Cerebral Blood Flow Measurements Research Articles

I feel your pain: higher empathy is associated with higher posterior default mode network activity

Abstract Empathy is characterized as the ability to share one's experience and is associated with altruism. Previous work using blood oxygen level–dependent (BOLD) functional MRI (fMRI) has found that empathy is associated with greater activation in brain mechanisms supporting mentalizing (temporoparietal junction), salience (anterior cingulate cortex; insula), and self-reference (medial prefrontal cortex; precuneus). However, BOLD fMRI has some limitations that may not reliably capture the tonic experience of empathy. To address this, the present study used a perfusion-based arterial spin labeling fMRI approach that provides direct a quantifiable measurement of cerebral blood flow (1 mL/100 g tissue/min) and is less susceptible to low-frequency fluctuations and empathy-based “carry-over” effects that may be introduced by BOLD fMRI–based block designs. Twenty-nine healthy females (mean age = 29 years) were administered noxious heat (48°C; left forearm) during arterial spin labeling fMRI. In the next 2 fMRI scans, female volunteers viewed a stranger (laboratory technician) and their romantic partner, respectively, receive pain-evoking heat (48°C; left forearm) in real-time and positioned proximal to the scanner during fMRI acquisition. Visual analog scale (0 = “not unpleasant”; 10 = “most unpleasant sensation imaginable”) empathy ratings were collected after each condition. There was significantly (P = 0.01) higher empathy while viewing a romantic partner in pain and greater cerebral blood flow in the right temporoparietal junction, amygdala, anterior insula, orbitofrontal cortex, and precuneus when compared with the stranger. Higher empathy was associated with greater precuneus and primary visual cortical activation. The present findings indicate that brain mechanisms supporting the embodiment of another's experience is associated with higher empathy.

Sex Disparities in Mortality After Endovascular Therapy in Large Core Infarcts

Background In recent large core endovascular therapy (EVT) trials of large vessel occlusion acute ischemic stroke (AIS), treatment was associated with reduced rates of mortality. Because post‐AIS mortality can be influenced by societal and biological factors that differ between women and men, we investigate sex‐based differences in mortality outcomes following EVT in large core AIS. Methods From our prospectively collected multicenter registry across 4 comprehensive stroke centers in the Greater Houston area, we identified patients from 2017 to 2022 with large vessel occlusion AIS and large infarct core. Large infarct core was defined by computed tomography perfusion exceeding 70 mL (by regional cerebral blood flow measurements using automated postprocessing) or computed tomography Alberta Stroke Program Early CT [Computed Tomography] Score<6. The primary outcome of this study was the likelihood of mortality at 90 days, determined through multivariable logistic regression adjusted for EVT, sex, and EVT/sex interaction term. Secondary outcomes included 90‐day disability outcomes and intracerebral hemorrhage. Results Among 190 patients who met inclusion criteria, 50% were female and 45.3% received EVT. Demographic differences between the sexes were largely balanced apart from the older age of presentation for women compared with men (75 versus 67, women versus men; P <0.01). In univariable analysis, women who did not receive EVT had greater mortality (27.4% difference; P <0.001) compared with men, with comparable rates in EVT‐treated cohorts. In multivariable analysis, non‐EVT management was strongly associated with mortality in women compared with men at discharge (odds ratio [OR] 5.81, 95% CI [1.96–17.23]) and 90‐days (OR 6.77, 95% CI [2.09–21.94]). In the secondary analysis, which additionally adjusted the model for age and National Institutes of Health Stroke Scale score, these findings were unchanged. The sex/EVT interaction term showed significant interaction for mortality both at discharge and 90 days ( P <0.01). Conclusion EVT in large core AIS populations may disparately reduce mortality in women compared to men.

Noninvasive Monitoring of Changes in Cerebral Hemodynamics During Prolonged Field Care for Hemorrhagic Shock and Hypoxia-Induced Injuries With Portable Diffuse Optical Sensors.

