Variations In Cerebral Blood Flow Research Articles

Detectability of Driver’s “Feeling of Excitement” and “Feeling of Nervousness” by Cerebral Blood Flow and Heart Rate Variability

Detectability of Driver’s “Feeling of Excitement” and “Feeling of Nervousness” by Cerebral Blood Flow and Heart Rate Variability

The Study of Cerebral Blood Flow Variations during Brain Metastases Radiotherapy

Purpose: The aim of this study was to investigate the cerebral blood flow (CBF) variations during brain metastases (BMs) radiotherapy (RT) applying with magnetic resonance (MR) 3D-arterial spin labeling (ASL). Materials and Methods: A total of 26 BM patients with 54 tumors were retrospectively enrolled. MR examinations were performed before and during RT (30–50 Gy) with a total dose of 36–60 Gy (12–30 fractions) including contrast-enhanced T1-weighted, T2 Flair, and 3D-ASL images. The relationship between CBF changes and the largest cross-sectional area changes in BMs was investigated. And CBF changes in BMs, normal brain tissue, and peritumoral edema areas were analyzed under different dose gradients that were divided into 10 Gy intervals. Results: The largest cross-sectional areas and CBF of 54 BMs decreased by 26.46% and 29.64%, respectively, during RT (p < 0.05), but there was no correlation between the 2 changes (p > 0.05). The rates of CBF decrease in BMs were 33.75%, 24.61%, and 27.55% at 30–40, 40–50, and >50 Gy, respectively (p < 0.05). In normal brain tissue with dose gradients of 0–10, 10–20, 20–30, 30–40, 40–50, and >50 Gy, the CBF decreased by 7.65%, 11.12%, 18.42%, 20.23%, 19.79%, and 17.89%, respectively (p < 0.05). The CBF decreases reached a maximum at 30–40 Gy in normal brain tissue as well as BMs. In contrast, the CBF decreases of peritumoral edema areas increased as the dose gradients increased. Moreover, the CBF changes of BMs were more notable than those in normal brain tissue and peritumoral edema areas. Conclusion: CBF changes can be feasibly assessed in different brain regions during RT based on 3D-ASL. The changes should be considered as a critical factor to determine the personal radiation dose for BMs, normal brain tissue, and peritumoral edema areas.

Spatial variation of perfusion MRI reflects cognitive decline in mild cognitive impairment and early dementia

Cerebral blood flow (CBF) measured with arterial spin labelling (ASL) magnetic resonance imaging (MRI) reflects cerebral perfusion, related to metabolism, and arterial transit time (ATT), related to vascular health. Our aim was to investigate the spatial coefficient of variation (sCoV) of CBF maps as a surrogate for ATT, in volunteers meeting criteria for subjective cognitive decline (SCD), amnestic mild cognitive impairment (MCI) and probable Alzheimer’s dementia (AD). Whole-brain pseudo continuous ASL MRI was performed at 3 T in 122 participants (controls = 20, SCD = 44, MCI = 45 and AD = 13) across three sites in New Zealand. From CBF maps that included all grey matter, sCoV progressively increased across each group with increased cognitive deficit. A similar overall trend was found when examining sCoV solely in the temporal lobe. We conclude that sCoV, a simple to compute imaging metric derived from ASL MRI, is sensitive to varying degrees of cognitive changes and supports the view that vascular health contributes to cognitive decline associated with Alzheimer’s disease.

Noninvasive Optical Measurements of Dynamic Cerebral Autoregulation by Inducing Oscillatory Cerebral Hemodynamics.

