Cerebral Blood Flow Research Articles

Transcranial Direct Current Stimulation to Provide Neuroprotection and Enhance Cerebral Blood Flow in Stroke: A Comprehensive Review

Stroke remains a leading cause of global disability and mortality despite advancements in acute interventions. Transcranial direct current stimulation (tDCS), a non-invasive neuromodulation technique, has primarily been studied for its effects on cortical excitability, with limited exploration of its neuroprotective and hemodynamic benefits. This review examines the role of tDCS in stroke, with a focus on neuroprotection in acute settings and cerebral blood flow (CBF) modulation in both acute and chronic phases. tDCS offers rapid, localized delivery to salvageable ischemic tissue, exerting pleiotropic effects that address a broader spectrum of pathological processes compared to pharmacological agents. Cathodal tDCS shows promise in acute ischemic stroke for neuroprotection in small-scale clinical studies, enhancing CBF and promoting vessel recanalization, while anodal tDCS demonstrates stronger effects on CBF, particularly in chronic stroke and hypoperfusion cases. Bihemispheric stimulation may offer additional benefits, with evidence suggesting a dose-dependent relationship between stimulation parameters and therapeutic outcomes. Further research is warranted to optimize stimulation protocols, evaluate safety and feasibility, and explore the potential of tDCS to promote neuroplasticity and functional recovery across different stroke populations and stages. By addressing these gaps, tDCS could emerge as a valuable adjunctive therapy in stroke management, complementing current interventions and expanding therapeutic windows.

Cerebral blood flow following successful living kidney transplantation: VINTAGE study

Abstract Background Chronic kidney disease (CKD) is a significant risk factor for cerebrovascular disease. However, there is limited research on how successful living donor kidney transplantation (LDKT) affects cerebral blood flow (CBF). This study aims to comprehensively investigate how LDKT influences CBF across various brain levels and regions. Methods Data from 53 recipients between 2016 and 2020 were obtained from the VINTAGE study conducted at our hospital. CBF was measured by level and region using single-photon emission computed tomography (SPECT), according to the Talairach brain atlas. The primary endpoint was the mean difference in CBF before and 1-year post-LDKT. Subgroup analysis using traditional risk factors assessed the heterogeneity of the effect on CBF in the frontal lobe region. Results LDKT improved blood flow in the anterior cerebral artery and middle cerebral artery but had less impact on the posterior cerebral artery. The most consistent improvements were observed in the frontal lobe region (left frontal lobe: -0.12 [95% CI -0.18 to -0.05, P < 0.001]; right frontal lobe: -0.13 [95% CI -0.21 to -0.05, P = 0.001]. Subgroup analysis showed a consistent effect of LDKT on frontal lobe CBF improvement, with no qualitative interaction observed. Conclusions LDKT contributes to the normalization of CBF, with improvement in anterior circulation and frontal lobe blood flow. To clarify the clinical significance of KT's CBF-improving effect, future studies should investigate the relationship between specific cognitive impairments (e.g. short-term memory, visuospatial ability, executive function) and CBF in each perfusion region.

Cerebral Oxygen Metabolic Stress in Children and Adults With Large Vessel Vasculopathy Due to Sickle Cell Disease.

