7; p = 0.04) and borderline-related for cortex (β = – 2.7; p = 0.076). Pulsatility was unrelated to PS for all regions (p > 0.19). Our findings suggest PS–cognition links mainly reflect a whole-brain phenomenon with only slightly more pronounced links for the hippocampus, and provide no evidence of excessive pulsatility as a trigger of BBB disruption.

Cerebrovascular Effects of Sildenafil in Small Vessel Disease: The OxHARP Trial.

Vascular cognitive impairment due to cerebral small vessel disease is associated with cerebral pulsatility, white matter hypoperfusion, and reduced cerebrovascular reactivity (CVR), and is potentially improved by endothelium-targeted drugs such as cilostazol. Whether sildenafil, a phosphodiesterase-5 inhibitor, improves cerebrovascular dysfunction is unknown. OxHARP trial (Oxford Haemodynamic Adaptation to Reduce Pulsatility) was a double-blind, randomized, placebo-controlled, 3-way crossover trial after nonembolic cerebrovascular events with mild-moderate white matter hyperintensities (WMH), the most prevalent manifestation of cerebral small vessel disease. The primary outcome assessed the superiority of 3 weeks of sildenafil 50 mg thrice daily versus placebo (mixed-effect linear models) on middle cerebral artery pulsatility, derived from peak systolic and end-diastolic velocities (transcranial ultrasound), with noninferiority to cilostazol 100 mg twice daily. Secondary end points included the following: cerebrovascular reactivity during inhalation of air, 4% and 6% CO2 on transcranial ultrasound (transcranial ultrasound-CVR); blood oxygen-level dependent-magnetic resonance imaging within WMH (CVR-WMH) and normal-appearing white matter (CVR-normal-appearing white matter); cerebral perfusion by arterial spin labeling (magnetic resonance imaging pseudocontinuous arterial spin labeling); and resistance by cerebrovascular conductance. Adverse effects were compared by Cochran Q. In 65/75 (87%) patients (median, 70 years;79% male) with valid primary outcome data, cerebral pulsatility was unchanged on sildenafil versus placebo (0.02, -0.01 to 0.05; P=0.18), or versus cilostazol (-0.01, -0.04 to 0.02; P=0.36), despite increased blood flow (∆ peak systolic velocity, 6.3 cm/s, 3.5-9.07; P<0.001; ∆ end-diastolic velocity, 1.98, 0.66-3.29; P=0.004). Secondary outcomes improved on sildenafil versus placebo for CVR-transcranial ultrasound (0.83 cm/s per mm Hg, 0.23-1.42; P=0.007), CVR-WMH (0.07, 0-0.14; P=0.043), CVR-normal-appearing white matter (0.06, 0.00-0.12; P=0.048), perfusion (WMH: 1.82 mL/100 g per minute, 0.5-3.15; P=0.008; and normal-appearing white matter, 2.12, 0.66-3.6; P=0.006) and cerebrovascular resistance (sildenafil-placebo: 0.08, 0.05-0.10; P=4.9×10-8; cilostazol-placebo, 0.06, 0.03-0.09; P=5.1×10-5). Both drugs increased headaches (P=1.1×10-4), while cilostazol increased moderate-severe diarrhea (P=0.013). Sildenafil did not reduce pulsatility but increased cerebrovascular reactivity and perfusion. Sildenafil merits further study to determine whether it prevents the clinical sequelae of small vessel disease. URL: https://www.clinicaltrials.gov/study/NCT03855332; Unique identifier: NCT03855332.

Sonographic evaluation of intracranial hemodynamics and pressure after out-of-hospital cardiac arrest: An exploratory sub-study of the TAME trial

ObjectiveTargeted mild hypercapnia is a potential neuroprotective therapy after cardiac arrest. In this exploratory observational study, we aimed to explore the effects of targeted mild hypercapnia on cerebral microvascular resistance assessed by middle cerebral artery pulsatility index (MCA PI) and intracranial pressure estimated by optic nerve sheath diameter (ONSD) in resuscitated out-of-hospital cardiac arrest (OHCA) patients. Design, setting, participants and interventionsComatose adults resuscitated from OHCA were randomly allocated to targeted mild hypercapnia (PaCO2 50–55 mmHg) or targeted normocapnia (PaCO2 35–45 mmHg) for 24 h in the TAME trial. Main outcome measuresUsing transcranial Doppler and transorbital ultrasound, we obtained MCA PI and ONSD at 4, 24, and 48 h after randomization. Ultrasound parameters were compared between groups using a linear mixed effects model. ResultsTwelve consecutive patients were included, with seven patients in the mild hypercapnia group. MCA PI decreased from 4 to 24 h (p = 0.019) and was lower over the first 24 h in patients allocated to targeted mild hypercapnia compared with targeted normocapnia (p = 0.047). ONSD did not differ between groups or over time. ConclusionCerebral microvascular resistance assessed by MCA PI decreased over 24 h and was lower in OHCA patients treated with targeted mild hypercapnia compared with targeted normocapnia. Targeted mild hypercapnia did not exert substantial effect on intracranial pressure as estimated by ONSD.

