Search Results (374)

Organ-on-a-Chip (OOC) platforms are microfluidic systems that recreate key features of human organ physiology in vitro via controlled perfusion. Fluid mechanical stimuli strongly influence cell morphology and function, making this important for cardiovascular OOC applications exposed to pulsatile blood flow. However, many existing OOC devices employ relatively simple chamber geometries and steady inflow assumptions, which may cause non-uniform shear exposure to cells, create stagnant regions with prolonged residence time, and overlook the specific effects of pulsatile perfusion. Here, we used computational fluid dynamics (CFD) to investigate how chamber geometry and inflow conditions shape the near-wall flow environment on a cell culture surface at a matched cycle-averaged volumetric flow rate. Numerical results demonstrated that pillarized chambers markedly reduced relative residence time (RRT) versus the flat chamber, and the small pillar configuration produced the most uniform time-averaged wall shear stress (TAWSS) distribution among the tested designs. Phase-resolved analysis further showed that wall shear stress varies with waveform phase, indicating that steady inflow may not capture features of pulsatile perfusion. These findings provide practical guidance for pillar geometries and perfusion conditions to create more controlled and physiologically relevant microenvironments in OOC platforms, thus improving the reliability of cell experimental readouts. Full article

Background: Tuberculous meningitis (TBM) is a severe central nervous system infection that can lead to cerebral vasculitis and infarction. This study aimed to evaluate changes in cerebral perfusion and vasculitis on magnetic resonance imaging (MRI) before and after anti-tuberculosis treatment, focusing on both infarcted and non-infarcted brain regions and comparing them with age-matched controls. Methods: Quantitative arterial spin labeling (ASL) perfusion and black-blood vessel wall MRI were performed at diagnosis and after 3–6 months of treatment in TBM patients and healthy controls. Regions of interest included infarcted areas, the contralateral normal brain, and TBM-affected regions without infarction. Cerebral blood flow (CBF), perfusion grading, and vasculitis were assessed and correlated with clinical stage and disease severity. Results: In total, 73 TBM patients and 26 controls were included. Among the patients, 26 (35.6%) had acute infarctions, mainly in the basal ganglia and corona radiata, and 65 (89.0%) exhibited vasculitis predominantly involving anterior circulation. Pretreatment MRI showed significantly reduced CBF in infarcted regions compared with contralateral brain and controls (p < 0.05), and both contralateral and non-infarcted TBM regions also showed lower CBF than controls (p < 0.05). After treatment, CBF increased significantly in non-infarcted regions (p < 0.05), and post-treatment perfusion grade correlated with TBM stage and vasculitis severity. Conclusions: TBM-related infarcts demonstrated marked hypoperfusion, while non-infarcted regions exhibited reversible ischemic changes. ASL and vessel wall imaging can quantitatively monitor treatment response and vascular inflammation, as well as predict late infarction in TBM patients. Full article

Vitamin D deficiency is increasingly recognized as a systemic factor influencing retinal health through inflammatory, neuroprotective, and vasculotropic pathways. Evidence regarding early retinal alterations in otherwise healthy adults remains limited. This cross-sectional study evaluated 120 eyes from 60 healthy adults stratified by serum 25(OH)D levels into <30 ng/mL (n = 60) and ≥30 ng/mL (n = 60). All subjects underwent optical coherence tomography (OCT), OCT angiography (OCTA), visual field testing, and contrast sensitivity assessment. Central macular thickness (CMT), ganglion cell complex (GCC) thickness, and perfusion density in the superficial and deep capillary plexuses (SCP, DCP) were compared between groups. Vitamin-D-insufficient eyes showed significantly reduced CMT (267.66 ± 13.31 µm vs. 274.69 ± 14.96 µm; p = 0.035). GCC thinning was significant only in the inner inferior nasal sector (70.7 ± 13.14 µm vs. 76.45 ± 12.12 µm; p = 0.030), whereas other GCC sectors were comparable between groups. Perfusion density was lower in the DCP across whole, inner, and outer regions (all p < 0.001) and in the SCP inner (p = 0.027) and outer (p = 0.009) regions, while whole SCP did not differ (p = 0.065). FAZ area was numerically larger in vitamin-D-insufficient eyes but was not statistically different (p = 0.168). Functionally, retinal sensitivity decline was greater in vitamin-D-insufficient eyes (−2.89 ± 1.29 dB vs. −2.16 ± 1.04 dB; p = 0.003), and mean central sensitivity was lower (p = 0.010), whereas contrast sensitivity did not differ between groups. Serum vitamin D levels < 30 ng/mL are associated with early, subclinical, structural and microvascular retinal alterations in healthy adults, supporting a potential role of hypovitaminosis D as a modifier of retinal integrity. Full article