Large vessel vasculopathy (LVV), or moyamoya syndrome, increases the risk of stroke in patients with sickle cell disease (SCD), yet effective treatments are lacking. In atherosclerotic carotid disease, previous studies demonstrated elevated oxygen extraction fraction (OEF) as a predictor of ipsilateral stroke. In a SCD cohort, we examined hemispheric hemodynamic and oxygen metabolic dysfunction as tissue-based biomarkers of cerebral ischemic risk in patients with LVV. Children and adults with SCD were recruited from a SCD clinic associated with a tertiary medical center and underwent prospective brain MRI and MR angiography. LVV was defined as ≥75% stenosis in a major anterior circulation artery, excluding occlusion or previous revascularization surgery. Baseline characteristics, cerebral blood flow (CBF), normalized OEF (nOEF), infarct volume, white matter microstructure, and brain volume were compared in hemispheres with vs without LVV. In a cross-sectional analysis, mixed-effects linear multivariable models examined the effect of LVV on: (1) CBF and nOEF, as tissue markers of hemodynamic and oxygen metabolic stress, respectively, and (2) endpoints of cerebral ischemic injury including infarct volume, white matter microstructure, and brain volume. Of 155 patients (22 [12-31] years, 57% female), 33 (21%) had ≥25% stenosis, 22 (14%) had ≥50% stenosis, 14 (9%) had 75%-99% stenosis, and 5 (3%) had 100% occlusion. After excluding hemispheres with previous revascularization surgery, LVV was present in 16 hemispheres from 11 patients. Hemispheres with (N = 16) vs without (N = 283) LVV had lower CBF (25.2 vs 32.1 mL/100 g/min, p = 0.01) and higher nOEF (0.99 vs 0.95, p = 0.02). On multivariable analysis, CBF was nonsignificantly lower (β = -0.16, p = 0.07) while nOEF remained higher in hemispheres with LVV (β = 0.04, p = 0.03). Moreover, LVV was associated with greater hemispheric infarct volume, microstructural disruption, and atrophy. Beyond greater infarct burden, LVV was associated with hemispheric atrophy and white matter microstructural injury. As an indicator of active hypoxia, elevated nOEF likely represents a compensatory response to flow-limiting stenosis in hemispheres with LVV. The study is limited by a small number of patients with severe stenosis. Future studies are needed to evaluate the potential of tissue-based CBF and nOEF in assessing stroke risk and guide timely treatment of vasculopathy in SCD.

Passive and active exercise do not mitigate mental fatigue during a sustained vigilance task.

Executive function (EF) is improved following a single bout of exercise and impaired when an individual experiences mental fatigue (MF). These performance outcomes have been linked to a bi-directional change in cerebral blood flow (CBF). Here, we sought to determine whether MF-induced by a sustained vigilance task (i.e., psychomotor vigilance task: PVT) is mitigated when preceded by a single bout of exercise. Participants completed 20-min single bouts of active exercise (cycle ergometry involving volitional muscle activation), passive exercise (cycle ergometry involving a mechanical flywheel) and a non-exercise control intervention. EF was assessed pre- and post-intervention via the antisaccade task. Following each intervention, a 20-min PVT was completed to induce and assess MF, and transcranial Doppler ultrasound of middle cerebral artery velocity (MCAv) was used to estimate intervention- and PVT-based changes in CBF. Active and passive exercise provided a post-intervention reduction in antisaccade reaction times; that is, exercise benefitted EF. Notably, however, frequentist and Bayesian statistics indicated the EF benefit did not mitigate MF during the PVT. As well, although exercise (active and passive) and the PVT respectively increased and decreased CBF, these changes were not correlated with behavioral measures of EF or MF. Accordingly, a postexercise EF benefit does not mitigate MF during a sustained vigilance task and a bi-directional change in CBF does not serve as a primary mechanism associated with EF and MF changes. Such results provide a framework for future work to explore how different exercise types, intensities and durations may impact MF.

Relationship between the amplitudes of cerebral blood flow velocity and intracranial pressure using linear and non-linear approach.

Intracranial pressure (ICP), cerebral blood flow and volume are affected by craniospinal elasticity and cerebrospinal fluid dynamics, interacting in complex, nonlinear ways. Traumatic brain injury (TBI) may significantly alter this relationship. This retrospective study investigated the relationship between the vascular and parenchymal intracranial compartments by analysing two amplitudes: cerebral blood flow velocity (AmpCBFV) and ICP (AMP) during hypocapnia manoeuvre in TBI patients. Twenty-nine TBI patients hospitalised at Addenbrooke's Hospital, whose ICP and CBFV were monitored during mild hypocapnia, were included. A linear metric of the relationship was defined as a moving-window correlation (R) between AmpCBFV and AMP, named RAMP. Nonlinear metrics were based on the Joint Symbolical Analysis (JSA) algorithm, which transforms AmpCBFV and AMP into sequences of symbols ('words') using a binary scheme with word lengths of three. The mean AmpCBFV and AMP were not significantly correlated at baseline (r = -0.10) or during hypocapnia (r = -0.19). However, the RAMP index was significantly higher at baseline (0.64 ± 0.04) compared to hypocapnia (0.57 ± 0.04, p = 0.035). The relative frequency of symmetrical word types (JSAsym) describing the AmpCBFV-AMP interaction decreased during hypocapnia (0.35 ± 0.30) compared to baseline (0.44 ± 0.030; p = 0.004). Our results indicate that while the grouped-averaged AmpCBFV and AMP were not significantly correlated, either at baseline or during hypocapnia, significant changes were observed when using RAMP and JSA indices. Further validation of these new parameters, which reflect the association between the vascular and parenchymal intracranial compartments, is needed in a larger cohort.