Achieving simultaneous cerebral blood flow (CBF) and oxygenation measures, specifically for point-of-care injury monitoring in prolonged field care, requires the implementation of appropriate methodologies and advanced medical device design, development, and evaluation. The near-infrared spectroscopy (NIRS) method measures the absorbance of light whose attenuation is related to cerebral blood volume and oxygenation. By contrast, diffuse correlation spectroscopy (DCS) allows continuous noninvasive monitoring of microvascular blood flow by directly measuring the degree of light scattering because of red blood cell (RBC) movement in tissue capillaries. Hence, this study utilizes these two optical approaches (DCS-NIRS) to obtain a more complete hemodynamic monitoring by providing cerebral microvascular blood flow, hemoglobin oxygenation and deoxygenation in hemorrhage, and hypoxia-induced injuries. Piglet models of hemorrhage and hypoxia-induced brain injury were used with DCS and NIRS sensors placed over the preorbital to temporal skull regions. To induce hemorrhagic shock, up to 70% of the animal's total blood volume was withdrawn through graded hemorrhage serially via a syringe from a femoral artery cannula in 10 mL/kg aliquots over 1 minute every 10 minutes. A second group of animals was subjected to hypoxia for ∼1 hour through graded hypoxia by serial titration from normoxic fraction inspired oxygen of 21% to hypoxic fraction inspired oxygen of 6%. A subset of animals served as sham-controls undergoing anesthesia, instrumentation, and ventilation as the injury groups, yet experiencing no blood loss or hypoxia. We first investigated the relationship between hemorrhagic shock and no shock by using measured biomarkers, including blood flow index from DCS associated with CBF and oxygenated (HbO) and de-oxygenated hemoglobin from NIRS. The statistical analysis revealed a significant difference between no shock and hemorrhagic shock (P < .01). The HbO decreased with each blood loss as expected, yet the de-oxygenated hemoglobin was slightly changed. During hypoxia-induced global hypoxic-ischemic injury tests, the CBF results from graded hypoxia were consistent with the response previously measured during hemorrhagic shock. Moreover, HbO decreased when the animal was hypoxic, as expected. A statistical analysis was also conducted to compare the results with those of the sham controls. There is a consistency in blood flow measures in both injury mechanisms (hemorrhagic shock and hypoxia), which is significant as the new prototype system provides similar measures and trends for each brain injury type, suggesting that the optical system can be used in response to different injury mechanisms. Notably, the results support the idea that this optical system can probe the hemodynamic status of local cerebral cortical tissue and provide insight into the underlying changes of cerebral tissue perfusion at the microvascular level. These measurement capabilities can improve shock identification and monitoring of medical management of injuries, particularly hemorrhagic shock, in prolonged field care.

A generalized signal model for dual-module velocity-selective arterial spin labeling.

To develop a generalized signal model for dual-module velocity-selective arterial spin labeling (dm-VSASL) that can integrate arbitrary saturation and inversion profiles. A recently developed mathematical framework for single-module VSASL is extended to address the increased complexity of dm-VSASL and to model the use of realistic velocity-selective profiles in the label-control and vascular crushing modules. Expressions for magnetization difference, arterial delivery functions, labeling efficiency, and cerebral blood flow (CBF) estimation error are presented. Sources of error are examined and timing requirements to minimize quantification errors are derived. For ideal velocity-selective profiles, the predicted signals match those of prior work. With realistic profiles, a CBF-dependent estimation error can occur when velocity-selective inversion (VSI) is used for the labeling modules and velocity-selective saturation (VSS) is used for the vascular crushing module. The error reflects a mismatch between the leading and trailing edges of the delivery function for the second bolus and can be minimized by choosing a nominal labeling cutoff velocity that is lower than the nominal saturation cutoff velocity. In the presence of and inhomogeneities, the labeling efficiency of dual-module VSI is more attenuated than that of dual-module VSS. The proposed signal model will enable researchers to more accurately assess and compare the performance of realistic dm-VSASL implementations and improve the quantification of dm-VSASL CBF measures.

Shifting concepts of autoregulation: Commentary to 'static autoregulation in humans'.