Multimodal Neurologic Monitoring in Patients Undergoing Extracorporeal Membrane Oxygenation.

Introduction Extracorporeal membrane oxygenation (ECMO) is associated with a high rate of neurologic complications. Multimodal neurologic monitoring (MNM) has the potential for early detection and intervention. We examined the safety and feasibility of noninvasive MNM during ECMO. We hypothesized that survivors and non-survivors would have meaningful differences in transcranial Doppler (TCD) sonography and electroencephalographic (EEG) characteristics, which we aimed to identify. We also investigated adverse neurologic events and attempted to identify differences in EEG and TCD characteristics among patients based on the type of ECMO and the occurrence of these events. Material and methods We performed an observational study on all patients undergoing ECMO at Baylor St. Luke's Medical Center's critical care unit in Houston, Texas, United States, from January 2017 to February 2019. All patients underwent a noninvasive MNM protocol. Results NM was completed in 75% of patients; all patients received at least one component of the monitoring protocol. No adverse events were noted, showing the feasibility and safety of the protocol. The 60.4% of patients who did not survive tended to be older, had lower ejection fractions, and had lower median right middle cerebral artery (MCA) pulsatility and resistivity indexes. Patients undergoing venoarterial (VA)-ECMO had lower median left and right MCA velocities and lower right Lindegaard ratios than patients who underwent venovenous-ECMO. In VA-ECMO patients, EEG less often showed sleep architecture, while other findings were similar between groups. Adverse neurologic events occurred in 24.7% of patients, all undergoing VA-ECMO. Acute ischemic stroke occurred in 22% of patients, intraparenchymal hemorrhage in 4.9%, hypoxic-ischemic encephalopathy in 3.7%, subarachnoid hemorrhage in 2.5%, and subdural hematoma in 1.2%. Conclusion Our results suggest that MNM is safe and feasible for patients undergoing ECMO. Certain EEG and TCD findings could aid in the early detection of neurologic deterioration. MNM may not just be used in monitoring patients undergoing ECMO but also in prognostication and aiding clinical decision-making.

Associations Between Grip Strength and Cerebral Hemodynamics in Young and Middle-Aged Adults

Aerobic fitness and aerobic exercise are widely accepted as having protective effects on cognitive function and brain health, with less understood regarding muscular fitness and resistance exercise. Strength is beneficially associated with cognitive function, but the mechanisms underlying this relationship remain understudied and may relate to cerebral hemodynamics. The purpose of this study was to examine the associations between strength and cerebrovascular hemodynamics in young and middle-aged men and women. It was hypothesized that greater strength would be associated with better cerebral hemodynamics (greater mean blood velocity, lower pulsatility, greater pulsatile damping). Ninety-two generally healthy adults between 18-64 years old (36±16 yrs; BMI 25.9±4.0 kg/m2; n=39 women) underwent a hand grip strength assessment and resting cerebrovascular measures. Grip strength was measured via dynamometer and recorded as the highest value of 3 attempts. Middle cerebral artery (MCA) mean velocity and pulsatility index (PI) were measured via transcranial Doppler. Pulsatile damping was calculated as the ratio between the common carotid artery and MCA PI. Mean arterial pressure was assessed via an oscillometric blood pressure cuff. No significant associations were observed between relative grip strength and MCA mean velocity (r=-0.15), MCA PI (r=0.05), or MAP (r=0.07) after adjusting for age. Greater relative grip strength, however, was associated with greater pulsatile damping after adjusting for age (r=0.21; p&lt;0.05). This relationship appeared to be driven by weak associations within each sex (men, r=0.10; women, r=0.02) that were not statistically significant on their own. Our preliminary results suggest there are no strong relations between grip strength and cerebral hemodynamics among generally healthy young and middle-aged adults after accounting for the effects of age and sex. Future studies should examine sex-specific associations with a larger sample, consider disease states related to cerebrovascular health, and include more comprehensive assessments of muscular strength and performance (e.g., power). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Cerebroplacental ratio and perinatal outcomes in mild-to-moderate idiopathic polyhydramnios cases.

