A multi-site 99mTc-HMPAO SPECT study of cerebral blood flow in a community sample of patients with major depression.

Prior regional Cerebral Blood Flow (rCBF) studies in Major Depressive Disorder (MDD) have been limited by small, highly selective, non-representative samples that have yielded variable and poorly replicated findings. The aim of this study was to compare rCBF measures in a large, more representative community sample of adults with MDD and healthy control participants. This is a cross-sectional, retrospective multi-site cohort study in which clinical data from 338 patients 18-65 years of age with a primary diagnosis of MDD were retrieved from a central database for 8 privately owned, private-pay outpatient psychiatric centers across the United States. Two 99mTc-HMPAO SPECT brain scans, one at rest and one during performance of a continuous performance task, were acquired as a routine component of their initial clinical evaluation. In total, 103 healthy controls, 18-65 years old and recruited from the community were also assessed and scanned. Depressed patients had significantly higher rCBF in frontal, anterior cingulate, and association cortices, and in basal ganglia, thalamus, and cerebellum, after accounting for significantly higher overall CBF. Depression severity associated positively with rCBF in the basal ganglia, hippocampus, cerebellum, and posterior white matter. Elevated rCBF was especially prominent in women and older patients. Elevated rCBF likely represents pathogenic hypermetabolism in MDD, with its magnitude in direct proportion to depression severity. It is brain-wide, with disproportionate increases in cortical and subcortical attentional networks. Hypermetabolism may be a reasonable target for novel therapeutics in MDD.

Measuring global cerebrovascular pulsatility transmission using 4D flow MRI.

Pulse wave encephalopathy (PWE) is hypothesised to initiate many forms of dementia, motivating its identification and risk assessment. As candidate pulsatility based biomarkers for PWE, pulsatility index and pulsatility damping have been studied and, currently, do not adequately stratify risk due to variability in pulsatility and spatial bias. Here, we propose a locus-independent pulsatility transmission coefficient computed by spatially tracking pulsatility along vessels to characterise the brain pulse dynamics at a whole-organ level. Our preliminary analyses in a cohort of 20 subjects indicate that this measurement agrees with clinical observations relating blood pulsatility with age, heart rate, and sex, making it a suitable candidate to study the risk of PWE. We identified transmission differences between vascular regions perfused by the basilar and internal carotid arteries attributed to the identified dependence on cerebral blood flow, and some participants presented differences between the internal carotid perfused regions that were not related to flow or pulsatility burden, suggesting underlying mechanical differences. Large populational studies would benefit from retrospective pulsatility transmission analyses, providing a new comprehensive arterial description of the hemodynamic state in the brain. We provide a publicly available implementation of our tools to derive this coefficient, built into pre-existing open-source software.

Compact and cost-effective laser-powered speckle contrast optical spectroscopy fiber-free device for measuring cerebral blood flow.

Significance: In the realm of cerebrovascular monitoring, primary metrics typically include blood pressure, which influences cerebral blood flow (CBF) and is contingent upon vessel radius. Measuring CBF noninvasively poses a persistent challenge, primarily attributed to the difficulty of accessing and obtaining signal from the brain. Aim: Our study aims to introduce a compact speckle contrast optical spectroscopy device for noninvasive CBF measurements at long source-to-detector distances, offering cost-effectiveness, and scalability while tracking blood flow (BF) with remarkable sensitivity and temporal resolution. Approach: The wearable sensor module consists solely of a laser diode and a board camera. It can be easily placed on a subject's head to measure BF at a sampling rate of 80 Hz. Results: Compared to the single-fiber-based version, the proposed device achieved a signal gain of about 70 times, showed superior stability, reproducibility, and signal-to-noise ratio for measuring BF at long source-to-detector distances. The device can be distributed in multiple configurations around the head. Conclusions: Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing noninvasive cerebral monitoring technologies.

Collaterals and stroke reperfusion: Too few leads to too much.

Adequate reperfusion after ischemic stroke is a major determinant of functional outcome yet remains unpredictable and insufficient for most survivors. In this issue of Neuron, Binder et al.1 identify leptomeningeal collaterals (LMCs) in mice and human patients as a key factor in regulating reperfusion and hemorrhagic transformation following stroke.