Advances in imaging techniques have transformed our understanding of cerebral autoregulation. Older imaging techniques provided measurements of cerebral blood flow (CBF) that reflected the average CBF over a window of 10-20 minutes. A key finding, dating back to 1959, was that CBF remained more or less stable over a remarkably wide range of changes in blood pressure. Modern techniques can measure changes in CBF within the time frame of a heartbeat. They have revealed, paradoxically, a remarkable instability of CBF. This commentary attempts to reconcile these seemingly contradictory observations.

Simultaneous and cumulative effects of tDCS on cerebral metabolic rate of oxygen in multiple sclerosis.

Transcranial direct current stimulation (tDCS) is a non-invasive neuromodulation technique with simultaneous (during stimulation) and cumulative effects (after repeated sessions) on blood flow and neuronal metabolism. These effects remain mostly unclear especially in multiple sclerosis (MS). This work aims to elucidate brain metabolic and hemodynamic underpinnings of tDCS and its potential therapeutic impact in MS patients using quantitative tDCS-MRI. MS participants (n = 20; age = 45.4 ± 12.3 years, 7 males) underwent 3 T MRI scans before and after 20 daily sessions of dorsolateral prefrontal cortex (DLFPC) tDCS (2.0 mA, left anodal) paired with adaptive cognitive training (aCT). During both visits, imaging measurements of cerebral blood flow (CBF), cerebral venous blood oxygenation (Yv) and calculated cerebral metabolic rate of oxygen (CMRO2) were obtained at pre-tDCS, during-tDCS and post-tDCS. At baseline, significant increase from pre- to during-tDCS was observed in CMRO2 (7.6%; p = 0.002), CBF (11.0%; p < 0.0001) and Yv (1.9%; p = 0.006). At follow up, we observed an increase in pre-tDCS CMRO2 (140.59 ± 13.83 μmol/100 g/min) compared to baseline pre-tDCS levels (128.30 ± 14.00 μmol/100 g/min; p = 0.006). Sustained elevations in CMRO2 and CBF into post-tDCS were also observed (tDCS lingering effects). Cumulative tDCS effects were observed in the form of sustained elevations in CMRO2 and CBF in pre-tDCS follow up, reaching the magnitudes measured at baseline during-tDCS. TDCS induces an acute surge in metabolic activity persisting immediately after the stimulation is removed. Moreover, treatment composed of repeated tDCS-aCT paired sessions contributes to establishing long-lasting increases in neuronal activity.

Arterial Spin Labeling Magnetic Resonance Imaging for Acute Disorders of Consciousness in the Intensive Care Unit.

To investigate patients with disorders of consciousness (DoC) for residual awareness, guidelines recommend quantifying glucose brain metabolism using positron emission tomography. However, this is not feasible in the intensive care unit (ICU). Cerebral blood flow (CBF) assessed by arterial spin labeling magnetic resonance imaging (ASL-MRI) could serve as a proxy for brain metabolism and reflect consciousness levels in acute DoC. We hypothesized that ASL-MRI would show compromised CBF in coma and unresponsive wakefulness states (UWS) but relatively preserved CBF in minimally conscious states (MCS) or better. We consecutively enrolled ICU patients with acute DoC and categorized them as being clinically unresponsive (i.e., coma or UWS [≤ UWS]) or low responsive (i.e., MCS or better [≥ MCS]). ASL-MRI was then acquired on 1.5T or 3T. Healthy controls were investigated with both 1.5T and 3T ASL-MRI. We obtained 84 ASL-MRI scans from 59 participants, comprising 36 scans from 35 patients (11 women [31.4%]; median age 56years, range 18-82years; 24 ≤ UWS patients, 12 ≥ MCS patients; 32 nontraumatic brain injuries) and 48 scans from 24 healthy controls (12 women [50%]; median age 50years, range 21-77years). In linear mixed-effects models of whole-brain cortical CBF, patients had 16.2mL/100g/min lower CBF than healthy controls (p = 0.0041). However, ASL-MRI was unable to discriminate between ≤ UWS and ≥ MCS patients (whole-brain cortical CBF: p = 0.33; best hemisphere cortical CBF: p = 0.41). Numerical differences of regional CBF in the thalamus, amygdala, and brainstem in the two patient groups were statistically nonsignificant. CBF measurement in ICU patients using ASL-MRI is feasible but cannot distinguish between the lower and the upper ends of the acute DoC spectrum. We suggest that pilot testing of diagnostic interventions at the extremes of this spectrum is a time-efficient approach in the continued quest to develop DoC neuroimaging markers in the ICU.