This study will evaluate whether fetal cerebroplacental ratio (CPR) can predict perinatal adverse outcomes in singleton pregnancies with mild and moderate idiopathic polyhydramnios (IP). This study was designed as a prospective case-control study between January 2023 and November 2023. Pregnant women diagnosed with mild-to-moderate IP and low-risk singleton pregnancies were included in the study. In all cases, umbilical artery (UA) and middle cerebral artery (MCA) pulsatility indices (PIs) were measured at 36-40 weeks of gestation, and CPR was calculated. The group with polyhydramnios was divided into two parts according to whether the CPR value was below 1.08 or 1.08 and above. Perinatal outcomes of all groups were compared. A total of 140 patients were included in the study. Seventy of these were IP cases, and 70 were low-risk pregnant women. UA PI in the IP group was not statistically different from that in the low-risk group, but MCA PI and CPR were significantly lower in the IP group (P = 0.07, P = 0.001, and P = 0.004, respectively). IP cases were divided into a low group (<1.08, n = 18) and a normal group (≥1.08, n = 52) according to the CPR value. Cesarean section rates due to fetal distress were significantly higher in the low-CPR group (n = 8 [44.4%] vs 5 [9.6%], P = 0.001). In the low-CPR group, 5-min Apgar <7, and neonatal intensive care unit (NICU) admission rates were significantly higher (P = 0.045 and P = 0.001, respectively). It is encouraging that in cases with mild-to-moderate IP, low CPR predicts emergency delivery due to fetal distress, a low Apgar score at 5 min, and NICU admission.

Feasibility and preliminary efficacy of a theory-informed resistance exercise training single-arm intervention for major depression

Many adults with major depressive disorder (MDD) do not receive effective treatment. The potential benefits of resistance exercise training (RET) are understudied and may be mechanistically related to cerebral blood flow changes. PurposeTo assess feasibility, acceptability, and preliminary efficacy of a 16-week, theory-informed RET trial for the treatment of MDD and explore changes in cerebral blood flow. MethodsTen adults with DSM-5-diagnosed MDD were enrolled in a single-arm, 16-week, twice-weekly, whole-body RET intervention, consistent with US and WHO Physical Activity resistance exercise guidelines. To build intrinsic motivation and develop exercise-preparatory habits, motivators and commitment were discussed weekly. Screening, enrollment, and intervention attendance and compliance rates documented feasibility. At baseline and weeks 8, 16, and 26, current MDD diagnosis, clinician-rated, and self-reported symptom severity were evaluated along with cerebral blood flow which was assessed as middle cerebral artery (MCA) mean blood velocity, conductance, and pulsatility. ResultsNine participants completed the intervention. Strong feasibility and acceptability (98 % adherence, 93 % compliance, and 90 % retention) were found. MDD remission was reached by 8/9 participants at week 16 and persisted through week 26. There were large decreases in clinician-rated and self-reported symptoms at each assessment (Hedges’ g = 0.84–2.13). There were small-to-moderate increases in MCA velocity (g = 0.32–0.57) and conductance (g = 0.20–0.76) across time, with minimal changes in pulsatility (all g < 0.21). ConclusionsPreliminary results suggest RET for MDD treatment is feasible and plausibly efficacious, finding large antidepressant effects. A sufficiently powered randomized controlled trial to assess RET’s efficacy for treating MDD via potential cerebrovascular mechanisms is warranted.

Effects of aerobic exercise training on cerebral pulsatile hemodynamics in middle-aged adults with elevated blood pressure/stage 1 hypertension.

Mechanisms behind the protective effects of aerobic exercise on brain health remain elusive but may be vascular in origin and relate to cerebral pulsatility. This pilot study investigated the effects of 12-wk aerobic exercise training on cerebral pulsatility and its vascular contributors (large artery stiffness, characteristic impedance) in at-risk middle-aged adults. Twenty-eight inactive middle-aged adults with elevated blood pressure or stage 1 hypertension were assigned to either moderate/vigorous aerobic exercise training (AET) for 3 days/wk or no-exercise control (CON) group. Middle cerebral artery (MCA) pulsatility index (PI), large artery (i.e., aorta, carotid) stiffness, and characteristic impedance were assessed via Doppler and tonometry at baseline, 6, and 12 wk, whereas cardiorespiratory fitness (V̇o2peak) was assessed via incremental exercise test and cognitive function via computerized battery at baseline and 12 wk. V̇o2peak increased 6% in AET and decreased 4% in CON (P < 0.05). Proximal aortic compliance increased (P = 0.04, partial η2 = 0.14) and aortic characteristic impedance decreased (P = 0.02, partial η2 = 0.17) with AET but not CON. Cerebral pulsatility showed a medium-to-large effect size increase with AET, although not statistically significant (P = 0.07, partial η2 = 0.11) compared with CON. Working memory reaction time improved with AET but not CON (P = 0.02, partial η2 = 0.20). Our data suggest 12-wk AET elicited improvements in central vascular hemodynamics (e.g., proximal aortic compliance and characteristic impedance) along with apparent, paradoxical increases in cerebral pulsatile hemodynamics.NEW & NOTEWORTHY We identify differential central versus cerebrovascular responses to 12 wk of aerobic exercise training in middle-aged adults. Although proximal aortic compliance and characteristic impedance improved after 12 wk of exercise, cerebral pulsatility tended to unexpectedly increase. These data suggest short-term aerobic exercise training may lead to more immediate benefits in the central vasculature, whereas longer duration exercise training may be required for beneficial changes in pulsatility within the cerebrovasculature.