Search Results (131)

The glymphatic system has been proposed as a brain-wide pathway that promotes the exchange between cerebrospinal and interstitial fluids and facilitates the clearance of metabolic waste products, including amyloid-β and tau proteins. Diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) has emerged as a non-invasive magnetic resonance imaging technique proposed to indirectly assess glymphatic-related fluid dynamics. This systematic review evaluated the methodological consistency and clinical applicability of the ALPS index in neurodegenerative diseases. A structured search of PubMed (MEDLINE) and Web of Science identified human studies published up to January 2026 investigating DTI-ALPS in neurodegenerative conditions. Data regarding study populations, MRI acquisition parameters, image-processing methods, statistical approaches, and clinical associations were extracted and synthesized. Ten studies met the inclusion criteria. Across studies, lower ALPS index values were generally associated with cognitive impairment, amyloid burden, and disease severity, particularly in Alzheimer’s disease. Several studies incorporated multimodal biomarkers, including amyloid positron emission tomography and cerebrospinal fluid markers, thereby improving the biological interpretation of DTI-ALPS findings. However, substantial methodological heterogeneity was identified across studies, including variability in region-of-interest placement, diffusion acquisition protocols, and image-processing pipelines. Furthermore, the interpretation of diffusivity metrics as direct measures of glymphatic flow remains controversial. Current evidence suggests that DTI-ALPS may represent a promising non-invasive imaging marker of glymphatic-related alterations; however, its biological specificity and clinical applicability remain insufficiently established. Standardized acquisition protocols, harmonized analytical pipelines, and longitudinal multicenter studies are required to clarify its role in neurodegenerative disease research. Full article

Background: Carotid body tumors (CBTs) are rare neuroendocrine neoplasms whose hardness (soft vs. hard) correlates with surgical complexity and perioperative complications. This study aimed to identify predictive multimodal imaging biomarkers of CBTs’ hardness. Methods: This single-center retrospective cohort study included 82 patients with CBTs who underwent surgical resection. Preoperative multimodal imaging and clinical data were analyzed; tumor hardness was assessed via Masson-stained fibrous proportion. Multivariate logistic regression was performed to identify independent predictors. Results: The mean age of the 82 patients was 46 ± 13 years, including 37 males, with no significant intergroup differences in age or gender. Hard CBTs were associated with longer operative durations and a higher incidence of perioperative complications including pre-, intra-, and postoperative nerve and vascular injury. Multimodal imaging analysis revealed differences in signal homogeneity on T1WI and T1WI-CE sequences of MRI between soft and hard CBTs. The CBT-to-sternocleidomastoid muscle (SCM) value on T2WI (OR 0.329; 95% CI 0.151–0.591, p < 0.001) and the erosion of perivascular fat space (PFS) (OR 19.2; 95% CI 4.390–115.884, p < 0.001) were associated with the hardness of CBTs. ROC curve analysis demonstrated that an optimal cutoff value of 2.44 for the CBT/SCM ratio on T2WI predicted hard CBTs with a specificity of 100% and a sensitivity of 67.7% (PPV 100%, NPV 83.6%, AUC = 0.892). Conclusions: Preliminary findings suggest that CBT/SCM value on T2WI and PFS erosion are promising imaging biomarkers for predicting hardness. These parameters may facilitate preoperative risk prediction, though further prospective validation is required. Full article