Feasibility of utilizing functional near-infrared spectroscopy to measure the cognitive load of paramedicine students undertaking high-acuity clinical simulations in Australia: a case study.

Paramedicine education often uses high-fidelity simulations that mimic real-life emergencies. These experiences can trigger stress responses characterized by physiological changes, including alterations in cerebral blood flow and oxygenation. Functional near-infrared spectroscopy (fNIRS) is emerging as a promising tool for assessing cognitive stress in educational settings. Eight final-year undergraduate paramedicine students completed 2 high-acuity scenarios 7 days apart. Real-time continuous recording of cerebral blood flow and oxygenation levels in the prefrontal cortex was undertaken via fNIRS as a means of assessing neural activity during stressful scenarios. fNIRS accurately determined periods of increased cerebral oxygenation when participants were undertaking highly technical skills or making significant clinical decisions. fNIRS holds potential for objectively measuring the cognitive load in undergraduate paramedicine students. By providing real-time insights into neurophysiological responses, fNIRS may enhance training outcomes in paramedicine programs and improve student well-being (Australian New Zealand Clinical Trials Registry: ACTRN12623001214628).

Recanalization Does Not Always Equate to Reperfusion: No-Reflow Phenomenon After Successful Thrombectomy.

Thrombectomy for acute large vessel occlusion is a well-established treatment for stroke prevention. However, futile recanalization cases, where no-reflow occurs despite successful recanalization, have been reported. This study aimed to assess cerebral hemodynamics immediately after thrombectomy and their relationship with clinical outcomes. We prospectively enrolled patients who underwent successful thrombectomy (modified Thrombolysis in Cerebral Infarction [TICI] ≥2b) for internal carotid artery or middle cerebral artery occlusions at Nagasaki University Hospital between January 2021 and December 2023. Preoperative magnetic resonance imaging was performed, followed by flat-panel computed tomography perfusion 30 minutes after recanalization. Areas with cerebral blood flow <45%, Tmax >6 seconds, and cerebral blood volume <34%, 38%, and 42% were analyzed, and hypoperfusion intensity ratio and cerebral blood volume index were calculated using Rapid ANGIO. We assessed the correlation of these parameters with infarct expansion, hemorrhagic transformation, and poor outcomes, defined as modified Rankin Scale scores of 4 to 6, at 3 months. A total of 65 cases were analyzed. Infarct expansion, defined as a decrease in Alberta Stroke Program Early CT Score, occurred in 23 cases (12/28 TICI 2b and 11/37 TICI 2c/3). No-reflow, defined as Tmax >6 seconds, was observed in 80% of cases (52/65), regardless of TICI grade. The infarct expansion group in TICI 2b had a significantly larger residual cerebral blood flow <45% area (32.9±30.4 versus 10.6±14.5 mL) and a lower cerebral blood volume index (0.71±0.2 versus 0.92±0.2). Cerebral blood flow <45% (r=-0.57; P<0.001) and cerebral blood volume <34% (r=-0.40; P=0.001), not Tmax >6 seconds, negatively correlated with postoperative Alberta Stroke Program Early CT Score. In logistic regression analysis, cerebral blood flow <45% was an independent predictor of poor outcomes (adjusted odds ratio, 1.05 [95% CI, 1.00-1.11]; P=0.039). No-reflow is common after thrombectomy, suggesting that successful recanalization does not always result in immediate tissue reperfusion. Hemodynamic impairment postthrombectomy may persist, highlighting the need for adjunctive treatments.

Longitudinal changes in white matter free water in cerebral small vessel disease: Relationship to cerebral blood flow and white matter fiber alterations.

White matter (WM) free water (FW) is a potential imaging marker for cerebral small vessel disease (CSVD). This study aimed to characterize longitudinal changes in WM FW and investigate factors contributing to its elevation in CSVD. We included 80 CSVD patients and 40 normal controls (NCs) with multi-modality MRI data. Cerebral blood flow (CBF) was measured, and fiber alterations were assessed using total apparent fiber density (AFDt). FW were extracted from whole WM, white matter hyperintensities (WMH) and normal-appearing WM (NAWM). Baseline and longitudinal FW elevation were compared between patients and NCs, and between WMH and NAWM. We investigated whether baseline vascular risk factor score, CBF, and AFDt could predict longitudinal FW elevation. Association between cognition and WM FW in CSVD was also assessed. Results shown that FW was higher and increased faster in CSVD compared to NCs and in WMH compared to NAWM. Baseline AFDt predicted longitudinal FW elevation in CSVD patients, while CBF predicted FW changes only in controls. WM FW was associated with cognitive impairment. These findings suggest that CSVD is associated with a faster increase in WM FW. Hypoperfusion and WM fiber alterations might accelerate FW elevation, which is associated with cognitive decline.