Background/Objectives: Motion artifacts significantly distort fluorescence measurements during surgical perfusion assessment, potentially leading to incorrect clinical decisions. This study evaluates the efficacy of automated motion compensation (MC) in quantitative indocyanine green (q-ICG) imaging to improve the accuracy of perfusion assessment. Methods: Frames from ICG perfusion assessment during 17 pancreaticoduodenectomies were analyzed. Regions of interest (ROIs) were systematically placed on each frame series, and automated MC was applied to track tissue movement. Performance was evaluated by comparing MC with surgeon-adjusted placement using multiple image quality metrics and analyzing perfusion metrics on time–intensity curves. Principal Component Analysis (PCA) was applied to explore whether image patterns could distinguish between successful and unsuccessful motion compensation. Results: Automated motion compensation successfully corrected motion artifacts in 67.5% of frame sequences, achieving comparable performance to surgeon-guided adjustments. PCA demonstrated clear separation between sufficient and insufficient corrections (AUC = 0.80). At the population level, MC did not significantly change perfusion slope (t(59) = 1.60, p = 0.11) or time-to-peak (Tmax; t(58) = 0.81, p = 0.42). Bland–Altman analysis showed a mean bias of −0.54 (SD = 3.32) for slope and 24.95 (SD = 238.40) for Tmax. At the individual level, 86.7% of slope and 79.7% of Tmax values differed by ≥10% after MC, with mean absolute percentage changes of 108.5% (median 37.8%) and 431.5% (median 65.9%), respectively. Conclusions: MC effectively reduces motion artifacts in fluorescence-guided perfusion assessment. By improving the precision of ICG-derived parameters, this technology enhances measurement reliability and represents an enabler for accurate intraoperative perfusion quantification. Full article

Excessive oxidative stress within the renal medulla is implicated in the development of hypertension, potentially modulated by renal nerve stimulation (RNS). This study examined the effects of RNS on cortical and medullary blood perfusion in Stroke-Prone Spontaneously Hypertensive Rats (SHRSP) under both normal conditions and at varying levels of oxidative stress. Male SHRSP rats were assigned to five experimental groups and subjected to RNS at different frequencies, with infusions of vehicle, tempol, tempol plus catalase (tem + cat), diethyldithiocarbamic acid (DETC), or L-nitro-arginine methyl ester (L-NAME) at the renal cortico-medullary border (CMB). Regional blood perfusion of the renal cortex and medulla (CBP and MBP, respectively) was assessed using Laser-Doppler flowmetry. RNS significantly reduced CBP and MBP by 43 ± 8% and 23 ± 4%, respectively, at 8 Hz. Co-infusion of tempol plus catalase significantly attenuated the RNS-induced reductions in both CBP and MBP. Similarly, DETC infusion mitigated RNS-induced decreases in CBP and MBP. In contrast, tempol alone and L-NAME did not protect against the RNS-induced under-perfusion of the renal cortex and medulla. The results suggest that simultaneous removal of superoxide anion and hydrogen peroxide (H₂O₂) can alleviate the reduction in renal blood perfusion caused by RNS, emphasizing a crucial role for H₂O₂ in renal hemodynamic regulation. Interestingly, DETC, which is expected to elevate superoxide anion levels, also mitigated RNS-induced under-perfusion, suggesting the presence of a potentially novel indirect protective mechanism that warrants further investigation. Full article