Objective: Cerebral autoregulation limits the variability of cerebral blood flow (CBF) in the presence of systemic arterial blood pressure (ABP) changes. Monitoring cerebral autoregulation is important in the Neurocritical Care Unit (NCCU) to assess cerebral health. Here, our goal is to identify optimal frequency-domain near-infrared spectroscopy (FD-NIRS) parameters and apply a hemodynamic model of coherent hemodynamics spectroscopy (CHS) to assess cerebral autoregulation in healthy adult subjects and NCCU patients.Methods: In five healthy subjects and three NCCU patients, ABP oscillations at a frequency around 0.065 Hz were induced by cyclic inflation-deflation of pneumatic thigh cuffs. Transfer function analysis based on wavelet transform was performed to measure dynamic relationships between ABP and oscillations in oxy- (O), deoxy- (D), and total- (T) hemoglobin concentrations measured with different FD-NIRS methods. In healthy subjects, we also obtained the dynamic CBF-ABP relationship by using FD-NIRS measurements and the CHS model. In healthy subjects, an interval of hypercapnia was performed to induce cerebral autoregulation impairment. In NCCU patients, the optical measurements of autoregulation were linked to individual clinical diagnoses.Results: In healthy subjects, hypercapnia leads to a more negative phase difference of both O and D oscillations vs. ABP oscillations, which are consistent across different FD-NIRS methods and are highly correlated with a more negative phase difference CBF vs. ABP. In the NCCU, a less negative phase difference of D vs. ABP was observed in one patient as compared to two others, indicating a better autoregulation in that patient.Conclusions: Non-invasive optical measurements of induced phase difference between D and ABP show the strongest sensitivity to cerebral autoregulation. The results from healthy subjects also show that the CHS model, in combination with FD-NIRS, can be applied to measure the CBF-ABP dynamics for a better direct measurement of cerebral autoregulation.

Cerebral and systemic hemodynamic effect of recurring seizures

The increase in neuronal activity induced by a single seizure is supported by a rise in the cerebral blood flow and tissue oxygenation, a mechanism called neurovascular coupling (NVC). Whether cerebral and systemic hemodynamics are able to match neuronal activity during recurring seizures is unclear, as data from rodent models are at odds with human studies. In order to clarify this issue, we used an invasive brain and systemic monitoring to study the effects of chemically induced non-convulsive seizures in sheep. Despite an increase in neuronal activity as seizures repeat (Spearman’s ρ coefficient 0.31, P < 0.001), ictal variations of cerebral blood flow remained stable while it progressively increased in the inter-ictal intervals (ρ = 0.06, P = 0.44 and ρ = 0.22; P = 0.008). We also observed a progressive reduction in the inter-ictal brain tissue oxygenation (ρ = − 0.18; P = 0.04), suggesting that NVC was unable to compensate for the metabolic demand of these closely repeating seizures. At the systemic level, there was a progressive reduction in blood pressure and a progressive rise in cardiac output (ρ = − 0.22; P = 0.01 and ρ = 0.22; P = 0.01, respectively), suggesting seizure-induced autonomic dysfunction.

Magnetic Resonance Imaging Reveals Significantly Increased Cerebral Blood Flow in the Hemoglobin E Mouse Model