Intracranial Pressure and Cerebral Hemodynamics in Infants Before and After Glenn Procedure.

OBJECTIVES: This prospective cohort study aimed to investigate changes in intracranial pressure (ICP) and cerebral hemodynamics in infants with congenital heart disease undergoing the Glenn procedure, focusing on the relationship between superior vena cava pressure and estimated ICP. DESIGN: A single-center prospective cohort study. SETTING: The study was conducted in a cardiac center over 4 years (2019-2022). PATIENTS: Twenty-seven infants with congenital heart disease scheduled for the Glenn procedure were included in the study, and detailed patient demographics and primary diagnoses were recorded. INTERVENTIONS: Transcranial Doppler (TCD) ultrasound examinations were performed at three time points: baseline (preoperatively), postoperative while ventilated (within 24-48 hr), and at discharge. TCD parameters, blood pressure, and pulmonary artery pressure were measured. MEASUREMENTS AND MAIN RESULTS: TCD parameters included systolic flow velocity, diastolic flow velocity (dFV), mean flow velocity (mFV), pulsatility index (PI), and resistance index. Estimated ICP and cerebral perfusion pressure (CPP) were calculated using established formulas. There was a significant postoperative increase in estimated ICP from 11 mm Hg (interquartile range [IQR], 10-16 mm Hg) to 15 mm Hg (IQR, 12-21 mm Hg) postoperatively (p = 0.002) with a trend toward higher CPP from 22 mm Hg (IQR, 14-30 mm Hg) to 28 mm Hg (IQR, 22-38 mm Hg) postoperatively (p = 0.1). TCD indices reflected alterations in cerebral hemodynamics, including decreased dFV and mFV and increased PI. Intracranial hemodynamics while on positive airway pressure and after extubation were similar. CONCLUSIONS: Glenn procedure substantially increases estimated ICP while showing a trend toward higher CPP. These findings underscore the intricate interaction between venous pressure and cerebral hemodynamics in infants undergoing the Glenn procedure. They also highlight the remarkable complexity of cerebrovascular autoregulation in maintaining stable brain perfusion under these circumstances.

Assessing changes in regional cerebral hemodynamics in adults with a high-density full-head coverage time-resolved near-infrared spectroscopy device.

Significance: Cerebral oximeters have the potential to detect abnormal cerebral blood oxygenation to allow for early intervention. However, current commercial systems have two major limitations: (1) spatial coverage of only the frontal region, assuming that surgery-related hemodynamic effects are global and (2) susceptibility to extracerebral signal contamination inherent to continuous-wave near-infrared spectroscopy (NIRS). Aim: This work aimed to assess the feasibility of a high-density, time-resolved (tr) NIRS device (Kernel Flow) to monitor regional oxygenation changes across the cerebral cortex during surgery. Approach: The Flow system was assessed using two protocols. First, digital carotid compression was applied to healthy volunteers to cause a rapid oxygenation decrease across the ipsilateral hemisphere without affecting the contralateral side. Next, the system was used on patients undergoing shoulder surgery to provide continuous monitoring of cerebral oxygenation. In both protocols, the improved depth sensitivity of trNIRS was investigated by applying moment analysis. A dynamic wavelet filtering approach was also developed to remove observed temperature-induced signal drifts. Results: In the first protocol (28±5 years; five females, five males), hair significantly impacted regional sensitivity; however, the enhanced depth sensitivity of trNIRS was able to separate brain and scalp responses in the frontal region. Regional sensitivity was improved in the clinical study given the age-related reduction in hair density of the patients (65±15 years; 14 females, 13 males). In five patients who received phenylephrine to treat hypotension, different scalp and brain oxygenation responses were apparent, although no regional differences were observed. Conclusions: The Kernel Flow has promise as an intraoperative neuromonitoring device. Although regional sensitivity was affected by hair color and density, enhanced depth sensitivity of trNIRS was able to resolve differences in scalp and brain oxygenation responses in both protocols.

[Vascular Anatomy of the Middle Cerebral Artery and Cerebral Large Vessel Occlusion].