Background/Objectives: Diaschisis, reduced neural activity, perfusion, and metabolism in structurally intact but anatomically connected regions, is a network-level consequence of focal brain injury. Despite the extensive literature, its prevalence across imaging modalities and diaschisis subtypes has not been systematically synthesized. This review aims to identify convergent evidence for diaschisis after ischemic stroke and clarify how its detection relates to neuroanatomical disconnection, clinical factors, and imaging methods. (PROSPERO: CRD420251017909). Methods: PubMed and Embase were searched through February 2025 for studies reporting quantitative measures of diaschisis using perfusion, metabolic, or functional imaging. Pooled prevalence and modality-specific estimates were calculated. Subgroup analyses examined diaschisis subtypes, stroke severity, age, and study quality. Results: Sixty-six studies (3021 patients) were included. Overall pooled prevalence was 53% (95% CI: 47–58%). Crossed cerebellar diaschisis was most frequently studied (49%), while thalamic and other remote patterns showed comparable or higher effect sizes. Detection varied primarily by imaging modality: ASL MRI (67%) and PET (58%) showed the highest sensitivity; SPECT (53%) and CTP (49%) were intermediate; DSC-PWI had the lowest (28%). In contrast, age had no measurable effect and stroke severity only modestly increased detection, suggesting that diaschisis is driven predominantly by neuroanatomical disconnection rather than demographic or clinical variables. Egger’s tests indicated minimal publication bias. Conclusions: Diaschisis is a common manifestation of network vulnerability after ischemic stroke, determined chiefly by lesion topology and long-range anatomical connectivity. Detection depends more on imaging physiology than patient characteristics. Standardized definitions and longitudinal multimodal studies are needed to clarify its temporal evolution and clinical significance. Full article

Ultrasound-stimulated microbubble (USMB) therapy, in combination with radiotherapy (XRT), represents a promising approach to enhancing the efficacy of conventional cancer treatments by targeting tumor vasculature. Recent preclinical studies using MRI-guided focused ultrasound have demonstrated that USMB enhances radiation effects in tumor blood vessels, resulting in significantly greater tumor cell death than radiation alone. Dynamic contrast-enhanced MRI (DCE-MRI) has been instrumental in this methodology in mapping tumor perfusion heterogeneity, allowing for precise targeting of additional USMB and XRT to specific vascular regions. This study employed four advanced texture analysis methods, GLCM, GLDM, GLSZM, and NGTDM, to quantitatively assess changes in the cellular structure of prostate tumors following different treatments, including combinations of USMB and XRT targeted to low- and high-perfusion regions. Texture features, particularly those derived from GLCM, GLDM, and GLSZM, revealed significant differences in cell structure patterns across treatment groups. The GLSZM methodology was identified as the most sensitive method for detecting treatment-induced structural changes, effectively identifying regions of necrosis and varied stages of cell death. Texture-derivative analyses further highlighted intra-tumoral heterogeneity, especially in response to additional USMB + XRT treatments. These results align with findings in other tissue models, underscoring the value of texture analysis for monitoring treatment response. Full article

Background: Laser Speckle Flowgraphy (LSFG) is a non-invasive imaging technology that quantitatively evaluates retinal and choroidal blood flow by analyzing speckle patterns generated by laser light scattering. This systematic review summarizes the application of LSFG in two major degenerative retinal diseases: age-related macular degeneration (AMD) and diabetic retinopathy (DR). Methods: A comprehensive literature search (2010–2025) was conducted in PubMed, Cochrane Library and EMBASE according to PRISMA guidelines. Twenty-three studies including a total of 974 eyes (191 AMD, 783 DR) were analyzed. Results: In AMD, LSFG detected baseline reductions in choroidal and retinal perfusion in non-exudative disease, often extending beyond atrophic regions. Anti-VEGF injections produced acute reductions in MBR, particularly with brolucizumab, with partial recovery over time; drug-specific differences suggest a potential impact on geographic atrophy progression. In DR, LSFG revealed early microvascular dysfunction even in asymptomatic eyes. Retinal and choroidal MBR and blowout score correlated with HbA1c, DR severity, and inflammatory mediators. Intravitreal anti-VEGF therapy consistently reduced retinal and choroidal MBR and RFV, while conventional panretinal photocoagulation decreased choroidal flow and vascular caliber more robustly than patterned laser, reflecting oxygenation-driven VEGF modulation. Low baseline MBR predicted higher central macular thickness and reduced therapeutic response in diabetic macular edema. Conclusions: LSFG provides reproducible, rapid, and non-invasive quantitative insights into ocular hemodynamics across degenerative retinal diseases. Its integration into multimodal imaging may facilitate early diagnosis, support personalized management, and assist in the prognostic assessment of retinal and choroidal vascular disorders. Full article

