Search Results (171)

Background: Traumatic brain injury (TBI) remains a significant contributor to global mortality and long-term neurological disability. Accurate prognostic biomarkers are crucial for enhancing prognostic accuracy and guiding personalized clinical management. Objective: This review assesses the prognostic value of arterial spin labeling (ASL), a non-invasive MRI technique, in adult and pediatric TBI, with a focus on quantitative cerebral blood flow (CBF) and arterial transit time (ATT) measures. A comprehensive literature search was conducted across PubMed, Embase, Scopus, and IEEE databases, including observational studies and clinical trials that applied ASL techniques (pCASL, PASL, VSASL, multi-PLD) in TBI patients with functional or cognitive outcomes, with outcome assessments conducted at least 3 months post-injury. Results: ASL-derived CBF and ATT parameters demonstrate potential as prognostic indicators across both acute and chronic stages of TBI. Hypoperfusion patterns correlate with worse neurocognitive outcomes, while region-specific perfusion alterations are associated with affective symptoms. Multi-delay and velocity-selective ASL sequences enhance diagnostic sensitivity in TBI with heterogeneous perfusion dynamics. Compared to conventional perfusion imaging, ASL provides absolute quantification without contrast agents, making it suitable for repeated monitoring in vulnerable populations. ASL emerges as a promising prognostic biomarker for clinical use in TBI. Conclusion: Integrating ASL into multiparametric models may improve risk stratification and guide individualized therapeutic strategies. Full article

Although intracranial hypertension (ICH) has traditionally been framed as simply a numerical escalation of intracranial pressure (ICP) and usually dealt with in its clinical form and not in terms of its complex underlying pathophysiology, an emerging body of evidence indicates that ICH is not simply an elevated ICP process but a complex process of molecular dysregulation, glymphatic dysfunction, and neurovascular insufficiency. Our aim in this paper is to provide a complete synthesis of all the new thinking that is occurring in this space, primarily on the intersection of glymphatic dysfunction and cerebral vein physiology. The aspiration is to review how glymphatic dysfunction, largely secondary to aquaporin-4 (AQP4) dysfunction, can lead to delayed cerebrospinal fluid (CSF) clearance and thus the accumulation of extravascular fluid resulting in elevated ICP. A range of other factors such as oxidative stress, endothelin-1, and neuroinflammation seem to significantly impair cerebral autoregulation, making ICH challenging to manage. Combining recent studies, we intend to provide a revised conceptualization of ICH that recognizes the nuance and complexity of ICH that is understated by previous models. We wish to also address novel diagnostics aimed at better capturing the dynamic nature of ICH. Recent advances in non-invasive imaging (i.e., 4D flow MRI and dynamic contrast-enhanced MRI; DCE-MRI) allow for better visualization of dynamic changes to the glymphatic and cerebral blood flow (CBF) system. Finally, wearable ICP monitors and AI-assisted diagnostics will create opportunities for these continuous and real-time assessments, especially in limited resource settings. Our goal is to provide examples of opportunities that exist that might augment early recognition and improve personalized care while ensuring we realize practical challenges and limitations. We also consider what may be therapeutically possible now and in the future. Therapeutic opportunities discussed include CRISPR-based gene editing aimed at restoring AQP4 function, nano-robotics aimed at drug targeting, and bioelectronic devices purposed for ICP modulation. Certainly, these proposals are innovative in nature but will require ethically responsible confirmation of long-term safety and availability, particularly to low- and middle-income countries (LMICs), where the burdens of secondary ICH remain preeminent. Throughout the review, we will be restrained to a balanced pursuit of innovative ideas and ethical considerations to attain global health equity. It is not our intent to provide unequivocal answers, but instead to encourage informed discussions at the intersections of research, clinical practice, and the public health field. We hope this review may stimulate further discussion about ICH and highlight research opportunities to conduct translational research in modern neuroscience with real, approachable, and patient-centered care. Full article