Hemoglobin E (HbE) is the most common hemoglobin mutation world-wide. EE individuals exhibit a mild anemia as do those with β-thalassemia trait. A paradox arises with the combination of two relatively benign genes in HbE/β-thalassemia (HbE/β-thal) giving rise to highly morbid symptoms, anemia, growth retardation, developmental retardation, thalassemic bone type development, chronic leg ulcers (for a review, S Fucharoen and DJ Weatherall 2012) and often early mortality arising from cardiac failure (N Olivieri, Z Pakbaz et al. 2011). One approach to understanding the characteristics of HbE and this paradox was to generate a transgenic mouse model, expressing solely human HbE. This HbE mouse model exhibits a mild oxidative stress that parallels that observed in human EE individuals (QY Chen, EE Bouhassira et al. 2004, QY Chen, ME Fabry et al. 2012). These transgenic mice also exhibit mild cardiac dysfunction with depressed left ventricular contraction. We present here the first evidence of a significant increase in cerebral blood flow in the full knockout HbE (HbEKO) transgenic mouse model expressing solely human HbE compared to both the HbE+HbF (γ, gamma)-globin transgenic mouse, and the normal background C57 mouse. Cerebral blood flow is assessed non-invasively by MRI imaging. All protocols were approved by the Albert Einstein Institutional Animal Care and Use Committee.Comparing the HbEKO mouse (without human γ globin) to the C57 normal background mouse, a significant increase of over 20% in thalamus cerebral blood flow at baseline is observed (p=0.008). There is also an approximate 18% reduction in thalamus cerebral blood flow comparing HbE low γ mice to the full HbEKO (no γ) (p=0.011). Concomitant with these observations, no significant difference is observed comparing these low gamma HbE mice to the normal C57 background mouse (p=0.384). The goodness of the data is also seen in the relatively small variation in cerebral blood flow amongst the individual mice in each subset. These findings are of particular relevance to reports of neurologic symptoms, intracerebral hemorrhage, and brain infarct in HbE/β-thal patients (V Wong, YL Yu et al. 1990, S Das, S Dubey et al. 2019).In conclusion, these results suggest a direct role of HbE RBC initiating altered cerebral blood flow that when further complexed with β-thal could lead to intracerebral hemorrhage and other cerebral pathophysiology. The finding that the HbEKO mice with high HbF are not significantly different in cerebral blood flow from C57 mice may lend further support to therapeutic approaches enhancing the production of HbF in severe hemoglobinopathies, such as in sickle cell anemia, HbE/β-thal, and β-thal individuals. DisclosuresNo relevant conflicts of interest to declare.

Artefact subspace reconstruction for both EEG and fNIRS co-registred signals.

Combining electroencephalography (EEG) to functional near-infrared spectroscopy (fNIRS) is a promising technique that has gained momentum thanks to their complementarity. While EEG measures the electrical activity of the brain, fNIRS records the variations in cerebral blood flow and related hemoglobin concentrations. However, both modalities are typically contaminated with artefacts. Muscle and eye artefacts, affect the EEG signals, while hemodynamic and oxygenation changes in the extracerebral compartment due to systemic changes (superficial layer) corrupt the fNIRS signals. Moreover, both signals are sensitive to sensor motion artefacts characterized by large amplitude. There are several well-established methods for removing artefacts for both modalities. The objective of this paper is to apply a common approach to denoise both EEG and fNIRS signals. Indeed Artifact Subspace Reconstruction (ASR) method, which is an automatic, online-capable and efficient method for deleting transient or large-amplitude EEG artefacts, can be a good alternative to also denoise fNIRS signals. In this paper, we first propose, a new more comprehensive formulation of ASR. Then, we study the effectiveness of the method in denoising both the EEG and fNIRS signals.

Respiration is a Confounder of the Closed Loop Relationship Between Mean Arterial Pressure and Mean Cerebral Blood Flow.

This study tested the hypothesis that respiration (RESP) is a confounder or suppressor of the closed loop relationship responsible for the cerebrovascular dynamical interactions as assessed from spontaneous variability of mean arterial pressure (MAP) and mean cerebral blood flow (MCBF). The evaluation was carried out in the information domain via transfer entropy (TE) estimated through a linear model-based approach comparing TE markers computed solely over MAP and MCBF series with TE indexes accounting for the eventual action of RESP over MAP and MCBF. We considered 11 patients (age: 76±5 yrs, 7 males) undergoing surgical aortic valve replacement (SAVR) at supine resting (REST) and during active standing (STAND) before and after SAVR surgery. The decrease of the predictive ability of MCBF to MAP when accounting for RESP compared to the one assessed when disregarding RESP suggested that RESP is a confounder of the link from MCBF to MAP along the Cushing reflex instead of being a suppressor. This result was more evident in POST when autonomic control was dramatically depressed and in an unchallenged condition such as REST. RESP did not affect significantly the link from MAP to MCBF along the pressure-to-flow relationship. Clarification of the type of RESP influence on the MAP-MCBF closed loop relationship could favor a deeper characterization of cerebrovascular interactions and the comprehension of cerebral autoregulation mechanisms.Clinical Relevance- This study suggests that respiration is a confounder of the closed loop relationship between MAP and MCBF, especially of the flow-to-pressure causal link. This result might open new possibilities in elucidating the mechanisms of cerebral autoregulation in healthy and pathological populations.