Differentiation Between High-Grade Glioma and Brain Metastasis Using Cerebral Perfusion-Related Parameters (Cerebral Blood Volume and Cerebral Blood Flow): A Systematic Review and Meta-Analysis of Perfusion-weighted MRI Techniques.

Distinguishing high-grade gliomas (HGGs) from brain metastases (BMs) using perfusion-weighted imaging (PWI) remains challenging. PWI offers quantitative measurements of cerebral blood flow (CBF) and cerebral blood volume (CBV), but optimal PWI parameters for differentiation are unclear. To compare CBF and CBV derived from PWIs in HGGs and BMs, and to identify the most effective PWI parameters and techniques for differentiation. Systematic review and meta-analysis. Twenty-four studies compared CBF and CBV between HGGs (n = 704) and BMs (n = 488). Arterial spin labeling (ASL), dynamic susceptibility contrast (DSC), dynamic contrast-enhanced (DCE), and dynamic susceptibility contrast-enhanced (DSCE) sequences at 1.5 T and 3.0 T. Following the PRISMA guidelines, four major databases were searched from 2000 to 2024 for studies evaluating CBF or CBV using PWI in HGGs and BMs. Standardized mean difference (SMD) with 95% CIs was used. Risk of bias (ROB) and publication bias were assessed, and I2 statistic was used to assess statistical heterogeneity. A P-value<0.05 was considered significant. HGGs showed a significant modest increase in CBF (SMD = 0.37, 95% CI: 0.05-0.69) and CBV (SMD = 0.26, 95% CI: 0.01-0.51) compared with BMs. Subgroup analysis based on region, sequence, ROB, and field strength for CBF (HGGs: 375 and BMs: 222) and CBV (HGGs: 493 and BMs: 378) values were conducted. ASL showed a considerable moderate increase (50% overlapping CI) in CBF for HGGs compared with BMs. However, no significant difference was found between ASL and DSC (P = 0.08). ASL-derived CBF may be more useful than DSC-derived CBF in differentiating HGGs from BMs. This suggests that ASL may be used as an alternative to DSC when contrast medium is contraindicated or when intravenous injection is not feasible. Stage 2.

Identification of toll-like receptor 2 as a key regulator of neuronal apoptosis in vascular dementia by bioinformatics analysis and experimental validation

BackgroundVascular dementia (VaD), the second most prevalent type of dementia, lacks a well-defined cause and effective treatment. Our objective was to utilize bioinformatics analysis to discover the fundamental disease-causing genes and pathological mechanisms in individuals diagnosed with VaD. MethodsTo identify potential pathogenic genes associated with VaD, we conducted weighted gene co-expression network analysis (WGCNA), differential expression analysis, and protein–protein interaction (PPI) analysis. The exploration of potential biological mechanisms involved the utilization of Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis. Moreover, a bilateral common carotid artery stenosis (BCAS) mouse model of VaD was established, and the expression of the hub gene, its relationship with cognitive function and its potential pathogenic mechanism were verified by cognitive behavior tests, cerebral blood flow measurement, Western blotting, and immunofluorescence experiments. ResultsThis study identified 293 DEGs from the brain cortex of VaD patients and healthy controls, among these genes, the Toll-like receptor 2 (TLR2) gene was identified as hub gene, and it was associated with the apoptosis-related pathway PI3K/AKT.The BCAS model demonstrated that the use of TLR2 inhibitors greatly enhanced the cognitive function of the mice (p < 0.05). Additionally, there was a notable decrease in the number of apoptotic cells in the brain cortex of the mice (p < 0.01). Moreover, significant alterations in the levels of proteins related to the PI3K/AKT pathway and cleaved-caspase3 proteins were detected (p < 0.05). ConclusionsTLR2 plays a role in the pathophysiology of VaD by enhancing the neuronal apoptotic pathway, suggesting it could be a promising therapeutic target.