The middle cerebral artery divides into the cortical and perforating branches that supply blood to the extensive cerebral cortex and basal ganglia. In addition to an understanding of the normal vessel diameter and length, endovascular physicians should be familiar with anatomical variations. Understanding the perfusion territory is important for accurate diagnosis of the disease type.

Capture of emotional responses under a simulated earthquake experience using near-infrared spectroscopy and virtual reality.

AIM: In a previous study, we reported that watching two-dimensional videos of earthquakes significantly reduced sympathetic nerve activity in healthy young adults. In the present study, we aimed to investigate the emotional responses to earthquakes using immersive virtual reality (VR), which can provide a more realistic experience. METHODS: In total, 24 healthy young adults (12 males, 21.4 ± 0.2 years old) participated. Participants were required to watch earthquake and neutral videos while wearing a head-mounted display and near-infrared spectroscopy (NIRS), during which physiological signals, including pulse rate and cerebral blood flow (CBF) in the dorsolateral prefrontal cortex, were measured. We also analyzed changes in sympathetic and parasympathetic indices and obtained seven emotion ratings: valence, arousal, dominance, fear, astonishment, anxiety, and panic. RESULTS: The VR earthquake videos evoked negative subjective emotions, and the pulse rate significantly decreased. Sympathetic nerve activity tended to decrease, whereas CBF in the left prefrontal cortex showed a slight increase, although this was not significant. CONCLUSIONS: This study showed that measurements combined with NIRS and immersive VR have the potential to capture emotional responses to different stimuli.

Albumin levels and cerebral collateral circulation in patients with acute ischemic stroke due to intracranial arteriosclerotic: A propensity score-matched analysis.

Cerebral collateral circulation (CC) is associated with the recurrence and severity of acute ischemic stroke (AIS), and early identification of poor CC is helpful for the prevention of AIS. In this study we evaluated the association between serum albumin levels and CC in AIS using logistic regression. Propensity score (PS) matching was used to eliminate the effect of confounders, and restricted cubic splines (RCS) were employed to explore potential nonlinear associations between albumin and CC. In unadjusted logistic regression analysis, lower albumin (OR = 0.85, 95% CI = 0.79-0.92) was associated with poor CC, and after adjusting for covariates, the odds of lower albumin for poor CC compared to good CC were 0.86 (95% CI = 0.79-0.94). In the PS cohort, the association of albumin with CC was consistent with those of the original cohort. RCS results showed a linear relationship between albumin and CC (P values of .006 and .08 for overall and nonlinear associations, respectively). The results of this study suggest that lower serum albumin is independently associated with an increased risk of poor CC, which may serve as an effective predictive indicator for poor CC in patients with severe intracranial atherosclerotic stenosis.

Test-retest reliability and time-of-day variations of perfusion imaging at rest and during a vigilance task.

Arterial spin-labeled perfusion and blood oxygenation level-dependent functional MRI are indispensable tools for noninvasive human brain imaging in clinical and cognitive neuroscience, yet concerns persist regarding the reliability and reproducibility of functional MRI findings. The circadian rhythm is known to play a significant role in physiological and psychological responses, leading to variability in brain function at different times of the day. Despite this, test-retest reliability of brain function across different times of the day remains poorly understood. This study examined the test-retest reliability of six repeated cerebral blood flow measurements using arterial spin-labeled perfusion imaging both at resting-state and during the psychomotor vigilance test, as well as task-induced cerebral blood flow changes in a cohort of 38 healthy participants over a full day. The results demonstrated excellent test-retest reliability for absolute cerebral blood flow measurements at rest and during the psychomotor vigilance test throughout the day. However, task-induced cerebral blood flow changes exhibited poor reliability across various brain regions and networks. Furthermore, reliability declined over longer time intervals within the day, particularly during nighttime scans compared to daytime scans. These findings highlight the superior reliability of absolute cerebral blood flow compared to task-induced cerebral blood flow changes and emphasize the importance of controlling time-of-day effects to enhance the reliability and reproducibility of future brain imaging studies.

Aberrant cerebral blood flow and functional connectivity in patients with vestibular migraine: a resting-state ASL and fMRI study.