Sensitivity of Arterial Spin Labeling for Characterization of Longitudinal Perfusion Changes in Frontotemporal Dementia and Related Disorders

BackgroundAdvances in the understanding of the pathophysiology of frontotemporal dementia (FTD) and related disorders, along with the development of novel candidate disease modifying treatments, have stimulated the need for tools to assess the efficacy of new therapies. While perfusion imaging by arterial spin labeling (ASL) is an attractive approach for longitudinal imaging biomarkers of neurodegeneration, sources of variability between sessions including arterial transit times (ATT) and fluctuations in resting perfusion can reduce its sensitivity. Establishing the magnitude of perfusion changes that can be reliably detected is necessary to delineate longitudinal perfusion changes related to disease processes from the effects of these sources of error. PurposeTo assess the feasibility of ASL for longitudinal monitoring of patients with FTD by quantifying between-session variability of perfusion on a voxel-by-voxel basis. Methods and materialsASL data were collected in 13 healthy controls and 8 patients with FTD or progressive supra-nuclear palsy. Variability in cerebral blood flow (CBF) by single delay pseudo-continuous ASL (SD-pCASL) acquired one month apart were quantified by the coefficient of variation (CV) and intraclass correlation coefficient (ICC). Additionally, CBF by SD-pCASL and ATT by low-resolution multiple inversion time ASL (LowRes-pCASL) were compared to Hadamard encoded sequences which are able to simultaneously measure CBF and ATT with improved time-efficiency. ResultsAgreement of grey-matter perfusion between sessions was found for both patients and controls (CV = 10.8% and 8.3% respectively) with good reliability for both groups (ICC > 0.6). Intensity normalization to remove day-to-day fluctuations in resting perfusion reduced the CV by 28%. Less than 5% of voxels had ATTs above the chosen post labelling delay (2 s), indicating that the ATT was not a significant source of error. Hadamard-encoded perfusion imaging yielded systematically higher CBF compared to SD-pCASL, but produced similar transit-time measurements. Power analysis revealed that SD-pCASL has the sensitivity to detect longitudinal changes as low as 10% with as few as 10 patient participants. ConclusionWith the appropriate labeling parameters, SD-pCASL is a promising approach for assessing longitudinal changes in CBF associated with FTD.

Effect of hematocrit on cerebral blood flow measured by pseudo-continuous arterial spin labeling MRI: A comparative study with 15O-water positron emission tomography

IntroductionIn cerebral blood flow (CBF) quantification with pseudo-continuous arterial spin labeling (pCASL) MRI, arterial blood T1 (T1a) is usually fixed to a typical value (e.g., 1650 ms). However, individual T1a depends strongly on hematocrit (Hct) level. To investigate the utility of Hct-based T1a as an alternative to the fixed T1a method, we performed a comparative study with 15O-water positron emission tomography (PET). MethodsFor patients with unilateral occlusion or stenosis of major arteries, hemispheric CBF on the healthy side was measured using pCASL and 15O-water PET. The pCASL CBFs were calculated with both (a) fixed T1a (1650 ms) and (b) individual T1a estimated from blood-sampled Hct (Hct-based T1a). Correlation coefficients of Hct–CBF were calculated and compared between pCASL and PET. ResultsIn pCASL, CBF with fixed T1a showed a strong negative correlation with Hct (r = −0.568), which was reduced with individual Hct-based T1a (r = −0.341 to −0.190), consistent with the Hct–CBF relation measured with PET (r = −0.349). Discussion and conclusionWe demonstrated that Hct-based T1a resulted in smaller inter-individual variations in pCASL CBF and an inverse Hct–CBF relationship more similar to that of PET. Care must be taken in the interpretation of pCASL CBF imaging in relation to Hct level even in subjects without anemia. Further comparative studies are needed to investigate whether advanced techniques improve pCASL CBF quantification at the individual level.