Multi-Tracer Studies of Brain Oxygen and Glucose Metabolism Using a Time-of-Flight Positron Emission Tomography - Computed Tomography Scanner.

The authors have developed a paradigm using positron emission tomography (PET) with multiple radiopharmaceutical tracers that combines measurements of cerebral metabolic rate of glucose (CMRGlc), cerebral metabolic rate of oxygen (CMRO2), cerebral blood flow (CBF), and cerebral blood volume (CBV), culminating in estimates of brain aerobic glycolysis (AG). These in vivo estimates of oxidative and non-oxidative glucose metabolism are pertinent to the study of the human brain in health and disease. The latest positron emission tomography-computed tomography (PET-CT) scanners provide time-of-flight (TOF) imaging and critical improvements in spatial resolution and reduction of artifacts. This has led to significantly improved imaging with lower radiotracer doses. Optimized methods for the latest PET-CT scanners involve administering a sequence of inhaled 15O-labeled carbon monoxide (CO) and oxygen (O2), intravenous 15O-labeled water (H2O), and 18F-deoxyglucose (FDG)-all within 2-h or 3-h scan sessions that yield high-resolution, quantitative measurements of CMRGlc, CMRO2, CBF, CBV, and AG. This methods paper describes practical aspects of scanning designed for quantifying brain metabolism with tracer kinetic models and arterial blood samples and provides examples of imaging measurements of human brain metabolism.

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

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. 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. 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 80Hz. 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. Given its cost-effectiveness, scalability, and simplicity, this laser-centric tool offers significant potential in advancing noninvasive cerebral monitoring technologies.

Simultaneous assessment of blood flow and myelin content in the brain white matter with dynamic [11C]PiB PET: a test-retest study in healthy controls.

Exploring the relationship between oxygen supply and myelin damage would benefit from a simultaneous quantification of myelin and cerebral blood flow (CBF) in the brain's white matter (WM). To validate an analytical method for quantifying both CBF and myelin content in the WM using dynamic [11C]PiB positron emission tomography (PET). A test-retest study was performed on eight healthy subjects who underwent two consecutive dynamic [11C]PiB-PET scans. Three quantitative approaches were compared: simplified reference tissue model 2 (SRTM2), LOGAN graphical model, and standardized uptake value ratio (SUVR). The sensitivity of methods to the size of the region of interest was explored by simulating lesion masks obtained from 36 subjects with multiple sclerosis. Reproducibility was assessed using the relative difference and interclass correlation coefficient. Repeated measures correlations were used to test for cross-correlations between metrics. Among the CBF measures, the relative delivery (R1) of the simplified reference tissue model 2 (SRTM2) displayed the best reproducibility in the white matter, with a strong influence of the size of regions analyzed, the test-retest variability being below 10% for regions above 68 mm3 in the supratentorial white matter. [11C]PiB PET-derived proxies of CBF demonstrated lower perfusion of white matter compared to grey matter with an overall ratio equal to 1.71 ± 0.09 when the SRTM2-R1 was employed. Tissue binding in the white matter was well estimated by the Logan graphical model through estimation of the distribution volume ratio (LOGAN-DVR) and SRTM2 distribution volume ratio (SRTM2-DVR), with test-retest variability being below 10% for regions exceeding 106 mm3 for LOGAN-DVR and 300 mm3 for SRTM2-DVR. SRTM2-DVR provided a better contrast between white matter and grey matter. The interhemispheric variability was also dependent on the size of the region analyzed, being below 10% for regions above 103 mm3 for SRTM2-R1 and above 110 mm3 for LOGAN-DVR. Whereas the 1 to 8-minute standardized uptake value ratio (SUVR1-8) showed an intermediary reproducibility for CBF assessment, SUVR0-2 for perfusion or SUVR50-70 for tissue binding showed poor reproducibility and correlated only mildly with SRTM2-R1 and LOGAN-DVR estimations respectively. [11C]PiB PET imaging can simultaneously quantify perfusion and myelin content in WM diseases associated with focal lesions. For longitudinal studies, SRTM2-R1 and DVR should be preferred over SUVR for the assessment of regional CBF and myelin content, respectively. European Union Clinical Trials Register EUDRACT; EudraCT Number: 2008-004174-40; Date: 2009-03-06; https//www.clinicaltrialsregister.eu ; number 2008-004174-40.