Blood–brain barrier (BBB) dysfunction is a hallmark of cerebral small vessel disease (cSVD). This study aimed to identify a mouse model that replicates BBB impairment and shares key cSVD risk factors. Transgenic db/db and LDLr^−/−.Leiden mice, both prone to obesity and hypertension, were compared to C57BL/6J controls. BBB leakage was assessed using DCE-MRI and sodium fluorescein (NaFl); cerebral blood flow (CBF) by MRI. Dyslipidemia and vascular inflammation were measured by plasma tests. Tight junction integrity, endothelial dysfunction (glucose transporter 1, GLUT-1) and neuroinflammation were evaluated with immunohistochemistry and PCR. Both transgenic models developed an obese phenotype with hyperinsulinemia, but only LDLr^−/−.Leiden mice showed human-like dyslipidemia. When fed a high-fat diet (HFD) or HFD plus cholesterol, LDLr^−/−.Leiden mice showed reduced CBF, endothelial dysfunction (lowered GLUT-1), elevated vascular inflammation (ICAM-1, VCAM-1, S-selectin), and BBB leakage, as evidenced by DCE-MRI and NaFl, together with reduced ZO-1 and claudin-5 expression. Contrastingly, db/db mice showed endothelial dysfunction without BBB leakage. Neuroinflammation (IBA-1, GFAP) was observed only in LDLr^−/−.Leiden groups, consistent with BBB disruption. These findings indicate that LDLr^−/−.Leiden mice, but not db/db mice, are a promising translational model for studying BBB dysfunction in cSVD, offering insights into disease mechanisms and a platform for therapeutic development. Full article

MRI perfusion is used to diagnose and monitor neurological conditions such as brain tumors, stroke, dementia, and traumatic brain injury. Dynamic Susceptibility Contrast (DSC) is the most widely available quantitative MRI technique for perfusion imaging. Even in its most basic implementation, DSC MRI provides critical hemodynamic metrics like cerebral blood flow (CBF), blood volume (CBV), mean transit time (MTT), and time between the peak of arterial input and residue function (Tmax), through the dynamic tracking of a gadolinium-based contrast agent. Notwithstanding its high clinical importance and widespread use, the reproducibility and diagnostic reliability are impeded by a lack of standardized pre-processing protocols and quality controls. A comprehensive literature review and the authors’ aggregated experience identified common DSC MRI artefacts and corresponding pre-processing methods. Pre-processing methods to correct for artefacts were evaluated for their practical applicability and validation status. A consensus on the pre-processing was established by a multidisciplinary team of experts. Acquisition-related artefacts include geometric distortions, slice timing misalignment, and physiological noise. Intrinsic artefacts include motion, B₁ inhomogeneities, Gibbs ringing, and noise. Motion can be mitigated using rigid-body alignment, but methods for addressing B₁ inhomogeneities, Gibbs ringing, and noise remain underexplored for DSC MRI. Pre-processing of DSC MRI is critical for reliable diagnostics and research. While robust methods exist for correcting geometric distortions, motion, and slice timing issues, further validation is needed for methods addressing B₁ inhomogeneities, Gibbs ringing, and noise. Implementing adequate mitigation methods for these artefacts could enhance reproducibility and diagnostic accuracy, supporting the growing reliance on DSC MRI in neurological imaging. Finally, we emphasize the crucial importance of pre-scan quality assurance with phantom scans. Full article

Background: Overactive bladder (OAB) has been linked to abnormal cerebral blood flow (CBF) and functional connectivity (FC). However, findings related to CBF and FC changes in OAB remain inconsistent across the literature. Methods: This feasibility study employed arterial spin labeling (ASL) to investigate abnormal CBF and posterior cingulate cortex (PCC) FC in individuals with OAB, both at rest and during bladder filling. ASL images were collected from twenty-two female participants (twelve with OAB and ten healthy controls) at bladder filling volumes of 0, 50, 100, 200, 350, and 500 mL. For OAB participants, scans were obtained both at baseline and following a single-session treatment. ASL images were categorized into low-urge and high-urge conditions based on participants’ subjective urge rating during bladder filling. A flexible factorial design was implemented with three factors: subject, group (control, OAB at baseline, and OAB posttreatment), and urge state (low vs. high). Results: Compared to controls, OAB participants exhibited significant decreases in ΔCBF (high urge minus low urge) in the medial prefrontal cortex and increases in ΔCBF in the supramarginal region. Additionally, ΔPCC FC with the insula was reduced in OAB participants. Posttreatment, OAB participants showed increased ΔPCC FC with the postcentral and parietal (PocP), regions associated with the sensorimotor network. Notably, changes in ΔPCC-PocP FC were associated with improvements in OAB symptoms. Conclusions: These findings support the feasibility of using ASL to probe dysfunctional brain–bladder control mechanisms and treatment-related changes in OAB participants, highlighting the involvement of sensory processing and attention regulation in this condition. Full article