Early Warning Value of ASL-MRI to Estimate Premorbid Variations in Patients With Early Postoperative Cognitive Dysfunctions.

Background: Postoperative cognitive dysfunction (POCD) is a general complication following cardiac and major non-cardiac surgery amongst the elderly, yet its causes and mechanisms are still unknown. The present study aimed to detect whether regional cerebral blood flow (CBF) is altered in the brain before surgery in POCD patients compared with non-POCD (NPOCD) patients, thus, CBF variation may potentially predict the occurrence of early POCD.Methods: Fifty patients scheduled for spinal stenosis surgery were enrolled in the study. All study participants completed a battery of neuropsychological tests (NPTs) by a well-trained neuropsychologist before the surgery and 1 week after the surgery. POCD was defined when the preoperative to postoperative difference of at least two of the NPTs’ |Z|-scores with reference to a control group exceeded 1.96. Pulsed arterial spin-labeling (ASL) MRI was scanned at least 1 day before surgery. The ASLtbx toolkit and SPM12 were applied to preprocess and correct the images, which were then normalized to the MNI brain template space to obtain standardized cerebral perfusion images.Results: POCD was identified in 11 out of 50 patients (22%). The CBF of the right superior temporal lobe, right and left middle cingulate gyrus, and the right hippocampus, and parahippocampal gyrus in POCD group was lower than that in NPOCD group (P < 0.001). The CBF of the pars triangularis of inferior frontal gyrus in POCD group was higher than that in NPOCD group (P < 0.001).Conclusions: These preliminary findings suggest that CBF premorbid alterations may happen in cognitively intact elderly patients that develop early POCD. Alterations of preoperative CBF might be a bio-marker for early POCD that can be detected by noninvasive MRI scans.

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling

BackgroundMigraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine.MethodsThis study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated.ResultsIn comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R.ConclusionsOur results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.

Can 3D pseudo-continuous arterial spin labeling perfusion imaging be applied to predict early response to chemoradiotherapy in patients with advanced nasopharyngeal carcinoma?

Background and purposeChemoradiotherapy (CRT) has been widely applied in patients with advanced nasopharyngeal carcinoma (ANPC). However, limited imaging modality exists on the evaluation of early response to CRT. The purpose of this study was therefore to investigate whether 3D pseudo-continuous arterial spin labeling (3D pCASL) perfusion imaging could predict early response to CRT in ANPC patients. Materials and methodsSeventy ANPC patients who received CRT underwent pre-treatment MRI including 3D pCASL perfusion measurements, and were categorized into response group (RG) and no-response group (NRG) according to RECIST 1.1. Pre-treatment 3D pCASL derived cerebral blood flow (CBF) values in tumors were compared between RG and NRG patients. Receiver-operating characteristic (ROC) analysis was performed to determine the optimal diagnostic cutoff value for CBF in predicting tumor response to CRT. Clinicopathological variables were also analyzed by using univariate and binary logistic regression. The corresponding obtained variables with statistical significance were further applied to create a nomogram in which the bootstrap resampling method was used for calibration. ResultsForty-eight patients in RG had significantly higher pre-treatment CBF values in tumors compared with 22 patients in NRG (P < 0.001). CBF showed the high area under the ROC curve (AUC = 0.843) in distinguishing RG from NRG patients. The corresponding cutoff value for CBF was 103.68 ml/100 g/min, with respective accuracy, sensitivity and specificity of 82.86%, 87.50% and 72.73%. The nomogram was generated by binary logistic regression results, incorporating three variables: CBF value, clinical stage and pathological type. The AUC, accuracy, sensitivity and specificity of the nomogram was respectively 0.893, 84.28%, 81.25% and 90.91% in predicting tumor response to CRT. Moreover, as shown in the calibration curve, a strong agreement was observed between nomogram prediction probability and actual clinical findings (P = 0.309). Conclusions3D pCASL derived CBF in tumor could act as a noninvasive effective biomarker to predict tumor response to CRT in ANPC patients before clinical treatment. Furthermore, the nomogram combining CBF and clinicopathological variables could serve as a novel clinical analysis tool for treatment response prediction.