Regional dynamic cerebral autoregulation across anterior and posterior circulatory territories: A detailed exploration and its clinical implications.

Cerebral autoregulation (CA) is the mechanism that maintains stable cerebral blood flow (CBF) despite fluctuations in systemic blood pressure, crucial for brain homeostasis. Recent evidence highlights distinct regional variations in CA between the anterior (carotid) and posterior (vertebrobasilar) circulations. Non-invasive neuromonitoring techniques, such as transcranial Doppler, transfer function analysis, and near-infrared spectroscopy, facilitate the dynamic assessment of CBF and autoregulation. Studies indicate a robust autoregulatory capacity in the anterior circulation, characterized by rapid adjustments in vascular resistance. On the contrary, the posterior circulation, mainly supplied by the vertebral arteries, may have a lower autoregulatory capacity. in acute brain injuries such as intracerebral and subarachnoid hemorrhage, and traumatic brain injuries, dynamic CA can be significantly altered in the posterior circulation. Proposed physiological mechanisms of impaired CA in the posterior circulation include: (1) Decreased sympathetic innervation of the vasculature impairing compensatory vasoreactivity; (2) Endothelial dysfunction; (3) Increased cerebral metabolic rate of oxygen consumption within the visual cortex causing CBF-metabolism (i.e., neurovascular) uncoupling; and (4) Impaired blood-brain barrier integrity leading to impaired astrocytic mediated release of vasoactive substances (e.g. nitric oxide, potassium, and calcium ions). Furthermore, more research is needed on the effects of collateral circulation, as well as the circle of Willis variants, such as the fetal-type posterior cerebral artery, on dynamic CA. Improving our understanding of these mechanisms is crucial to improving the diagnosis, prognosis, and management of various cerebrovascular disorders.

Sensitivity of Functional Arterial Spin Labelling in Detecting Cerebral Blood Flow Changes

Aims/Background Arterial spin labelling (ASL) is a non-invasive magnetic resonance imaging (MRI) method. ASL techniques can quantitatively measure cerebral perfusion by fitting a kinetic model to the difference between labelled images (tag images) and ones which are acquired without labelling (control images). ASL functional MRI (fMRI) provides quantitative perfusion maps by using arterial water as an endogenous tracer instead of depending on vascular blood oxygenation level.This study aimed to assess the number of pulsed ASL blocks that were needed to provide accurate and reliable regional estimates of cerebral blood flow (CBF) changes when participants engaged in visually guided saccade and fixation task; evaluate the localization to cortical control saccade versus fixation; investigate the relationship between the sensitivity of ASL fMRI and the number of blocks; and compare the sensitivity of blood oxygen level-dependent (BOLD) fMRI and ASL fMRI. Methods The experiment was a block-design paradigm consisting of two conditions: fixation and saccade. No response other than the eye movements of the participants was recorded during the scans. ASL and BOLD fMRI scans were conducted on all participants during the same session. The fMRI study consisted of two functional experiments: a CBF contrast was provided using the ASL sequence, and an optimized BOLD contrast was provided using the BOLD sequence. Results From group analysis in all divided blocks of ASL sessions (4, 6, 8...... 14, 16, 18......26, 28, 30), ASL yielded significant activation clusters in the visual cortex of the bilateral hemisphere from block 4. There was no false activation from block 4. No activation cluster was found by reversing analysis of block 2. Robust and consistent activation in the visual cortex was observed in each of the 14 divided blocks group analysis, and no activation was found in the eye field of the brain. The sensitivity of 4-block was found to be better than that of 8-block. More significant activation clusters of the visual cortex were found in BOLD than in ASL. No activation cluster of parietal eye field (PEF), frontal eye field (FEF) and supplementary eye field (SEF) was detected in ASL. The voxel size of the activation cluster increased with the increasing number of blocks, and the percent signal change in the activation cluster decreased with the escalating block number. The voxel size was positively correlated with the number of blocks (correlation coefficient = 0.98, p &lt; 0.0001), and the percent signal change negatively correlated with the number of blocks (correlation coefficient = –0.90, p &lt; 0.0001). Conclusion The 4-block pulsed functional ASL (fASL) presents accurate and reliable activation, with minimal time-on-task effect and little adverse impact of time, in participants engaging in visually guided saccade and fixation tasks. Despite having lower sensitivity than BOLD fMRI, ASL can determine accurate activation location. Although the time-on-task effects affect the observation for the sensitivity of ASL over task time, it is suggested that ASL fMRI may provide a powerful method for pinpointing the time-on-task effect over a long period of time.