At the beginning of the COVID-19 pandemic, SARS-CoV-2-positive donors were not considered eligible for organ donation. The Italian National Transplant Centre has gradually introduced measures to prevent donor-to-recipient transmission of SARS-CoV-2 infection through organ transplantation. The current national screening protocol for deceased SARS-CoV-2-positive donors recommends molecular testing of donor lower respiratory tract (LRT) samples, graft biopsies and organ perfusion fluids. The aim of the study is to describe the 3-year experience of protocol application in a northern region of Italy. From 1 January 2022 to 31 January 2025, a total of 132 samples were analyzed (29 liver biopsies, 35 kidney biopsies, 68 perfusion fluids) from 40 organ donors with an active or resolved SARS-CoV-2 infection. SARS-CoV-2 PCR on LRT samples was positive in 26/40 (65%) donors, negative in 11/40 (27.5%) cases and in the remaining 3 (7.5%) the PCR result was unknown. Overall, 65 organs were transplanted into 60 recipients. All processed graft biopsies and organ perfusion fluid samples tested negative for SARS-CoV-2 RNA. Our data suggest that the utilization of non-lung donors with resolved or active SARS-CoV-2 infections who died of other causes appears justified and safe. Full article

Orthopedic and lower limb fracture surgeries are among the most frequent emergency procedures and are commonly performed under general anesthesia (GA). Background and clinical significance: Epidemiologically, postoperative coma after GA is rare (0.005–0.08%), but delayed awakening (2–4%) and postoperative delirium or postoperative cognitive dysfunction (POCD) (15–40%) remain significant. These neurological complications increase markedly in vulnerable brain patients with psychiatric, cerebrovascular, or neurodegenerative disorders. Methods: This mechanistic narrative review synthesizes evidence from clinical and experimental studies (1990–2025) comparing the effects of general versus Regional (RA)/local (LA) or spinal anesthesia in vulnerable neuropsychiatric populations “with pre-existing brain illness” undergoing orthopedic surgery. Domains analyzed include neuropsychiatric medications effects and interactions with the GA process and with general anesthetic agents, alongside alterations in neurotransmitter modulation, cerebrovascular autoregulation, mitochondrial dysfunction, oxidative stress, redox imbalance, and neuroinflammatory activation. The review summarizes evidence on how the choice of anesthesia type influences postoperative brain outcomes in patients with known neurological conditions. Results: From previous studies, patients with psychiatric and/or chronic brain illness have a 3–5-fold increased risk of delayed emergence and up to 60% incidence of postoperative delirium. Pathophysiological mechanisms involve GABAergic overinhibition, impaired perfusion, mitochondrial energy failure, and inflammatory amplification. Regional/local and spinal anesthesia may offer physiological advantages, preserve cerebral perfusion, and lower neurological complication rates. Conclusions: General anesthesia may exacerbate pre-existing brain vulnerability, converting reversible neural suppression into irreversible dysfunction. Therefore, whenever possible, regional/local or spinal anesthesia with or without sedation should be prioritized in those neurologically vulnerable patients to reduce the length of hospital stay (LOS) and to lower postoperative neurological complications and risks in psychiatric and neurologically unstable patients. Full article