Cerebral Blood Flow Pulsatility Index is Unchanged during Superimposed Lower‐Body Negative Pressure in Head‐Up Tilt in Anterior and Posterior Cerebral Circulations

Lower body negative pressure (LBNP) chambers can be utilized to experimentally-elicit reductions in blood pressure, cerebral blood flow (CBF) and associated symptoms of presyncope. There is high between-individual variability in tolerance to LBNP, however the underlying physiological responses affecting tolerance remains unclear. Pulsatility in CBF may affect LBNP tolerance, as more pulsatile flow may protect the delivery of oxygen to cerebral tissues in hypotension. We aimed to assess the pulsatility index (PI) in anterior and posterior cerebral circulations during LBNP in superimposed head-up tilt (HUT), where gravitational-induced blood volume re-distribution augments volume unloading during LBNP. We recruited and included 12 healthy male participants, and instrumented them in a custom-build integrated 45° HUT-LBNP chamber. Participants were instrumented for heart rate (HR; ECG), end-tidal CO2 (PETCO2; mouthpiece and gas analyzer),beat-by-beat mean arterial pressure (MAP; finometer), and middle and posterior cerebral artery velocity (MCAv, PCAv; transcranial Doppler ultrasound). All measures were recorded during baseline (BL) and during -50 mmHg LBNP exposure up to a maximum of 10-minutes (600s). Presyncope was defined as a 30% reduction in systolic blood pressure (i.e., investigator stop) or onset subjective symptoms (i.e., participant stop). We quantified all variables as a 30-sec mean bin during BL and the final 30-sec of LBNP prior to presyncope. MAP, MCAv and PCAv PI was calculated as systolic-diastolic/mean. LBNP tolerance time was 480.9±134.3 sec. HR increased from 72.3±10.3 (BL) to 103.0±18.2 bpm (P<0.01) during LBNP, suggesting a baroreflex response, and PETCO2 was reduced from 32.0±2.9 (BL) to 28.7±2.9 Torr (P<0.01) during LBNP, suggesting mild hyperventilation. MAP decreased from 84.8±11.3 (BL) to 76.2±14.7 mmHg (P<0.01) during LBNP, with associated reductions in mean MCAv from 52.1±15.0 to 44.3±14.5 cm/s (P<0.01), and mean PCAv from 35.5±12.6 to 29.0±9.9 cm/s (P<0.01) during LBNP. MAP PI was reduced from 0.76±0.2 to 0.59±0.02 (P<0.01) during LBNP. However, MCAv and PCAv PI were unchanged during LBNP (P=0.6 and P=0.9, respectively). Our results suggest that although MAP and MAP PI were both reduced during LBNP at pre-syncope, with associated reductions in mean MCAv and PCAv, MCAv and PCAv PI remained stable with LBNP in HUT. These findings suggest that PI in CBF variables at the cardiac frequency are not related to LBNP tolerance in healthy men.

Osteopathy modulates brain\u2013heart interaction in chronic pain patients: an ASL study

In this study we used a combination of measures including regional cerebral blood flow (rCBF) and heart rate variability (HRV) to investigate brain–heart correlates of longitudinal baseline changes of chronic low back pain (cLBP) after osteopathic manipulative treatment (OMT). Thirty-two right-handed patients were randomised and divided into 4 weekly session of OMT (N = 16) or Sham (N = 16). Participants aged 42.3 ± 7.3 (M/F: 20/12) with cLBP (duration: 14.6 ± 8.0 m). At the end of the study, patients receiving OMT showed decreased baseline rCBF within several regions belonging to the pain matrix (left posterior insula, left anterior cingulate cortex, left thalamus), sensory regions (left superior parietal lobe), middle frontal lobe and left cuneus. Conversely, rCBF was increased in right anterior insula, bilateral striatum, left posterior cingulate cortex, right prefrontal cortex, left cerebellum and right ventroposterior lateral thalamus in the OMT group as compared with Sham. OMT showed a statistically significant negative correlation between baseline High Frequency HRV changes and rCBF changes at T2 in the left posterior insula and bilateral lentiform nucleus. The same brain regions showed a positive correlation between rCBF changes and Low Frequency HRV baseline changes at T2. These findings suggest that OMT can play a significant role in regulating brain–heart interaction mechanisms.