BACKGROUND: Prior neuroimaging studies on vestibular migraine (VM) have extensively certified the functional and structural alterations in multiple brain regions and networks. However, few studies have assessed the cerebral blood flow (CBF) in VM patients using arterial spin labeling (ASL). The present study aimed to investigate CBF and functional connectivity (FC) alterations in VM patients during interictal periods. METHODS: We evaluated 52 VM patients and 46 healthy controls (HC) who received resting-state pseudo-continuous ASL and functional magnetic resonance imaging (fMRI) scanning. Comparisons of voxel-based CBF and seed-based FC were performed between the two groups. Brain regions showed significant group differences in CBF analyses were chosen as seeds in FC analyses. Additionally, the associations between abnormal imaging results and clinical features were explored. RESULTS: Compared with HC, VM patients showed higher normalized CBF in the right precentral gyrus (PreCG), left postcentral gyrus (PostCG), left superior frontal gyrus and bilateral insular (p < 0.05, FDR corrected). Furthermore, VM patients exhibited increased FC between the right PreCG and areas of the left PostCG, left cuneus and right lingual gyrus (p < 0.05, FDR corrected). In addition, we observed decreased FC between the left insular and regions of the left thalamus and right anterior cingulate cortex, as well as increased FC between the left insular and right fusiform gyrus in VM patients (p < 0.05, FDR corrected). Moreover, these variations in brain perfusion and FC were significantly correlated with multiple clinical features including frequency of migraine symptoms, frequency of vestibular symptoms and disease duration of VM (all p < 0.05). CONCLUSIONS: Patients with VM during interictal period showed hyperperfusion and abnormal resting-state FC in brain regions potentially contributed to disrupted multi-sensory and autonomic processing, as well as impaired ocular motor control, pain modulation and emotional regulation. Our study provided novel insights into the complex neuropathology of VM from a CBF perspective.

Brain perfusion changes in beta-thalassemia.

BACKGROUND: Brain injury in hereditary hemoglobinopathies is commonly attributed to anemia-related relative hypoperfusion in terms of impaired oxygen blood supply. Supratentorial and infratentorial vascular watershed regions seem to be especially vulnerable, but data are very scarce. AIMS: We investigated a large beta-thalassemia sample with arterial spin labeling in order to characterize regional perfusion changes and their correlation with phenotype and anemia severity. METHODS: We performed a multicenter single-scanner cross-sectional 3T-MRI study analyzing non-invasively the brain perfusion in 54 transfusion-dependent thalassemia (TDT), 23 non-transfusion-dependent thalassemia (NTDT) patients and 56 Healthy Controls (HC). Age, hemoglobin levels, and cognitive functioning were recorded. RESULTS: Both TDT and NTDT patients showed globally increased brain perfusion values compared to healthy controls, while no difference was found between patient subgroups. Using age and sex as covariates and scaling the perfusion maps for the global cerebral blood flow, beta-thalassemia patients showed relative hyperperfusion in supratentorial/infratentorial watershed regions. Perfusion changes correlated with hemoglobin levels (p = 0.013) and were not observed in the less severely anemic patients (hemoglobin level > 9.5 g/dL). In the hyperperfused regions, white matter density was significantly decreased (p = 0.0003) in both patient subgroups vs. HC. In NTDT, white matter density changes correlated inversely with full-scale Intelligence Quotient (p = 0.007) while in TDT no correlation was found. CONCLUSION: Relative hyperperfusion of watershed territories represents a hemodynamic hallmark of beta-thalassemia anemia challenging previous hypotheses of brain injury in hereditary anemias. A careful management of anemia severity might be crucial for preventing structural white matter changes and subsequent long-term cognitive impairment.

Bilateral Prefrontal Cortex Blood Flow Dynamics during Silent and Oral Reading Using Near-Infrared Spectroscopy.