Time-restricted eating for prevention of age-related vascular cognitive decline in older adults: A protocol for a single-arm open-label interventional trial.

Age-related cerebromicrovascular endothelial dysfunction underlies the initiation and progression of cognitive dysfunction and dementia, thus increasing the susceptibility of older adults to such conditions. Normal brain function requires dynamic adjustment of cerebral blood flow to meet the energetic demands of active neurons, which is achieved the homeostatic mechanism neurovascular coupling (NVC). In this context, therapeutical strategies aimed at rescuing or preserving NVC responses can delay the incidence or mitigate the severity of age-related cognitive dysfunction, and time-restricted eating (TRE) is a potential candidate for such a strategy. Studies have reported that TRE can improve cardiometabolic risk factors in older adults. However, the effect of TRE on cerebrovascular endothelial function remains unexplored. Thus, this protocol outlines the study procedures to test our hypothesis that a 6-month TRE regimen of 10-h eating window will improve NVC responses and endothelial function in community-dwelling older adults. This is a single-arm, open-label interventional trial. We aim to recruit 32 adults aged 55-80 years. Participants are instructed to maintain a TRE regimen of 10 h of free eating followed by 14 h of fasting for 6 months. Before and after fasting, participants are assessed for cognitive performance, peripheral micro- and macrovascular endothelial function, and NVC responses, as well as for several confounding factors, including body composition, dietary, and physical activity data. We expect that 6 months of TRE will improve NVC response and endothelial function in older adults compared with baseline, and that these improvements will be accompanied by improvements in cognitive performance. The study proposed herein will provide critical insight into a new potential therapeutical strategy for targeting age-related cognitive dysfunction. Ultimately, slowing down or alleviating cognitive decline will translate into improved quality of life and longer healthspan for aging adults. This study was prospectively registered at ClinicalTrials.gov (NCT06019195) on August 24, 2023.

Dynamic B0 field shimming for improving pseudo-continuous arterial spin labeling at 7 T.

B0 field inhomogeneity within the brain-feeding arteries is a major issue for pseudo-continuous arterial spin labeling (PCASL) at 7 T because it reduces the labeling efficiency and leads to a loss of perfusion signal. This study aimed to develop a vessel-specific dynamic B0 field shimming method for 7 T PCASL to improve the labeling efficiency by correcting off-resonance within the arteries in the labeling region. We implemented a PCASL sequence with dynamic B0 shimming at 7 T that compensates for B0 field offsets in the brain-feeding arteries by updating linear shimming terms and adding a phase increment to the PCASL RF pulses. Rapidly acquired vessel-specific B0 field maps were used to calculate dynamic B0 shimming parameters. We evaluated both 2D and 3D variants of our method, comparing their performance against the established global frequency offset and optimal encoding scheme-based corrections. Cerebral blood flow (CBF) maps were quantified before and after corrections, and CBF values from different methods were compared across the whole brain, white matter, and gray matter regions. All off-resonance correction methods significantly recovered perfusion signals across the brain. The proposed vessel-specific dynamic B0 shimming method improved the labeling efficiency while maintaining optimal static shimming in the imaging region. Perfusion-weighted images demonstrated the superiority of the 3D dynamic B0 shimming method compared to global or 2D-based correction approaches. CBF analysis revealed that 3D dynamic B0 shimming significantly increased CBF values relative to the other methods. Our proposed dynamic B0 shimming method offers a significant advancement in PCASL robustness and effectiveness, enabling full utilization of 7 T ASL high sensitivity and spatial resolution.

Therapeutic Efficacy of Tirofiban Combined With Thrombus Aspiration and Stent Thrombectomy in the Treatment of Large Vessel Occlusion Ischemic Stroke.