Lower cerebral perfusion is associated with tau-PET in the entorhinal cortex across the Alzheimer's continuum

Alzheimer's disease (AD) is associated with reduced temporo-parietal cerebral blood flow (CBF). However, a substantial variability in CBF across the clinical spectrum of AD has been reported, possibly due to differences in primary AD pathologies. Here, we assessed CBF (ASL-MRI), tau (AV1451-PET) and amyloid (AV45/FBB-PET) in 156 subjects across the AD continuum. Using mixed-effect regression analyses, we assessed the local associations between amyloid-PET, tau-PET and CBF in a hypothesis-driven way focusing on each pathology's predilection areas. The contribution of Apolipoprotein E (APOE) genotype, and MRI markers of small vessel disease (SVD) to alterations in CBF were assessed as well. Tau-PET was associated with lower CBF in the entorhinal cortex, independent of Aβ. Amyloid-PET was associated with lower CBF in temporo-parietal regions. No associations between MRI markers of SVD and CBF were observed. These results provide evidence that in addition to Aβ, pathologic tau is a major correlate of CBF in early Braak stages, independent of Aβ, APOE genotype and SVD markers.

Speckle contrast diffuse correlation tomography of cerebral blood flow in perinatal disease model of neonatal piglets.

We adapted and tested an innovative noncontact speckle contrast diffuse correlation tomography (scDCT) system for 3D imaging of cerebral blood flow (CBF) variations in perinatal disease models utilizing neonatal piglets, which closely resemble human neonates. CBF variations were concurrently measured by the scDCT and an established diffuse correlation spectroscopy (DCS) during global ischemia, intraventricular hemorrhage, and asphyxia; significant correlations were observed. Moreover, CBF variations associated reasonably with vital pathophysiological changes. In contrast to DCS measurements of mixed signals from local scalp, skull and brain, scDCT generates 3D images of CBF distributions at prescribed depths within the head, thus enabling specific determination of regional cerebral ischemia. With further optimization and validation in animals and human neonates, scDCT has the potential to be a noninvasive imaging tool for both basic neuroscience research in laboratories and clinical applications in neonatal intensive care units.

Short-term cerebral blood flow variability in major depressive disorder

BackgroundPrevious research has documented reduced heart rate and blood pressure variability in major depressive disorder (MDD), suggesting a limited capacity for cardiovascular regulation and diminished homeostatic resources in the disorder. This study aimed to complement this knowledge by investigating short-term cerebral blood flow (CBF) variability in MDD. MethodsUsing transcranial Doppler sonography, blood flow velocities in the middle cerebral arteries of both hemispheres were recorded in 35 MDD patients and 35 healthy controls, at rest and during serial subtraction task-induced mental stress. CBF variability was represented by the root mean square of successive differences (RMSSD) in the beat-to-beat mean, systolic and diastolic flow velocity. ResultsPatients, as compared to controls, exhibited smaller mean and diastolic blood flow variability in MCA both at rest and during mental stress. Mean, systolic and diastolic blood flow variability were greater during the task than at rest. CBF variability did not differ between patient subgroups composed according to medication use. LimitationsPotential effects of blood pressure and respiration on CBF variability could not be investigated. ConclusionsThe study revealed evidence of reduced short-term CBF variability in MDD. The task-induced CBF variability increase may be ascribed to neural activity associated with arithmetic processing. Lower blood pressure variability and deficient autonomic cardiovascular control may contribute to the reduction of short-term CBF variability seen in MDD. Short-term CBF variability reflects preserved interplay of regulatory mechanisms ensuring optimal blood and energy supply to the brain. Therefore, the results suggest impaired cerebroprotective mechanisms, associated with suboptimal cerebral performance.