Background/Objectives: Atrial fibrillation (AF) is the most common supraventricular arrhythmia and one of the most commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role of inflammation, endothelial disfunction and extracellular matrix (ECM) remodeling in the pathogenesis of AF. Population studies have also suggested an association between AF and cerebral small vessel disease (CSVD), with growing evidence indicating that the burden of certain markers of CSVD is greater in women. However, the association between female sex and CSVD remains poorly understood. The aim of this study was thus to investigate the role of female sex in the association between circulating biomarkers and the presence of CSVD in AF patients undergoing oral anticoagulant therapy. Methods: The Strat-AF study is an observational, prospective, single-center, hospital-based study enrolling elderly patients with AF. Results refer to 170 patients (59 women and 111 men). Recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging (MRI) and circulating biomarker assessments. Results: From a multivariate logistic regression analysis adjusted for multiple confounders, independent predictors were: in women, elevated vWF levels for the presence of lacunar infarcts [OR 3.24 (1.23–8.55), p = 0.018], elevated MMP-12, TIMP-1, TIMP-2, and TIMP-4 levels for the presence of CMBs [OR 7.76 (1.60–37.69), p = 0.021; OR 1.90 (1.02–3.52), p = 0.042; OR 2.46 (1.27–4.80), p = 0.008; and OR 2.36 (1.12–4.95), p = 0.023, respectively], elevated IL-6 and MMP-2 levels for the presence of WMH [OR 10.65 (1.31–86.67), p = 0.027; OR 3.36 (1.23–9.15), p = 0.018, respectively] and elevated MMP-12 and TIMP-2 levels for the presence of bgEPVS [OR 2.57 (1.22–5.93), p = 0.027; OR 2.15 (1.03–4.53), p = 0.043, respectively]; and in men: elevated TIMP-1 levels for the presence of WMH [OR 2.10 (1.08–4.08), p = 0.030], elevated TIMP-1 levels for the presence of bgEPVS [OR 2.20 (1.11–4.38), p = 0.025] and elevated TIMP-1 levels for SVDs positivity [OR 7.25 (2.18–24.15), p = 0.001]. Conclusions: These results from the Strat-AF study demonstrated that a complete biohumoral and instrumental assessment can jointly identify female patients with AF at higher risk of CSVD. These findings pave the way for the implementation of clinical protocols incorporating brain MRI and circulating biomarkers as potential innovative tools for an increasingly refined—and sex-specific—stratification of cardiovascular risk in AF patients undergoing oral anticoagulant therapy. Full article

Purpose: The aim of this study was to compare the contributions of putative glymphatic-related imaging indices—diffusion-weighted image analysis along the perivascular space (DWI-ALPS) index and choroid plexus volume (CPV)—and total cortical gray matter volume (TCGMV) to cognitive function in cerebral amyloid angiopathy (CAA). Methods: Forty-four CAA patients and 22 controls underwent 3.0T MRI. Cognitive function was assessed by the Mini-Mental State Examination (MMSE). The mean DWI-ALPS index, CPV/intracranial volume (ICV), and TCGMV/ICV were compared between groups; hierarchical multivariable regression and mediation analyses evaluated MMSE correlates. Results: Compared with controls, CAA showed a lower mean DWI-ALPS index and TCGMV/ICV (both adjusted p < 0.05), whereas CPV/ICV did not differ significantly after adjustment. In hierarchical multivariable regression analysis, mean DWI-ALPS index was associated with MMSE before adjustment for TCGMV/ICV (p = 0.022), but this association was attenuated after TCGMV/ICV was added to the model (p = 0.665). CPV/ICV was not associated with MMSE in either model, whereas TCGMV/ICV was independently associated with MMSE (p = 0.013). Exploratory mediation analysis suggested an indirect association between mean DWI-ALPS and MMSE via TCGMV/ICV (indirect: p = 0.023; direct: p = 0.720). Conclusions: Cortical atrophy appeared to be the strongest imaging correlate of cognitive impairment in CAA, while the association between DWI-ALPS and MMSE in multivariable models was attenuated after accounting for cortical gray matter volume. The ALPS index may provide indirect information on glymphatic-related pathways, but its biological specificity in CAA requires cautious interpretation because ALPS measurements may be influenced by underlying microstructural alterations in white matter. Full article