This research aimed to ascertain the effects of tirofiban combined with thrombus aspiration and stent thrombectomy on large vessel occlusion ischemic stroke (LVO-IS). Sixty patients with acute ischemic stroke (AIS) caused by LVO were randomized into the control group and the intervention group (n=30). Patients in the control group received thrombus aspiration combined with stent thrombectomy, while those in the intervention group were treated with tirofiban combined with thrombus aspiration and stent thrombectomy. General data, perioperative-related indicators, cerebral blood flow perfusion, coagulation function indicators, and neurological function indicators were collected, and the prognosis was observed after 3-month treatment. A comparison of symptomatic cerebral hemorrhage rate and hospital mortality rate between the 2 groups displayed no significant difference (P>0.05). The rate of revascularization in the intervention group (90.00%) was higher versus the control group (66.67%). After treatment, the mean blood flow and cerebral blood volume of the intervention group were higher and the time to peak cerebral blood flow was less versus the control group. The prothrombin time, activated partial thromboplastin time, and prothrombinogen time of the intervention group were higher, and fibrinogen was lower versus the control group. A lower National Institutes of Health Stroke Scale score was observed in the intervention group versus the control group. Tirofiban combined with thrombus aspiration and stent thrombectomy has good efficacy in LVO-IS patients.

Changes in Cerebral Hemodynamics and Progression of Subclinical Vascular Brain Disease: A Population-Based Cohort Study.

Cerebral hypoperfusion is associated with vascular brain injury and neurodegeneration, but their longitudinal relationship is largely unknown, especially in healthy older adults. We investigated the longitudinal relationship between cerebral hemodynamics and subclinical vascular brain disease in community-dwelling older adults without stroke or dementia at baseline. Participants underwent brain magnetic resonance imaging scans every 3 to 4 years between 2005 and 2016. Cerebral blood flow (CBF) was measured through 2-dimensional phase-contrast magnetic resonance imaging; the cerebrovascular resistance index (CVRi) was defined as the ratio of mean arterial blood pressure to total CBF. Simultaneous progression in subclinical brain disease was evaluated through repeated magnetic resonance imaging assessment of white matter hyperintensities (WMH), cerebral microbleeds, lacune, and brain atrophy. The longitudinal relationship was estimated using generalized estimating equations, with adjustment for age, sex, smoking habits, body mass index, systolic blood pressure (for CBF measures), lipid level, history of diabetes and cardiovascular disease, and the baseline burden of magnetic resonance imaging markers. Among 3623 older adults (mean age, 61.4±9.3 years; 54.6% women), large decreases and increases in CBF and increases in CVRi over time were associated with white matter hyperintensity progression. The risk ratios for white matter hyperintensity progression were 1.36 (95% CI, 1.19-1.55) for large decreases in total CBF (lowest quartile), 1.02 (95% CI, 0.91-1.14) for moderate decreases (second quartile), and 1.28 (95% CI, 1.14-1.45) for large increases (highest quartile), compared with stable CBF (third quartile). The corresponding risk ratios for changes in CVRi were 1.13 (95% CI, 1.00-1.30), 1.25 (95% CI, 1.09-1.43), and 1.33 (95% CI, 1.16-1.52) for the second to fourth (versus lowest) quartiles, respectively, showing a dose-response relationship. The changes in CBF also demonstrate a similar U-shaped association with the progression of brain atrophy and incident microbleeds, whereas increases in CVRi were associated with lower microbleed risk. Longitudinal changes in CBF and CVRi may capture distinct pathophysiologies linking cerebral hemodynamics to subclinical brain disease, extending beyond single-time point measurements.