Noncontact optical imaging of brain hemodynamics in preterm infants: a preliminary study

Extremely preterm infants’ hemodynamic instability places them at high risk of brain injury. Currently there is no reliable bedside method to continuously monitor cerebral hemodynamics in the neonatal intensive care unit (NICU). This paper reports a feasibility study to adapt and test an innovative speckle contrast diffuse correlation tomography (scDCT) device for noncontact, high-density, 3D imaging of cerebral blood flow (CBF) in preterm infants. The scDCT scans a focused point near-infrared illumination to multiple source positions for deep tissue penetration, and controls an electron multiplying charge-coupled-device camera with thousands of pixels to achieve a high-density sampling. The optimized scDCT for use in preterm infants was first evaluated against an established diffuse correlation spectroscopy in an infant-head-simulating phantom with known properties. The observed significant correlation between the two measurements verified the capability of scDCT for transcranial brain imaging. The insignificant influence of transparent incubator wall on scDCT measurements was then confirmed by comparing adult forearm blood flow responses to artery cuff occlusions measured inside and outside the incubator. Finally, the scDCT device was moved to the NICU to image CBF variations in two preterm infants. Infant #1 with no major organ deficits showed little CBF fluctuation over the first 3 weeks of life. Infant #2 showed a significant CBF increase after the 2 h pharmacotherapy for patent ductus arteriosus closure. While these CBF variations meet physiological expectations, the fact that no significant changes are noted with peripheral monitoring of blood oxygen saturation suggests necessity of direct cerebral monitoring. This feasibility study with timely technology development is an important and necessary step towards larger clinical studies with more subjects to further validate it for continuous monitoring and instant management of cerebral pathologies and interventions in the NICU.

Lower Thalamic Blood Flow Is Associated With Slower Stride Velocity in Older Adults.

BackgroundGait deficits are associated with brain atrophy and white matter hyperintensities (WMH) – both markers of underlying cerebral small vessel disease (SVD). Given reduced subcortical cerebral blood flow (CBF) is prevalent in SVD, we tested the hypothesis that regional CBF is positively associated with gait performance among older adults.MethodsThirty-two older adults (55–80 years) with at least one vascular risk factor were recruited. We assessed gait during 2 consecutive walking sequences using a GAITRite system: (1) at a self-selected pace, and (2) while performing a serial subtraction dual-task challenge. We quantified CBF using pseudo-continuous arterial spin labeling MRI within 4 regions of interest: putamen, pallidum, thalamus, and hippocampus. We investigated associations between gait characteristics and overall CBF adjusting for age, sex, and height in an omnibus approach using multivariate analysis of variance, followed by regression analysis with each individual region. We also conducted further regression analyses to investigate associations between gait characteristics and frontal lobe CBF. Sensitivity analyses examined how the observed associations were modified by WMH, executive function, and depressive symptoms. A change of 10% in the model’s adjusted r2 and effect size was considered as a threshold for confounding.ResultsOverall subcortical CBF was not associated with self-paced gait. When examining individual ROI, gait velocity was directly related to thalamic CBF (p = 0.026), and across all gait variables the largest effect sizes were observed in relation to thalamic CBF. In the dual-task condition, gait variables were not related to CBF in either the omnibus approach or individual multiple regressions. Furthermore, no significant associations were observed between frontal CBF and gait variables in either the self-paced or dual-task condition. Sensitivity analyses which were restricted to examine the association of velocity and thalamic CBF identified a cofounding effect of depressive symptoms which increased the effect size of the CBF-gait association by 12%.ConclusionSubcortical hypoperfusion, particularly in regions that comprise central input/output tracts to the cortical tissue, may underlie the association between gait deficits and brain aging.