Choosing a camera and optimizing system parameters for speckle contrast optical spectroscopy

Speckle contrast optical spectroscopy (SCOS) is an emerging camera-based technique that can measure human cerebral blood flow (CBF) with high signal-to-noise ratio (SNR). At low photon flux levels typically encountered in human CBF measurements, camera noise and nonidealities could significantly impact SCOS measurement SNR and accuracy. Thus, a guide for characterizing, selecting, and optimizing a camera for SCOS measurements is crucial for the development of next-generation optical devices for monitoring human CBF and brain function. Here, we provide such a guide and illustrate it by evaluating three commercially available complementary metal–oxide–semiconductor cameras, considering a variety of factors including linearity, read noise, and quantization distortion. We show that some cameras that are well-suited for general intensity imaging could be challenged in accurately quantifying spatial contrast for SCOS. We then determine the optimal operating parameters for the preferred camera among the three and demonstrate measurement of human CBF with this selected low-cost camera. This work establishes a guideline for characterizing and selecting cameras as well as for determining optimal parameters for SCOS systems.

Test-retest reliability of resting-state cerebral blood flow quantification using pulsed Arterial Spin Labeling (PASL) over 3 weeks vs 8 weeks in healthy controls

Arterial Spin Labeling is a valuable functional imaging tool for both clinical and research purposes. However, little is known about the test-retest reliability of cerebral blood flow measurements over longer periods. In this study, we investigated the reliability of pulsed Arterial Spin Labeling in assessing cerebral blood flow over a 3 (n = 28) vs 8 (n = 19) weeks interscan interval in 47 healthy participants. As a measure of cerebral blood flow reliability, we calculated voxel-wise, whole-brain, and regions of interest intraclass correlation coefficients. The whole-brain mean resting-state cerebral blood flow showed good to excellent reliability over time for both periods (intraclass correlation coefficients = 0.85 for the 3-week delay, intraclass correlation coefficients = 0.53 for the 8-week delay). However, the voxel-wise and regions of interest intraclass correlation coefficients fluctuated at 8-week compared to the 3-week interval, especially within cortical areas. These results confirmed previous findings that Arterial Spin Labeling could be used as a reliable method to assess brain perfusion. However, as the reliability seemed to decrease over time, caution is warranted when performing correlations with other variables, especially in clinical populations.

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.

Comparing two MRI methods to assess fundamental sex differences in resting cerebral blood flow