Circadian desynchronization is increasingly linked to metabolic, immune, neurocognitive, and oncological disease, but integrated clinical phenotyping across endocrine, microbiome, metabolic, and neuroimaging domains remains limited. We conducted a prospective, single-centre, observational study in 179 symptomatic patients referred for chronic multisystem features consistent with circadian dysregulation and 107 practically healthy controls. Circadian melatonin status was assessed using fractionated 24 h urinary 6-sulfatoxymelatonin (aMT6s) and standardized dim-light plasma sampling at daytime (14:00–16:00) and nocturnal (02:00–04:00) windows. Microbiome composition was assessed by 16S rRNA sequencing, urolithin A by targeted metabolomics, and putative glymphatic/perivascular clearance by MRI-derived DTI-ALPS index, perivascular space scoring, and white-matter-hyperintensity (WMH) volumetry. Patients showed markedly reduced nocturnal melatonin output and loss of day–night contrast (night aMT6s 10.2 vs. 40.6 ng/mL; urinary aMT6s day/night ratio 0.81 vs. 0.14; plasma nocturnal melatonin 12.7 vs. 54.4 pg/mL; all p < 0.0001), accompanied by altered cortisol day–night patterning. Patients also showed reduced microbiome diversity, depletion of Gordonibacter and Ellagibacter, lower plasma urolithin A, higher WMH volume and perivascular space scores, and a lower DTI-ALPS index. Age distributions broadly overlapped in the individual-level dataset, and key biomarkers were not significantly correlated with chronological age within the patient cohort; however, this finding is interpreted as an exploratory absence of detectable age gradient within the symptomatic cohort, not as proof of biological age-independence. Overall, the data support a coherent cross-sectional association among blunted nocturnal melatonin rhythmicity, dysbiosis/urolithin depletion, and MRI markers compatible with impaired perivascular clearance. The MGM axis framework should be regarded as hypothesis-generating; causal direction, melatonin receptor involvement, and AQP4-related mechanisms require longitudinal and mechanistic validation. Full article

Background/Objectives: Delayed neurological deficits after decompressive craniectomy may improve after cranioplasty, but quantitative imaging markers for postoperative monitoring remain limited. This study evaluated diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) as an exploratory diffusion-based marker of defect-referenced perivascular diffusivity asymmetry and examined its relationship with white matter microstructure. Methods: Forty-three adults undergoing first-time cranioplasty after decompressive craniectomy and thirty-four matched healthy controls underwent diffusion magnetic resonance imaging and neuropsychological assessment before cranioplasty; twenty-five patients were reassessed at 3 months. DTI-ALPS was quantified globally and according to defect laterality. The white matter microstructure was assessed using tract-based spatial statistics and automated fiber quantification. The associations between imaging measures and cognitive performance were also examined. Results: Global DTI-ALPS was significantly lower in patients than in controls both before cranioplasty and at 3-month follow-up, with no significant longitudinal increase. Defect-referenced hemispheric asymmetry persisted, with lower ALPS values on the affected side, and white matter abnormalities were widespread before cranioplasty and remained evident at follow-up. Associations between imaging measures and cognitive performance were not significant after multiple-comparison correction. Conclusions: DTI-ALPS may capture persistent defect-related hemispheric diffusion asymmetry after cranioplasty and provide complementary information to conventional white matter metrics. However, in patients with substantial postoperative anatomical and fiber-orientation changes, ALPS should be interpreted cautiously as an exploratory proxy of perivascular diffusivity rather than as a direct measure of glymphatic function or physiological recovery. Full article