Cerebral Death: Unraveling the Mystery of the Silent Mind

The permanent loss of all brain stem functions, such as breathing, awareness, and cranial nerve reflexes, is known as brain stem death (BSD), and it presents a significant medical and ethical issue. While other bodily functions, such as heart activity and circulation, can be maintained with medical intervention, BSD is defined by the cessation of brain stem activity. The key characteristic that distinguishes BSD from other conditions, such as coma or a persistent vegetative state, is the complete and irreversible loss of brain stem function—a critical control centre for basic physiological processes. Diagnosing BSD requires strict clinical criteria and diagnostic testing to confirm the full and permanent nature of the condition. This typically involves a comprehensive neurological examination, assessment of cranial nerve reflexes, and confirmation through additional tests, such as cerebral blood flow studies or electroencephalography (EEG). A diagnosis of BSD carries significant ethical and legal implications, particularly in relation to organ donation, as it often plays a role in identifying potential donors. The ethical considerations surrounding BSD include its impact on families, the distinction between death and end-of-life care, and the challenges posed by varying legal and cultural perspectives. It highlights the importance of a clear diagnosis, obtaining informed consent, and adhering to established medical protocols to uphold human dignity and ethical standards. As medical technology advances and societal views evolve, the discussion around brain stem death continues to be a critical issue in both bioethics and modern medical practice.

A Novel Self-Supervised Learning-Based Method for Dynamic CT Brain Perfusion Imaging.

Dynamic computed tomography (CT)-based brain perfusion imaging is a non-invasive technique that can provide quantitative measurements of cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT). However, due to high radiation dose, dynamic CT scan with a low tube voltage and current protocol is commonly used. Because of this reason, the increased noise degrades the quality and reliability of perfusion maps. In this study, we aim to propose and investigate the feasibility of utilizing a convolutional neural network and a bi-directional long short-term memory model with an attention mechanism to self-supervisedly yield the impulse residue function (IRF) from dynamic CT images. Then, the predicted IRF can be used to compute the perfusion parameters. We evaluated the performance of the proposed method using both simulated and real brain perfusion data and compared the results with those obtained from two existing methods: singular value decomposition and tensor total-variation. The simulation results showed that the overall performance of parameter estimation obtained from the proposed method was superior to that obtained from the other two methods. The experimental results showed that the perfusion maps calculated from the three studied methods were visually similar, but small and significant differences in perfusion parameters between the proposed method and the other two methods were found. We also observed that there were several low-CBF and low-CBV lesions (i.e., suspected infarct core) found by all comparing methods, but only the proposed method revealed longer MTT. The proposed method has the potential to self-supervisedly yield reliable perfusion maps from dynamic CT images.

Regional cerebral blood flow reflects both neurodegeneration and microvascular integrity across the Alzheimer's continuum.

Alzheimer's disease (AD) typically involves both neurodegenerative and vascular pathologies, each associated with reductions in cerebral blood flow (CBF). However, it remains unclear whether vascular and neural contributions to regional CBF can be differentiated. Using 3D background-suppressed arterial spin labeled perfusion magnetic resonance imaging, we evaluated regional CBF in a cohort of 257 participants across the AD continuum and assessed the impact of risk factors for both AD and small vessel disease (SVD) on regional CBF. Vascular risk factors (VRFs) were associated with reduced CBF in normal-appearing periventricular white matter, while amyloid positivity was associated with reduced CBF in the posterior cingulate cortex and precuneus. Putative SVD-sensitive regions in white matter exhibited diagnosis-related CBF changes comparable to those in typical AD cortical regions. Spatial patterns of hypoperfusion may differentiate AD and VRF-related effects on regional CBF. Our findings also support the contribution of SVD in AD pathogenesis. We used 3D background-suppressed pCASL MRI to evaluate CBF across the AD continuum. Putative SVD-sensitive regions in white matter exhibited diagnosis-related CBF changes. AD and/or SVD risk correlated with reduced CBF in AD and/or SVD-related regions. VRFs were associated with more widespread CBF reductions than amyloid positivity. Spatial patterns of hypoperfusion may differentiate AD and VRF-related effects.

The menopausal transition and multiple physiologic measures of early brain health in the Coronary Artery Risk Development in Young Adults study.

This study proposed to investigate the cross-sectional and longitudinal associations of menopausal status with physiologic brain magnetic resonance imaging measures. The sample included women from the Coronary Artery Risk Development in Young Adults study who self-reported their reproductive histories and participated in the brain magnetic resonance imaging substudies at the year 25 (n = 292) and year 30 (n = 258) follow-up examinations. Menopausal status was classified based on natural menstrual cycle regularity/cessation at both time points. Gray matter cerebrovascular reactivity (CVR) was calculated as mean percent change in blood oxygen level-dependent signals in activated voxels following a breath-hold challenge. Gray matter cerebral blood flow (CBF) was assessed using pseudo-continuous arterial spin labeling. Linear regression models were used to examine cross-sectional and longitudinal associations of menopausal status with gray matter CVR and CBF after adjustment for potential age-related covariates. Women were mean age 50 years at year 25; 37% were Black; and 46% were postmenopausal. Relative to premenopause or perimenopause, postmenopause was associated with lower gray matter CVR at year 30 cross-sectionally (1.86% vs 1.69%, P = 0.03, respectively) and longitudinally for women who were postmenopausal at both time points (-0.32% [95% CI, -0.63% to -0.02%]) after covariate adjustment. Mean CVR values were also lower for these women when compared with women who remained premenopausal or perimenopausal (1.71% compared with 2.04%, respectively). Menopausal status was unrelated to either concurrent or longitudinal gray matter CBF. These findings suggest that the ability of vessels to adapt in response to hypercapnia may be impaired during menopause, even within a relatively short time window.