Background/Objectives: Assessment of the hemodynamic status of the brain in patients with cerebrovascular diseases is crucial for providing valuable clinical information. Various magnetic resonance perfusion sequences are used in studies, and one of the current challenges is comparing methods utilizing exogenous and endogenous contrast. This meta-analysis aimed to evaluate the correlation between arterial spin labeling (ASL)-derived perfusion parameters and those obtained by dynamic susceptibility contrast (DSC) perfusion in stroke and steno-occlusive diseases. Methods: A systematic review and meta-analysis were conducted, including 14 studies that reported correlation coefficients between perfusion MRI sequences in the assessment of stroke or steno-occlusive diseases. The correlation between ASL-derived cerebral blood flow (ASL-CBF) and DSC-derived cerebral blood flow (DSC-CBF) was analyzed, considering different magnetic field strengths (1.5 T and 3.0 T), sequence types, and brain regions. Additionally, real and normalized data were compared. Results: A moderate positive correlation was found between ASL-CBF and DSC-CBF (R = 0.464). Subgroup analysis demonstrated that ASL-CBF and DSC-CBF correlated at 3.0 T (R = 0.401) and 1.5 T (R = 0.700). No significant differences were observed in correlation coefficients based on sequence type or brain region. Normalized data demonstrated a higher correlation coefficient compared to real data (Rreal = 0.393, Rnorm = 0.496). Additionally, the correlation coefficient between ASL-CBF and DSC-derived mean transit time (DSC-MTT) for all included studies was R = −0.422. Conclusions: ASL-derived perfusion parameters demonstrate moderate-to-high agreement with DSC perfusion parameters in stroke and steno-occlusive patients. These findings support the potential utility of ASL as a non-invasive alternative to DSC perfusion imaging in clinical and research settings. Full article

Background: Despite the success of transcatheter aortic valve repair (TAVR) over the past years, its impact on global and cerebral hemodynamics remains largely unexplored. Changes in cerebral blood flow may be associated with delirium, which may occur in 26 to 29% of cases. We aimed to examine the relationships between global hemodynamic parameters and cerebral parameters in patients who underwent TAVR and their impact on postinterventional delirium. Methods: Patients scheduled for TAVR were enrolled after obtaining written informed consent. Patients received light sedation according to standard procedures. Cerebral blood flow (CBF) was measured with a noninvasive near-infrared spectroscopy-based method using intravenous indocyanine green injection. CBF measurements were taken at the beginning of the TAVR procedure and after the valve was in place. Patients were screened for delirium using CAM-ICU and NuDESC tests before and after intervention. Results: A total of 52 of 60 patients remained for analysis. Thirteen patients (25%) developed delirium. Mean arterial pressure (MAP) remained unchanged, while cardiac output increased after TAVR by 44%. CBF also increased after TAVR. No significant difference was observed in CBF changes between the groups with and without delirium. A linear mixed model analysis revealed a linear relationship between CO and CBF but not between MAP and CBF. In an exploratory analysis, decreased cerebral oxygenation and increased deoxygenated hemoglobin, as measured by NIRS after TAVR, were associated with delirium. Conclusions: The results confirm that CO is an independent factor in CBF, while CBF changes per se are not linked to delirium. However, we found a mismatch between CBF and regional cerebral parameters, which may reflect cerebral metabolism and its relation to the development of delirium. This remains to be confirmed by further studies. Full article