Background and Objectives: The inner ear has traditionally been regarded as an immunoprivileged and anatomically isolated organ. However, growing interest in neuro-lymphatic interactions has raised the hypothesis that glymphatic and lymphatic mechanisms may contribute to auditory pathology and its association with cognitive dysfunction. This systematic review aimed to synthesize current human evidence regarding anatomical, imaging, and clinical correlates of glymphatic mechanisms in the inner ear and audiological pathologies, and to quantitatively evaluate currently available biomarkers. Materials and Methods: A structured search of PubMed, Scopus, and Cochrane databases was performed from inception through March 2026. Eligible studies included human investigations reporting anatomical, histopathological, or MRI-based glymphatic assessments related to inner ear disorders. Risk of bias was assessed using the Newcastle–Ottawa Scale and Joanna Briggs Institute tools. Meta-analysis was conducted for diffusion tensor image analysis along the perivascular space (DTI-ALPS) indices comparing auditory disorders with healthy controls. Results: Six studies met inclusion criteria (five cross-sectional imaging studies and one surgical histopathological case series). Histopathology demonstrated lymphatic capillaries in advanced Ménière disease. MRI studies consistently reported reduced ALPS indices and/or increased choroid plexus volume and enlarged perivascular spaces in tinnitus, congenital sensorineural hearing loss, and age-related hearing loss. Meta-analysis of five studies showed a significant reduction of ALPS index in auditory disorders compared with controls (SMD = −0.73, 95% CI −0.90 to −0.55; p < 0.001), with no heterogeneity. Glymphatic markers were frequently associated with audiological data, cognitive performance and inflammatory biomarkers. Conclusions: Human evidence supports the presence of altered central glymphatic function across diverse auditory phenotypes. Although predominantly based on indirect MRI proxies and cross-sectional data, the meta-analytic findings strengthen the biological plausibility of an auditory–glymphatic interaction. Prospective longitudinal studies are warranted to clarify causality and therapeutic implications. Full article

Background: We aimed to investigate the prevalence and clinical significance of pontine microtubular signal intensity (MSI), presumed dilated perivascular or perineural spaces, in patients with hemifacial spasm (HFS) using high-resolution MRI using proton density-weighted imaging (HR-PDI). Methods: We retrospectively analyzed 438 patients with unilateral HFS who underwent microvascular decompression (MVD) and preoperative HR-PDI. MSI was defined as a linear or curvilinear hyperintense lesion along the presumed course of the intraparenchymal facial nerve fascicles within the pons on HR-PDI. The presence and laterality of MSI were evaluated by consensus between two reviewers and classified according to their relationship to the symptomatic side of HFS as ipsilateral (same side as the facial spasm), contralateral (opposite side), or bilateral. Clinical characteristics, surgical findings, and postoperative outcomes were compared according to the presence of ipsilateral MSI. A control group of 307 subjects who underwent HR-PDI for non-central neurologic symptoms was included to assess the prevalence of MSI. Multivariable logistic regression analysis was performed to identify factors associated with immediate postoperative improvement after MVD. Results: MSI was more frequently observed in patients with HFS than in controls after adjusting age and sex (OR, 3.78; 95% CI, 2.747–5.197; p < 0.001). Ipsilateral MSI was identified in 267 of 438 patients (61.0%). Patients with ipsilateral MSI showed a significantly higher frequency of contralateral MSI (p < 0.001) and vertebralartery-related compression (p = 0.002). Immediate postoperative improvement after MVD was less frequent in patients with ipsilateral MSI than in those without MSI (77.5% vs. 86.5%, p = 0.019). Multivariable logistic regression analysis demonstrated that ipsilateral MSI was independently associated with a lower likelihood of immediate postoperative improvement (OR, 0.411; 95% CI, 0.222–0.759; p = 0.005). However, long-term surgical outcomes were not significantly different according to the presence of MSI. Conclusions: Pontine MSI on HR-PDI is more frequently observed in patients with HFS and is associated with a lower likelihood of immediate postoperative improvement and a tendency toward delayed recovery after MVD but not with poorer long-term outcomes. These findings suggest that MSI may represent microstructural or neurofluidic alterations along the pontine facial nerve pathway and may serve as an imaging marker of delayed recovery dynamics. Full article