This study aimed to investigate blood flow dynamics in the bilateral prefrontal cortex during silent and oral reading using near-infrared spectroscopy (NIRS). The subjects were 40 right-handed university students (20.5±1.8 years old, 20 men and 20 women). After completing the NIRS measurements, the subjects were asked to rate their level of proficiency in silent and oral reading, using a 5-point Likert scale. During oral reading, the left lateral prefrontal cortex (Broca's area) was significantly more active than the right side. During silent reading, prefrontal cortex activity was lower than that during oral reading, and there was no significant difference between both sides of the brain. A significant negative correlation was found between the change in oxy-hemoglobin (oxy-Hb) concentration in the left and right lateral prefrontal cortex during silent reading and silent reading speed. In addition, students with lower self-reported reading proficiency had significantly greater changes in oxy-Hb concentrations in the left and right lateral prefrontal cortex during silent/oral reading than did students with higher self-reported reading proficiency. Reading task assessment using NIRS may be useful for identifying language lateralization and Broca's area. The results demonstrate that NIRS is useful for assessing effortful reading and may be used to diagnose developmental dyslexia in children. J. Med. Invest. 71 : 92-101, February, 2024.

Cerebral autoregulation: A reliable predictor of prognosis in patients receiving intravenous thrombolysis.

AIMS: To investigate the characteristics of dynamic cerebral autoregulation (dCA) after intravenous thrombolysis (IVT) and assess the relationship between dCA and prognosis. METHODS: Patients with unilateral acute ischemic stroke receiving IVT were prospectively enrolled; those who did not were selected as controls. All patients underwent dCA measurements, by quantifying the phase difference (PD) and gain, at 1-3 and 7-10 days after stroke onset. Simultaneously, two dCA-based nomogram models were established to verify the predictive value of dCA for patients with mild-to-moderate stroke. RESULTS: Finally, 202 patients who received IVT and 238 who did not were included. IVT was positively correlated with higher PD on days 1-3 and 7-10 after stroke onset. PD values in both sides at 1-3 days after stroke onset and in the affected side at 7-10 days after onset were independent predictors of unfavorable outcomes in patients who received IVT. Additionally, in patients with mild-to-moderate stroke who received IVT, the dCA-based nomogram models significantly improved the risk predictive ability for 3-month unfavorable outcomes. CONCLUSION: IVT has a positive effect on dCA in patients with acute stroke; furthermore, dCA may be useful to predict the prognosis of patients with IVT.

Retrograde cerebral perfusion reduces embolic and watershed lesions after acute type a aortic dissection repair with deep hypothermic circulatory arrest.

BACKGROUND: To assess whether retrograde cerebral perfusion reduces neurological injury and mortality in patients undergoing surgery for acute type A aortic dissection. METHODS: Single-center, retrospective, observational study including all patients undergoing acute type A aortic dissection repair with deep hypothermic circulatory arrest between January 1998 and December 2022 with or without the adjunct of retrograde cerebral perfusion. 515 patients were included: 257 patients with hypothermic circulatory arrest only and 258 patients with hypothermic circulatory arrest and retrograde cerebral perfusion. The primary endpoints were clinical neurological injury, embolic lesions, and watershed lesions. Multivariable logistic regression was performed to identify independent predictors of the primary outcomes. Survival analysis was performed using Kaplan-Meier estimates. RESULTS: Clinical neurological injury and embolic lesions were less frequent in patients with retrograde cerebral perfusion (20.2% vs. 28.4%, p = 0.041 and 13.7% vs. 23.4%, p = 0.010, respectively), but there was no significant difference in the occurrence of watershed lesions (3.0% vs. 6.1%, p = 0.156). However, after multivariable logistic regression, retrograde cerebral perfusion was associated with a significant reduction of clinical neurological injury (OR: 0.60; 95% CI 0.36-0.995, p = 0.049), embolic lesions (OR: 0.55; 95% CI 0.31-0.97, p = 0.041), and watershed lesions (OR: 0.25; 95%CI 0.07-0.80, p = 0.027). There was no significant difference in 30-day mortality (12.8% vs. 11.7%, p = ns) or long-term survival between groups. CONCLUSION: In this study, we showed that the addition of retrograde cerebral perfusion during hypothermic circulatory arrest in the setting of acute type A aortic dissection repair reduced the risk of clinical neurological injury, embolic lesions, and watershed lesions.

Transcranial volumetric imaging using a conformal ultrasound patch.