Background: This study explored the correlation between lateral ventricle volume asymmetry and cerebral blood flow (CBF). Methods: A retrospective review of 94 patients who underwent CT perfusion (CTP) and standard brain imaging was conducted. Lateral ventricle volumes and CBF across 13 vascular-based regions of interest (ROIs) were measured. Cerebral artery stenosis was identified using magnetic resonance angiography (MRA) and digital subtraction angiography (DSA). Paired t-tests, Pearson’s correlation, logistic regression, and Cox models were used to assess the relationships between lateral ventricle asymmetry, CBF differences, and their associations with cerebral artery stenosis and the risk of stroke during follow-up. Results: 94 patients were included (mean age: 60.7 years). CBF was significantly lower on the side of the larger lateral ventricle in regions supplied by the anterior cerebral artery (ACA) (Mean relative value ± SD, % = 112.3 ± 32.5, p-value = 0.0016) and middle cerebral artery (MCA) (Mean relative value ± SD, % = 123.1 ± 57.8, p-value = 0.0004). A moderate correlation was observed between lateral ventricle volume asymmetry and CBF differences across the entire cohort. Significant associations were identified between CBF differences in specific ROIs and the presence of cerebral artery stenosis (MCA: aOR = 1.026, 95% CI: 1.004–1.048, p-value = 0.019). Conclusions: Lateral ventricle asymmetry is associated with reduced CBF in specific brain regions, particularly those supplied by the ACA. CBF differences in regions supplied by the PCA are linked to increased risk of subsequent stroke during follow-up. Full article

Indocyanine green near-infrared fluorescence (ICG-NIRF) imaging is widely used to assess tissue perfusion, yet its subjective interpretation limits correlation with postoperative parathyroid function. To address this, the Workflow model for ICG-angiography integrating Standardization and Quantification (WISQ) was developed. This exploratory prospective multicenter study evaluated the reproducibility of WISQ in adults undergoing total thyroidectomy at two Dutch university centres. Patients with contraindications to ICG or prior neck surgery were excluded. Intraoperative imaging used standardized camera settings with blood volume-adjusted ICG dosing, and perfusion curves were analyzed using predefined regions of interest. Eighty patients were included. Significant inter-centre variability was observed in maximum fluorescence intensity, inflow slope, and outflow slope (n = 30). At the lead centre, outflow was the most promising predictor of postoperative hypoparathyroidism (HPT) (median −0.33 [IQR −0.49–−0.15] a.f.u./s for HPT vs. −0.68 [−0.91–−0.41], n = 17, p = 0.08), although no parameter significantly predicted HPT. Repeated ICG injections consistently produced lower maximal intensities irrespective of injection rate, and reproducible curves were achieved only when ICG was freshly dissolved at 0.5 mg/mL instead of 2.5 mg/mL. These findings indicate that ICG concentration and injection technique influence perfusion kinetics and underscore the need to update WISQ with standardized injection dilution to improve its clinical utility. Full article

Drug-resistant epilepsy affects nearly one-third of individuals with epilepsy and remains a major cause of neurological morbidity worldwide. Surgical intervention offers a potential cure, but its success critically depends on the precise identification of the epileptogenic zone and the preservation of eloquent cortical and subcortical regions. This review aims to provide a comprehensive synthesis of current evidence on the role of multimodal neuroimaging in the personalized presurgical evaluation and planning of epilepsy surgery. We analyze how structural, functional, metabolic, and electro-physiological imaging modalities contribute synergistically to improving localization accuracy and surgical outcomes. Structural MRI remains the cornerstone of presurgical assessment, with advanced sequences, post-processing techniques, and ultra-high-field (7 T) MRI enhancing lesion detection in previously MRI-negative cases. Functional and metabolic imaging, including FDG-PET, ictal/interictal SPECT, and arterial spin labeling MRI, offer complementary insights by revealing regions of altered metabolism or perfusion associated with seizure onset. Functional MRI enables non-invasive mapping of language, memory, and motor networks, while diffusion tensor imaging and tractography delineate critical white-matter pathways to minimize postoperative deficits. Electrophysiological integration through EEG source imaging and magnetoencephalography refines localization when combined with MRI and PET data, forming the basis of multimodal image integration platforms used for surgical navigation. Our review also briefly explores emerging intraoperative applications such as augmented and virtual reality, intraoperative MRI, and laser interstitial thermal therapy, as well as advances driven by artificial intelligence, such as automated lesion detection and predictive modeling of surgical outcomes. By consolidating recent developments and clinical evidence, this review underscores how multimodal imaging transforms epilepsy surgery from a lesion-centered to a patient-centered discipline. The purpose is to highlight best practices, identify evidence gaps, and outline future directions toward precision-guided, minimally invasive, and function-preserving neurosurgical strategies for patients with drug-resistant focal epilepsy. Full article