Objective: To investigate the integrated relationship between Cerebral Small Vessel Disease (CSVD) markers and quantitative facial soft-tissue measurements in Alzheimer’s disease (AD) continuum, utilizing peripheral muscle health as a potential biomarker for systemic frailty and neurodegeneration. Methods: Retrospective analysis of 3T brain MRI data from 67 patients (AD, N = 45; Mild Cognitive Impairment [MCI], N = 22). CSVD markers were assessed using STRIVE and standardized scales (Fazekas, Potter). Facial soft-tissue metrics, including masseter and tongue volume, temporal muscle thickness (TMT), and fat infiltration (Mercuri Scale), were quantified via semi-automatic segmentation on T1-weighted sequences. Group comparisons (AD vs. MCI) used regression models adjusted for age and sex. The overall central–peripheral relationship was explored via Canonical Correlation Analysis (CCA). Results: The AD group showed a highly significant cognitive decline (MMSE: 23.2 ± 4.1 vs. 28.2 ± 1.4, p < 0.0001). Centrally, the presence of PVSs in the mesencephalic region was the most robust predictor for AD (p = 0.003). Peripherally, average masseter muscle volume was significantly lower in the AD group (p = 0.0273), and masseter fat infiltration was significantly higher (p = 0.025), supporting localized sarcopenia. The CCA demonstrated a statistically significant positive multivariate relationship (r = 0.51, Roy’s Largest Root p = 0.015) between a higher combined CSVD burden and a worse soft tissue profile across the cohort. Conclusions: Quantitative indices of facial soft tissues, particularly masseter muscle volume and quality, reflect systemic frailty and cognitive deterioration along the AD continuum. The strong central–peripheral correlation suggests that sarcopenia and CSVD are interconnected manifestations of a shared pathobiological process. These easily measurable facial markers could serve as valuable, non-invasive peripheral biomarkers, complementing traditional neuroimaging risk stratification in AD. Full article

The discovery of the glymphatic system (GS) transformed understanding of central nervous system homeostasis by revealing a brain-wide network that facilitates cerebrospinal and interstitial fluid exchange along perivascular pathways. This system clears metabolic waste and maintains the precise ionic environment required for neuronal function through the coordinated action of astrocytic aquaporin-4 channels and intact perivascular architecture. Glioblastoma multiforme (GBM), the most aggressive primary brain tumor in adults, alters physiological barriers through pathological angiogenesis, compression of perivascular spaces, depolarization of aquaporin-4 at astrocytic endfeet, and obstruction of venous and lymphatic drainage. This narrative review synthesizes current experimental and clinical literature identified through targeted searches of PubMed and Scopus to examine interactions between glioblastoma, glymphatic system dysfunction, and tumor microenvironmental changes. To minimize selection bias, studies were categorized according to evidence source and experimental design. Evidence from rodent models and advanced imaging demonstrates as tumor growth impairs glymphatic function, the resulting dysfunction promotes tumor progression by enabling accumulation of pro-tumorigenic growth factors, inflammatory mediators, and acidic metabolites, while elevated interstitial fluid pressure limits drug delivery. Impaired antigen drainage further diminishes immune surveillance, contributing to the immunosuppressive microenvironment that limits immunotherapy efficacy. A critical evaluation of these mechanisms highlights how the glymphatic system influences disease progression and suggests novel avenues for diagnostic imaging and therapeutic intervention. Although significant challenges remain in modeling human fluid dynamics, understanding these hidden networks offers a promising frontier for strategies aimed at restoring cerebral clearance and improving clinical outcomes. Full article