Background: Cerebral blood flow (CBF) is a critical measurement for understanding healthy brain physiology prior to aging or neurologic diseases. Patterns of stroke and neurologic pathologies are often sex-specific. Therefore, it is important to understand basic sex differences in CBF, which are often associated with poor brain outcomes. Furthermore, prior literature examining sex differences in CBF is confounded by age, comorbidities, medications, lack of control of menstrual cycle and/or hormonal contraceptive use, and methodological discrepancies. The objective of this study was to compare two different magnetic resonance imaging (MRI) methods of quantifying CBF in young adults while controlling for the aforementioned confounding factors. We hypothesized that females would display higher CBF than males, and that there would be a high reliability between Arterial Spin Labeling (ASL) and 4D Flow MRI. Methods: 30 males and 26 females (23 ± 4yr) were studied on a single MRI (3T) visit. Subjects were fasted 8 hours and withheld caffeine, exercise, and NSAIDs for at least 24 hours. Females were not taking hormonal contraception and were studied on days 1-7 of the menstrual cycle. Microvascular CBF (mL/100g/min) was assessed via pseudo-continuous ASL (pcASL) while 4D Flow MRI acquired with Phase Contrast Vastly undersampled Isotropic Projection Reconstruction (PC VIPR) yielded macrovascular flow via the larger cerebral arteries, summing the internal carotid arteries and basilar artery for total CBF (mL/min). A T1-weighted MRI scan was used to provide brain volumes, allowing CBF from PC VIPR to be normalized and compared to ASL (mL/100g/min). The scans were taken consecutively, with subjects breathing normoxic gas while hemodynamics and end tidal CO2 were monitored. Regression analysis was used to determine reliability of two measures to test a sex difference in CBF. Results: Linear regression analysis demonstrated reliability between measurements of resting CBF via ASL and PC VIPR (p&lt;0.001, R2=0.621). However, ASL measured significantly higher blood flows than PC VIPR in females (63.40 ± 8.55 vs. 56.47 ± 8.48 mL/100g/min, p&lt;0.001) while male subjects had similar flows measured by both methods (45.75 ± 9.39 vs. 46.69 ± 8.19 mL/100g/min, p=0.464). Females displayed an increase in resting CBF compared to males, being 27.8% and 17.3% higher in the ASL and PC VIPR flow measurements (both p&lt;0.001), respectively. Conclusions: These results demonstrate that ASL and PC VIPR CBF display a strong correlation, and that females have greater resting CBF compared to males that is detected by both MRI methods of quantification. However, ASL resulted in greater flow measurements in females, resulting in larger differences being observed (27.8% versus 17.3%). This discrepancy in CBF quantification warrants further investigation to determine the optimal mode of CBF measurement and comparison. Funding by NIH (HL150361). 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.

Day-to-day repeatability of total and regional cerebral blood flow

Background: Measuring cerebral blood flow (CBF) has been crucial in understanding brain function and health. Most studies use a resting CBF value for comparison when testing different experimental conditions on different days; however, it is unclear whether resting condition values can be repeated between days. This has important implications for intervention or mechanistic studies. We hypothesize that resting CBF will be repeatable across different days in a well-controlled setting using MRI based pseudo-continuous arterial spin labeling (pcASL). Methods: Seven subjects (1F, 6M) were studied on two separate occasions after abstaining from caffeine, NSAIDs and exercise for 24 hours, and fasting for 8 hours. The end tidal CO2 had to be within 2mmHg between visits. Female subjects were on days 1-7 of their menstrual cycle and were not taking any hormonal contraception. CBF was quantified via MRI based pseudo-continuous Arterial Spin Labeling (pcASL) during both visits and expressed relative to gray and white matter (mL/min/100g). Data focuses on total grey matter, total white matter, and 8 emotional and memory regions. The repeatability of all CBF values was tested between both MRI visits using linear regression. Results: Scans were completed 113± 81 days apart. R2 values showed a weak effect size for grey matter (R2 =0.454) and a moderate effect size for white matter (R2 =0.527). When measuring for the 8 regions of the brain, there were no significant p-values, and weak R2 effect size for the accumbens (p=0.107, R2 =0.454), amygdala (p=0.204, R2 =0.299), anterior cingulate (p=0.092, R2 =0.463), caudate (p=0.122, R2 =0.409) hippocampus (p=0.175, R2 =0.332), and parahippocampus (p=0.183, R2 =0.323). In brain regions involved with memory, the entorhinal cortex indicated a R2 value of moderate effect size (p=0.068, R2 =0.519) t (p=0.068), as well as the precuneus (p=0.060, R2 =0.54) Conclusion: The results suggest that resting CBF demonstrates low repeatability between days. Noteworthy trends exist in the entorhinal cortex and precuneus, which both are involved in memory. These findings suggest that when comparing resting CBF, researchers may want to consider collecting new resting CBF measurements every time they are testing for reactivity since there might be variability in areas such as the accumbens, amygdala, anterior cingulate, caudate, hippocampus and parahippocampus. Funding: NIH R01 HL150361. 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.

Metabolic Diaschisis in Mild Traumatic Brain Injury.