Background/Objectives: Orthostatic intolerance is prevalent in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and is caused by an abnormal reduction in cerebral blood flow (CBF). In healthy controls (HCs), CBF is regulated complexly, and cardiac output (CO) is an important determinant of CBF. A review in HC showed that a 30% reduction in CO results in a 10% reduction in CBF. In contrast, we showed in ME/CFS patients with a normal HR (HR) and blood pressure response during a tilt test that CO and CBF decreased to a similar extent. The relation between CO and CBF in ME/CFS patients with postural orthostatic tachycardia syndrome (POTS) is unknown. Therefore, the aim of this study is to assess the relation between CBF and CO, in ME/CFS patients with POTS. The methods used in this retrospective study analyze this relation in a large group of patients. We also analyzed the influence of clinical data. A total of 260 ME/CFS patients with POTS underwent tilt testing with measurements of HR, BP, CBF, CO, and end-tidal PCO₂. We measured CBF using extracranial Doppler flow velocity and vessel diameters obtained with a General Electric echo system, and suprasternal aortic flow velocities were measured using the same device. We recorded end-tidal PCO₂ using a Nonin Lifesense device. Results: End-tilt HR and the HR increase were significantly higher in the patients with a %CO reduction ≥ −15% than in the other group. End-tilt CO was higher and the %CO reduction was lower in patients with %CO reduction ≥ −15% than in the other group. CBF data (supine, end-tilt and the %CBF reduction) were not different between the two patient groups. The use of HR increases and %SV reductions were not as discriminative as the %CO reduction. Conclusions: In ME/CFS patients with POTS during tilt testing with measurements of both the CO and the CBF, two different patterns were observed: (1) appr. two-thirds of patients had an almost 1:1 relation between the %CBF reduction and the %CO reduction. (2) Appr. one-third of patients showed a limited reduction in CO together with a substantial increase in HR. In these patients, there was no relation between the CO and CBF reduction. These data suggest the presence of a hyperadrenergic response. Full article

Background/Objectives: The interplay between the gut microbiome (GMB) and neurovascular function in neurodegeneration is unclear. The goal of this proof-of-concept, cross-sectional study is to identify relationships between the GMB, neurovascular functioning, and cognition in amnestic mild cognitive impairment (aMCI), the prototypical prodromal symptomatic stage of Alzheimer’s disease (AD). Methods: Participants (n = 14 aMCI and 10 controls) provided fecal samples for GMB sequencing (16S and shotgun metagenomics), underwent MRI, and completed cognitive testing. Cerebral vascular reactivity (CVR), cerebral blood flow (CBF), and arterial transit time (ATT) were assessed. Statistical analyses evaluated the relationships between discriminatory taxa, cerebrovascular metrics, and cognition. Results: Sequencing revealed differentially abundant bacterial and viral taxa distinguishing aMCI from controls. Spearman correlations revealed that bacteria known to induce inflammation were negatively associated with CVR, CBF, and cognition, and positively associated with ATT. A reciprocal pattern emerged for the association of taxa with gut health. Conclusions: Our results provide preliminary evidence that pro-inflammatory gut bacterial and viral taxa are associated with neurovascular dysfunction and cognitive impairment in prodromal AD, highlighting their potential as candidate microbial biomarkers and targets for early intervention. Full article

Vascular dysfunction frequently coexists with neurodegenerative disorders such as dementia and Alzheimer’s disease (AD) in older individuals; however, the cause-and-effect relationship remains unclear. While AD is primarily characterized by neural tissue degeneration, emerging evidence suggests that aging-induced vascular dysfunction contributes to both the onset and progression of cognitive impairment and dementia by decreasing cerebral blood flow (CBF) and disrupting the blood–brain barrier (BBB). This challenges the traditional notion and underscores vascular dysfunction as an early pathogenic stimulus; thus, targeting vascular pathologies could be a promising strategy to slow dementia progression and potentially prevent AD. Conversely, aging-related neurodegeneration exacerbates vascular dysfunction, accelerating dementia pathology through oxidative stress and inflammation as well as deposition of neurotoxic substances such as beta-amyloid (Aβ) and tau in vascular walls. This bidirectional interaction creates a vicious cycle that worsens cognitive decline, underscoring the complexity of these diseases. This review aims to highlight recent advances in research on the mechanisms of aging-related vascular dysfunction in neurodegenerative diseases, focusing on vascular contributions to cognitive impairment and dementia (VCID) and AD. Additionally, we will explore the reciprocal effects and intricate relationship between vascular dysfunction and neurodegenerative pathologies, enhancing our understanding of relative disease pathogenesis and guiding the development of innovative prevention and treatment strategies. Full article