Background and Objectives: Enlarged perivascular spaces (ePVS) demonstrated by MRI have recently been associated with cerebral small vessel disease and glymphatic dysfunction, implicated in Parkinson’s disease (PD) pathophysiology. This study aimed to quantify the burden of ePVS in PD patients versus healthy controls and to examine associations with cognitive performance. Materials and Methods: A total of 51 participants underwent 3T MRI, including a T2-weighted sequence. Twenty-one patients with Parkinson’s disease and 21 age-matched healthy controls were included in the final analysis. The ePVS burden was assessed quantitatively by counting visible PVS in the basal ganglia and centrum semiovale, and qualitatively using Potter and Heier rating scales. Cognitive function was measured with the Montreal Cognitive Assessment (MoCA). Statistical analyses used Mann–Whitney U tests and Spearman correlations. Results: PD patients had significantly higher total PVS counts in the basal ganglia (84.8 vs. 48.0; p < 0.001) and centrum semiovale (290.6 vs. 143.9; p < 0.001). Potter scale ratings were higher in PD across regions (p ≤ 0.025). Largest per-slice PVS counts negatively correlated with MoCA scores in right basal ganglia (ρ = −0.362, p = 0.012) and bilateral centrum semiovale (right: ρ = −0.421, p = 0.003; left: ρ = −0.431, p = 0.002). Heier scale differences were significant only in the right centrum semiovale (p = 0.023). PVS diameters were larger in PD only in the centrum semiovale (right: p = 0.010; left: p = 0.040). Conclusions: In this cohort, increased ePVS burden in the basal ganglia and centrum semiovale was associated with cognitive impairment in PD patients. Qualitative and quantitative PVS assessment, notably the largest-per-slice counts, may serve as a sensitive, non-invasive imaging biomarker for neurodegeneration and cognitive decline in PD. Larger group studies and longitudinal data are needed to assess their prognostic value in the long term, as well as the development of automatic quantification applications for better reproducibility. Full article

Background: The glymphatic system, essential for brain waste clearance and neuroimmune regulation, remains underexplored in the context of bipolar disorder (BD) among young populations. Methods: Using diffusion tensor image analysis along the perivascular space (DTI-ALPS), we compared ALPS indices derived from the conventional FSL-based (cFSL) pipeline with those from the individualized ALPS (iALPS) pipeline. A cohort of young adults comprising 77 individuals with BD and 289 healthy controls was analyzed to evaluate methodological consistency and to identify disorder-specific alterations in glymphatic function. Results: The two pipelines showed only moderate agreement (Lin’s concordance correlation coefficient = 0.52–0.60), suggesting that differences in ROI placement strategies significantly affect ALPS estimation. While the cFSL pipeline detected no group differences, the iALPS pipeline identified a trend-level reduction in ALPS index in patients with BD during depressive episodes, particularly in the right hemisphere (p = 0.036, uncorrected, FDR-adjusted p = 0.071). No significant glymphatic alterations were observed in individuals with early-stage BD. Conclusions: These findings suggest that glymphatic dysfunction in psychiatric disorders may be phase-specific on illness. The use of individualized and automated analytical strategies, such as the iALPS pipeline, appears to enhance sensitivity to subtle, state-related brain changes that conventional methods may overlook. This methodological advancement provides a more biologically informed framework for future large-scale and longitudinal studies aimed at elucidating the role of glymphatic function in the pathophysiology of psychiatric disorders. Full article

Background/Objectives: The aim of this study was to investigate the effects of cranio-cervical artery stenosis (CAS) and cerebral infarction (CI) on the function of the glymphatic system (GS). Methods: Hospitalised patients with CI and/or CAS were enrolled, along with a control group. A total of 111 participants (62.68 ± 9.85 years; 37% female) were enrolled in this study. GS function was assessed using the diffusion tensor imaging analysis along with the perivascular space (DTI-ALPS) method. The influencing factors and the individual and combined effects of CI and CAS on the DTI-ALPS index were analysed. Results: Age (p = 0.024), CI (p < 0.001), and CAS (p = 0.001) were independent predictors of a lower DTI-ALPS index. There were statistically significant differences in the DTI-ALPS index among the four groups (CI, CAS, CI + CAS, control) (F(3, 107) = 91.4, p < 0.0001). The DTI-ALPS index was lower in the CI, CAS, and CI + CAS groups compared with the control group (p < 0.0001); in the CI group compared with the CAS group (p < 0.0001); and in the CI + CAS group compared with the CI group (p < 0.05). CI and CAS were found to have a significant interaction effect on the DTI-ALPS index (F(1, 107) = 6.43, p = 0.013). Conclusions: Aging, CAS, and CI independently impair GS function, with CI having a stronger effect. All three are independent predictors of GS dysfunction. Patients with CAS experience more significant GS dysfunction after suffering CI than patients without CAS. CI and CAS have a synergistic effect on GS impairment. Full article