Neurophysiological diaschisis presents in traumatic brain injury (TBI) as functional impairment distant to the lesion site caused by axonal neuroexcitation and deafferentation. Diaschisis studies in TBI models have evaluated acute phase functional and microstructural changes. Here, in vivo biochemical changes and cerebral blood flow (CBF) dynamics following TBI are studied with magnetic resonance. Behavioral assessments, magnetic resonance spectroscopy (MRS), and CBF measurements on rats followed cortical impact TBI. Data were acquired pre-TBI and 1-3 h, 2-days, 7-days, and 14-days post-TBI. MRS was performed on the ipsilateral and contralateral sides in the cortex, striatum, and thalamus. Metabolites measured by MRS included N-acetyl aspartate (NAA), aspartate (Asp), lactate (Lac), glutathione (GSH), and glutamate (Glu). Lesion volume expanded for 2 days post-TBI and then decreased. Ipsilateral CBF dropped acutely versus baseline on both sides (-62% ipsilateral, -48% contralateral, p < 0.05) but then recovered in cortex, with similar changes in ipsilateral striatum. Metabolic changes versus baseline included increased Asp (+640% by Day 7 post-TBI, p < 0.05) and Lac (+140% on Day 2 post-TBI, p < 0.05) in ipsilateral cortex, while GSH (-67% acutely, p < 0.05) and NAA decreased (-50% on Day 2, p < 0.05). In contralateral cortex Lac decreased (-73% acutely, p < 0.05). Analysis of variance showed significance for Side (p < 0.05), Time after TBI (p < 0.05), and interactions (p < 0.005) for Asp, GSH, Lac, and NAA. Transient decreases of GSH (-30%, p < 0.05, acutely) and NAA (-23% on Day 2, p < 0.05) occurred in ipsilateral striatum with reduced GSH (-42%, p < 0.005, acutely) in the contralateral striatum. GSH was decreased in ipsilateral thalamus (-59% ipsilateral on Day 2, p < 0.05). Delayed increases of total choline were seen in the contralateral thalamus were noted as well (+21% on Day 7 post-TBI, p < 0.05). Both CBF and neurometabolite concentration changes occurred remotely from the TBI site, both ipsilaterally and contralaterally. Decreased Lac levels on the contralateral cortex following TBI may be indicative of reduced anaerobic metabolism during the acute phase. The timing and locations of the changes suggest excitatory and inhibitory signaling processes are affecting post-TBI metabolic fluctuations.

Non-invasive, Continuous Measurement of Cerebral Blood Flow During Progression to Brain Death (P1-2.002)

Non-invasive, Continuous Measurement of Cerebral Blood Flow During Progression to Brain Death (P1-2.002)

Dynamic Light Scattering in Biomedical Applications: feature issue introduction

The feature Issue on “Dynamic Light Scattering in Biomedical Applications” presents a compilation of research breakthroughs and technological advancements that have shaped the field of biophotonics, particularly in the non-invasive exploration of biological tissues. Highlighting the significance of dynamic light scattering (DLS) alongside techniques like laser Doppler flowmetry (LDF), diffusing wave spectroscopy (DWS), and laser speckle contrast imaging (LSCI), this issue underscores the versatile applications of these methods in capturing the intricate dynamics of microcirculatory blood flow across various tissues. Contributions explore developments in fluorescence tomography, the integration of machine learning for data processing, enhancements in microscopy for cancer detection, and novel approaches in optical biophysics, among others. Innovations featured include a high-resolution speckle contrast tomography system for deep blood flow imaging, a rapid estimation technique for real-time tissue perfusion imaging, and the use of convolutional neural networks for efficient blood flow mapping. Additionally, studies delve into the impact of skin strain on spectral reflectance, the sensitivity of cerebral blood flow measurement techniques, and the potential of photobiomodulation for enhancing brain function. This issue not only showcases the latest theoretical and experimental strides in DLS-based imaging but also anticipates the continued evolution of these modalities for groundbreaking applications in disease detection, diagnosis, and monitoring, marking a pivotal contribution to the field of biomedical optics.