Accurate and continuous monitoring of cerebral blood flow is valuable for clinical neurocritical care and fundamental neurovascular research. Transcranial Doppler (TCD) ultrasonography is a widely used non-invasive method for evaluating cerebral blood flow1, but the conventional rigid design severely limits the measurement accuracy of the complex three-dimensional (3D) vascular networks and the practicality for prolonged recording2. Here we report a conformal ultrasound patch for hands-free volumetric imaging and continuous monitoring of cerebral blood flow. The 2 MHz ultrasound waves reduce the attenuation and phase aberration caused by the skull, and the copper mesh shielding layer provides conformal contact to the skin while improving the signal-to-noise ratio by 5 dB. Ultrafast ultrasound imaging based on diverging waves can accurately render the circle of Willis in 3D and minimize human errors during examinations. Focused ultrasound waves allow the recording of blood flow spectra at selected locations continuously. The high accuracy of the conformal ultrasound patch was confirmed in comparison with a conventional TCD probe on 36 participants, showing a mean difference and standard deviation of difference as -1.51 ± 4.34 cm s-1, -0.84 ± 3.06 cm s-1 and -0.50 ± 2.55 cm s-1 for peak systolic velocity, mean flow velocity, and end diastolic velocity, respectively. The measurement success rate was 70.6%, compared with 75.3% for a conventional TCD probe. Furthermore, we demonstrate continuous blood flow spectra during different interventions and identify cascades of intracranial B waves during drowsiness within 4 h of recording.

Early localization of tissue at risk for delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: blood distribution on initial imaging vs early CT perfusion.

OBJECTIVE: Delayed cerebral ischemia (DCI) is a potentially reversible adverse event after aneurysmal subarachnoid hemorrhage (aSAH), when early detected and treated. Computer tomography perfusion (CTP) is used to identify the tissue at risk for DCI. In this study, the predictive power of early CTP was compared with that of blood distribution on initial CT for localization of tissue at risk for DCI. METHODS: A consecutive patient cohort with aSAH treated between 2012 and 2020 was retrospectively analyzed. Blood distribution on CT was semi-quantitatively assessed with the Hijdra-score. The vessel territory with the most surrounding blood and the one with perfusion deficits on CTP performed on day 3 after ictus were considered to be at risk for DCI, respectively. RESULTS: A total of 324 patients were included. Delayed infarction occurred in 17% (56/324) of patients. Early perfusion deficits were detected in 82% (46/56) of patients, 85% (39/46) of them developed infarction within the predicted vessel territory at risk. In 46% (25/56) a vessel territory at risk was reliably determined by the blood distribution. For the prediction of DCI, blood amount/distribution was inferior to CTP. Concerning the identification of "tissue at risk" for DCI, a combination of both methods resulted in an increase of sensitivity to 64%, positive predictive value to 58%, and negative predictive value to 92%. CONCLUSIONS: Regarding the DCI-prediction, early CTP was superior to blood amount/distribution, while a consideration of subarachnoid blood distribution may help identify the vessel territories at risk for DCI in patients without early perfusion deficits.

Orbital doppler ultrasound as an ancillary test for diagnosing brain death: A prospective, single blind comparative study.

OBJECTIVE: Transcranial Doppler ultrasound (TDUS), computed tomography angiography (CTA), and transcranial Doppler ultrasound to detect cerebral blood flow are among the adjunctive tests in diagnosing brain death. This study aimed to investigate the effectiveness of orbital doppler ultrasound (ODUS). METHODS: This prospective, single-blind study included 66 patients for whom brain death was to be diagnosed. Primary outcome measures were ODUS measurements, Ophthalmic artery peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistive indices (RI) measurements recorded during the brain death determination process. Secondary outcome measures were computed tomography angio (CTA), transcranial Doppler ultrasound (TDUS), and demographic data. RESULTS: This study investigating the effectiveness of ODUS in diagnosing brain death provided diagnostic success with 100% sensitivity and 93% specificity compared to CT angiography. It was noted that anatomical variations may limit its use. CONCLUSION: ODUS was found to have high sensitivity and specificity in the diagnosis of clinical brain death. It may assist in early prognostic assessment and shorten patient follow-up and diagnostic processes.