Assessment of cerebrovascular function is crucial for managing neurological disorders, with cerebral blood flow (CBF) measurement being key. Single photon emission computed tomography (SPECT), a traditional method, uses radiation exposure. Blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) with carbon dioxide (CO₂) is a non-invasive cerebrovascular reactivity (CVR) alternative, but direct SPECT-MRI CO₂ comparisons for MRI’s replacement potential are limited. This study directly compared CVR from SPECT and MRI CO₂ in nine healthy participants. Delay-based MRI (tcMRI) with stimulus timing correction was analyzed alongside conventional MRI. Results showed no significant CVR differences between SPECT and tcMRI (p = 0.688) or SPECT and conventional MRI (p = 0.813), indicating comparable overall CVR. However, tcMRI significantly differed from conventional MRI (p = 0.016) and showed a greater similarity to SPECT. Regionally, the largest CVR differences were observed between tcMRI and conventional MRI, particularly in the cingulate cortex, frontal lobe, and basal ganglia. These discrepancies suggest that tcMRI may capture subtle CVR abnormalities not detected by conventional MRI. The findings support the clinical utility of CO₂-MRI, especially with stimulus timing correction, as a safe, repeatable, and radiation-free alternative to SPECT. In particular, tcMRI may offer advantages for repeated CVR assessments in long-term clinical monitoring. Full article

Background. Statins appear to be useful in patients with acute ischemic stroke. Our aim was to evaluate the association between premorbid statin treatment and CT perfusion characteristics of acute ischemic stroke. Methods. A retrospective analysis of patients with acute stroke secondary to occlusion of large vessels in the anterior circulation was performed to assess collateral flow, ischemic core volume, and ischemic penumbra using CT angiography and CT perfusion maps. Fisher’s exact test was used to compare baseline characteristics of patients in the two groups. The Wilcoxon rank-sum test for independent groups was used to compare all variables obtained for the two different groups with and without statin use. Results. We identified 61 patients, including 29 treated with statins and 32 not treated with statins before stroke onset matched by age, gender, and vascular risk factors except for hypercholesterolemia. The statin group showed lower National Institutes of health Stroke Scale scores at onset (14 ± 6.1 vs. 16 ± 4.5; p = 0.04) and lower volumes of brain tissue characterized by impaired cerebral blood flow (CBF), cerebral blood volume (CBV), and ${\mathrm{T}}_{\mathrm{m}\mathrm{a}\mathrm{x}}^{9.5-25\mathrm{s}}$; otherwise, no statistically significant difference was found in the volume of the ${\mathrm{T}}_{\mathrm{m}\mathrm{a}\mathrm{x}}^{16-25\mathrm{s}}$ between the two groups. Conclusions. Premorbid statin treatment is associated with a favorable imaging condition of acute ischemic stroke in terms of ischemic core and ischemic penumbra volume. Full article

Background and Objectives: Carotid artery stenosis is a significant risk factor for ischemic stroke due to impaired cerebral blood flow (CBF). Even asymptomatic unilateral stenosis can induce subclinical cerebrovascular changes, potentially affecting both hemispheres through collateral circulation. This study aimed to systematically assess cerebral perfusion in asymptomatic individuals with unilateral carotid artery stenosis by comparing ipsilateral and contralateral hemispheres with healthy controls, challenging the assumption that the contralateral hemisphere remains unaffected. Materials and Methods: This cross-sectional study included 114 participants, comprising 54 asymptomatic individuals (mean age 65.5) with significant unilateral carotid stenosis and 60 age-matched controls (mean age 64.8). Cerebral perfusion was assessed using 1.5T Magnetic Resonance Imaging (MRI) with pseudo-continuous arterial spin labeling (pCASL). CBF was measured bilaterally in four predefined middle cerebral artery (MCA) regions: precentral gyrus, lentiform nucleus, insular cortex, and temporal cortex. Statistical analyses included multivariate analysis of variance (MANOVA), analysis of variance (ANOVA), paired t-tests, and discriminant analysis (DA). Results: Significant bilateral reductions in CBF were observed in individuals with carotid stenosis compared to controls (MANOVA and ANOVA, p < 0.001). The greatest perfusion deficit was in the ipsilateral insular cortex (49.88 ± 10.83 mL/100 g/min), followed by intermediate contralateral perfusion (51.49 ± 8.86 mL/100 g/min) and higher control values (58.78 ± 10.44 mL/100 g/min). DA indicated the insular cortex as the region with the highest discriminative contribution (64.7%). Conclusions: Unilateral carotid artery stenosis in asymptomatic individuals is associated with significant bilateral cerebral hypoperfusion, suggesting widespread hemodynamic effects. Pronounced perfusion deficits in the insular cortex underline its vulnerability. The observed contralateral perfusion reductions challenge the traditional use of the contralateral hemisphere as a reference standard, underscoring the need for comprehensive perfusion assessment in carotid artery disease. Full article