Mild traumatic brain injury (mTBI) frequently causes subtle brain changes that are difficult to detect with conventional diagnostic approaches. In this exploratory pilot study, we combined tri-exponential intravoxel incoherent motion (IVIM) and pseudocontinuous arterial spin labeling (pCASL) MRI with Multimodal Canonical Correlation Analysis and joint independent component analysis (mCCA+jICA) to identify imaging signatures distinguishing mTBI patients from healthy controls (HCs) and their associations with clinical function. Cerebral blood flow (CBF) and IVIM-derived metrics were extracted from 90 brain regions in 19 mTBI patients and 24 HCs, and multivariate components were identified using mCCA+jICA. Two independent components (IC2, IC15) showed group differences at the uncorrected level (p < 0.05) but did not survive false discovery rate (FDR) correction. IC2 correlated positively with CBF and perfusion fraction (F_p) and negatively with tissue diffusion fraction (F_s), consistent with reduced vascular integrity in mTBI, while IC15 showed similar trends. One component correlated with Glasgow Outcome Scale–Extended (GOS-E) scores (uncorrected p = 0.046). Although this study is preliminary and limited by a small sample size, our findings suggest that mTBI is associated with perfusion and microstructural alterations, particularly in subcortical regions, and demonstrate the potential value of combining IVIM and ASL within multivariate fusion frameworks to reveal patterns not captured by single-modality approaches. Full article

Background: Endothelial and microvascular dysfunction play a central role in the pathogenesis of both cardiovascular and neurodegenerative disorders. However, whether impaired peripheral endothelial function independently predicts cognitive decline, cerebral small-vessel disease (SVD) progression, or stroke remains uncertain. Methods: We conducted a systematic review and meta-analysis of prospective cohort studies assessing the prognostic value of non-invasive peripheral endothelial tests—flow-mediated dilation (FMD), peripheral arterial tonometry (PAT/EndoPAT), and sublingual microcirculatory imaging—for cognitive or cerebrovascular outcomes. Databases (PubMed, Embase, Scopus, Web of Science) were searched from inception through 30 September 2025. Study quality was appraised using the Newcastle–Ottawa Scale (NOS), and evidence certainty was graded via GRADE. Random-effects models (DerSimonian–Laird or REML) pooled hazard ratios (HRs) using inverse-variance weighting. PROSPERO-registered (CRD42025211876). Results: Fifteen prospective cohorts (n = 13,972 participants; median follow-up 4.3 years) met inclusion criteria. Across all modalities, impaired endothelial or microvascular function predicted cognitive decline, SVD progression, or cerebrovascular events (pooled HR = 1.72, 95% CI 1.38–2.14, p < 0.001; I² = 57%). Subgroup analyses confirmed consistent associations for FMD (HR = 1.59, 95% CI 1.27–1.98) and PAT/EndoPAT (HR = 1.84, 95% CI 1.40–2.41). Evidence certainty was rated moderate-to-high according to GRADE. Conclusions: Peripheral endothelial dysfunction, measured by validated non-invasive techniques, independently predicts future cognitive and cerebrovascular events. These findings support the concept of a vascular–neural continuum, suggesting that endothelial health represents a modifiable biomarker for early neurovascular risk stratification. Routine assessment of endothelial function may help identify high-risk individuals and guide preventive interventions aimed at preserving brain and vascular health. Full article