A Multiscale Mathematical Model for Fetal Gas Transport and Regulatory Systems During Second Half of Pregnancy.

Fetal asphyxia, a condition resulting from the combined effects of hypoxia and hypercapnia, leads to approximately 900,000 annual deaths worldwide. One cause is umbilical cord compression during labor-induced uterine contractions, disrupting the transport of metabolites to and from the placenta, and resulting in asphyxia. Current fetal well-being assessment relies on monitoring fetal heart rate and uterine contractions as indicators of oxygen delivery to the brain. To enhance our understanding of this complex relationship, this study aims to develop a modular mathematical model including fetal blood gas dynamics, the autonomic nervous system, and cerebral blood flow regulation. The novelty of this study lies in the capability of the model to simulate fetal growth. These submodels are part of a larger multiscale mathematical model describing fetal circulation in the second half of pregnancy. The blood gas model realistically replicates partial oxygen and carbon dioxide pressures in umbilical arteries and veins during healthy fetal development reported in the literature. An in silico experiment is conducted to simulate umbilical cord occlusion and is compared with lamb experiments to verify the realism of the regulation models during fetal growth. Our findings suggest that premature infants are more susceptible to umbilical cord occlusion, exhibiting elevated cerebral perfusion pressure and flow. This modular mathematical model may serve as a valuable tool for testing hypotheses related to the fetal regulatory system.

The influence of yoga exercises with voluntary pulmonary ventilation changes on intracranial arterial blood flow

Introduction. Yoga breathing exercises that involve voluntary changes in pulmonary ventilation parameters can potentially influence cerebral circulation due to changes in CO2 content in arterial blood. Objective. To assess the effect of yoga breathing exercises with changes in pulmonary ventilation levels on blood flow parameters in the middle cerebral artery (MCA). Methods. The study included 21 participants, with an average age of 39.5±8.7 years, who were capable of performing yoga exercises at respiratory rates (RR) of 3–3.5/min and 1–1.5/min. For 5 minutes, participants underwent three stages: free breathing (stage 1), breathing with RR=3–3.5/min (stage 2), and breathing with RR=1–1.5/min (stage 3). During stages 2 and 3, the «full breathing» technique, which involves maximum deep inhalation and exhalation, was employed. Respiratory rate (RR), tidal volume (TI), minute ventilation (MV), end-tidal CO2 partial pressure (PetCO2), and oxygen fraction in exhaled air (FeO2) were recorded using spiro-gas analysis. Transcranial duplex scanning was used to measure peak systolic blood flow velocity (Vps), end-diastolic blood flow velocity (Vd), time-averaged maximum blood flow velocity (TAMAX), and resistance index (RI) in the right MCA. The velocity variation index (VVI) was calculated for each stage. Results. Compared to stage 1 (free breathing), stage 2 (RR = 3–3.5/min) showed an increase in MV and FeO2, a decrease in PetCO2, and reductions in Vps, Vd, and TAMAX, with an increase in RI. VVI decreased statistically insignificantly. In stage 3 (RR = 1–1.5/min), compared to stage 1, there was an increase in PetCO2, a decrease in MV and FeO2, and increases in Vps, Vd, and TAMAX, with a decrease in RI. VVI increased significantly. Conclusions. Yoga breathing exercises at respiratory rates of 3–3.5/min and 1–1.5/min result in multidirectional shifts in ventilation and gas exchange parameters, leading to changes in arterial cerebral blood flow (a decrease and increase in blood flow velocity with an increase and decrease in MV, respectively). VVI, reflecting fluctuations in blood flow velocity, increases significantly with reduced MV, likely due to the vasodilatory effect of CO2.