Dysphagia is a serious complication of stroke, yet effective pharmacological treatments remain limited. This study investigated the effects of FAD012 (3,5-dimethyl-4-hydroxy cinnamic acid), a synthetic derivative of ferulic acid (FA), on cerebral damage and swallowing dysfunction in a rat model of bilateral common carotid artery occlusion (2VO). Sprague–Dawley rats were orally administered FAD012 (3 or 10 mg/kg), FA (10 mg/kg), or 0.5% carboxymethyl cellulose (CMC, suspension vehicle) starting one week before 2VO. Two weeks after 2VO surgery, which was performed under isoflurane anesthesia, reflex swallowing was assessed by electromyographic recordings of the mylohyoid muscle under urethane anesthesia. Two weeks after 2VO, cerebral blood flow (CBF) declined to approximately 40% of baseline, and the number of reflex swallowing responses was significantly reduced in the CMC group. Additionally, 2VO induced O₂⁻ production, apoptotic cell death in the striatum, and a reduction in tyrosine hydroxylase expression. Substance P (SP) levels in the laryngopharyngeal mucosa, positively regulated by dopaminergic signaling in the basal ganglia, also decreased. FAD012 (10 mg/kg) effectively prevented the 2VO-induced reduction in CBF, enhanced the reflex swallowing, and preserved the dopamine-SP system. Notably, FAD012 exerted significantly stronger effects than FA at the same dose. These findings suggest that FAD012 maintains CBF under cerebral hypoperfusion and enhances the swallowing reflex by maintaining neuronal function in the striatal and laryngopharyngeal regions of 2VO rats. Full article

Background/Objectives: In neurocritical care, usually, the only continuous measurement of brain pathophysiology is intracranial pressure (ICP). The objective of this study was to find the relationship between cerebral blood flow (CBF) and parameters usually measured in neurocritical care, mainly central venous pressure and ICP. Methods: If the venous outflow of the CBF is considered, the CBF is controlled only by two parameters, the rICP (the ICP minus the venous blood pressure in the venous sinus at its outflow) and the Rv (the flow resistance of the soft-walled veins). For the rICP, the sinus blood pressure can be calculated from the central venous pressure (measured at the same horizontal level as the ICP) and the cervical venous flow resistance. For the Rv, the systolic ICP increase indicates the systolic arterial inflow volume, which then flows out before the diastole. The mean ICP increase divided by the mean outflow of the increased blood volume gives the Rv. This method of calculating the CBF by dividing the rICP by the Rv was named CBF(1). For validation of CBF(1), data from nine subjects in an open study were used. The data were ICP and MR blood flow measurements of arterial inflow and jugular vein outflow. Since the rICP, Rv, and CBF were unknown, an iterative method was needed to calculate these parameters. Results: The observed Rv and rICP values showed a close correlation, which indicated that CBF was dependant on the rICP only. Consequently, the comparison between the data in the study of the nine subjects, and the calculated values from CBF(1), boiled down to a comparison between the supine ICP values and the calculated rICP. The comparison showed that the rICP and supine ICP had highly significant similarity, and that the CBF(1) method was validated. Conclusions: A method for CBF measurement from ICP data in neurocritical care was found. Full article