Cerebral small vessel disease (CSVD) is a leading cause of stroke, cognitive impairment, and vascular dementia, yet disease-modifying therapeutic strategies remain limited. Emerging evidence suggests that sleep fragmentation (SF), a common and often under-recognized feature of aging and cardiometabolic disorders, plays a pivotal role in CSVD pathogenesis by disrupting the glymphatic system, the brain’s primary waste clearance pathway. Sleep-dependent glymphatic function facilitates the removal of neurotoxic metabolites and maintains neurovascular homeostasis. In contrast, SF impairs cerebrospinal fluid (CSF)–interstitial fluid (ISF) exchange, promotes perivascular space enlargement, endothelial dysfunction, blood–brain barrier (BBB) breakdown, and chronic neuroinflammation, hallmarks of CSVD. This review synthesizes current mechanistic, preclinical, and clinical evidence linking SF to glymphatic dysfunction and small vessel pathology, framing these interactions as a sleep–glymphatic–vascular continuum underlying CSVD progression and cognitive decline. We further explore the emerging therapeutic potential of tocotrienols (T3), vitamin E isoforms with potent antioxidant, anti-inflammatory, and vasculoprotective properties, as modulators of neurovascular integrity within this continuum. Although direct evidence linking T3 to glymphatic regulation remains limited, converging data support their capacity to preserve endothelial function, attenuate oxidative stress, and stabilize astrocytic and BBB dynamics, mechanisms highly relevant to glymphatic and microvascular health. By integrating sleep biology, glymphatic neuroscience, and nutritional vascular protection, this review highlights hypothesis-generating preventive and therapeutic avenues for CSVD and delineates key knowledge gaps, including the need for longitudinal human studies, standardized glymphatic imaging, objective sleep phenotyping, and interventional trials to establish causal and translational relevance. Full article

Introduction: Acute ischemic stroke demands interventions that restore perfusion and protect neurons within a narrow therapeutic window. We propose a unified theranostic platform that couples adaptive imaging, topology-aware decision-making, and immediate neuroprotective and micro-dosimetric intervention. Methods: The platform integrates three components. First, a topology-preserving MR–PET engine employs adaptive Poisson-disc sampling, partial Fourier constraints, and structured Hankel low-rank priors in a closed loop. Persistent-homology metrics quantify vascular graph uncertainty and guide subsequent k-space and PET projections, reducing acquisition time while preserving collateral topology. Second, immediate post-reperfusion delivery of glycolic acid attenuates glutamate-driven calcium influx and stabilizes mitochondrial function. Third, trace doses of sol–gel-derived, neutron-activated ⁹⁰Y₂O₃ microspheres provide sharply confined beta irradiation for micro-scale metabolic modulation. Results: In a porcine stroke model replicating the human recanalization workflow, the imaging engine maintained vascular Betti-number invariants within three percent of fully sampled reference scans while reducing acquisition time by nearly half. Glycolic acid reduced glutamate-induced intracellular calcium rise by approximately sixty percent in vitro and decreased infarct volume by thirty-eight percent in vivo. Micro-dosimetry confirmed a mean perivascular beta dose of twenty-eight grays, and histology demonstrated a forty-two percent increase in NeuN-positive neuronal survival compared with standard recanalization. Conclusions: These results demonstrate that intelligent compressed-sensing MR–PET, targeted micro-radioembolization, and glycolic acid neuroprotection can act synergistically to bridge diagnostic imaging and immediate intervention. By coupling imaging, decision-making, and therapy in a closed-loop manner and elevating topological fidelity from a reconstruction byproduct to a control variable, the proposed platform reframes MR–PET from passive diagnostics into an active, decision-driven theranostic system and establishes a foundation for future human trials. Full article