White matter hyperintensity (WMH), a common magnetic resonance imaging (MRI) marker ofcerebral small-vessel disease, is associated with chronic cerebral ischemia; however, themechanistic heterogeneity of WMH remains poorly defined. This review integrates multimodalMRI findings into a mechanism-oriented framework spanning four axes: WMH versus normalappearingwhite matter (NAWM), periventricular versus deep location, lesion core versus perilesionalpenumbra, and longitudinal evolution. Periventricular WMHs are associated with blood–brainbarrier dysfunction, interstitial fluid accumulation, and venous remodeling, whereas deep WMHsare more closely associated with impaired glymphatic/perivascular clearance and enlargedperivascular spaces, and demyelination/macromolecular compromise varying by context. Theperilesional penumbra emerges as a critical transition zone, showing distance-dependent gradientsof microstructural rarefaction, extracellular fluid expansion, perfusion deficits, and reducedvascular reactivity that extend beyond fluid-attenuated inversion recovery-defined borders andrelate to subsequent lesion growth. Longitudinal data further indicate that abnormalities indiffusion, perfusion, and vascular reserve within NAWM precede new WMHs, nominating imagingbiomarkers of progression risk. This framework supports risk stratification beyond total lesionburden, links therapeutic opportunities to mechanism (e.g., blood–brain barrier integrity, glymphaticclearance, and cerebrovascular reactivity), and motivates biologically interpretable readouts forpatient selection and treatment monitoring. Looking forward, standardized spatial classification(including fine-grained, distance-informed parcellations), harmonized penumbra definitions, andintegration of multimodal MRI with pathology will be essential to validate mechanism-specificsubtypes and translate them into scalable, clinically usable endpoints.

OBJECTIVE: Traumatic anosmia is a common disorder following head injury; however, little is known regarding its neural basis and influence on the functional networks. Therefore, we aimed to investigate the functional connectivity changes in patients with traumatic anosmia compared to healthy controls using resting-state functional magnetic resonance imaging (rs-fMRI). MATERIALS AND METHODS: Sixteen patients with traumatic anosmia and 12 healthy controls underwent rs-fMRI. Differences in the connectivity of the olfactory and whole brain networks were compared between the two groups. Graph theoretical parameters, such as modularity and global efficiency of the whole brain or olfactory networks, were calculated and compared. Correlation analyses were performed between the parameters and disease severity. RESULTS: Patients with traumatic anosmia showed decreased intra-network connectivity in the olfactory network (false discovery rate [FDR]-corrected p < 0.05) compared with that in healthy controls. Furthermore, the inter-network connectivity was increased in both the olfactory (FDR-corrected p < 0.05) and whole brain networks (degree-based statistic-corrected p < 0.05) in the anosmia group. The whole brain networks showed decreased modularity (p < 0.001) and increased global efficiency (p = 0.019) in patients with traumatic anosmia. The modularity and global efficiency were correlated with disease severity in patients with anosmia (p < 0.001 and p = 0.002, respectively). CONCLUSION: Traumatic anosmia increased the inter-network connectivity observed with rs-fMRI in the olfactory and global brain functional networks. rs-fMRI parameters may serve as potential biomarkers for traumatic anosmia by revealing a more widespread functional damage than previously expected.
Biomarkers ; Brain ; Craniocerebral Trauma ; Humans ; Magnetic Resonance Imaging ; Olfaction Disorders

BACKGROUND: Carotid intima media thickness (CIMT) and the presence of carotid plaque have been used for risk stratification of cardiovascular disease (CVD). To date, however, the association between multi-directional functional properties of carotid artery and CVD has not been fully elucidated. We sought to explore the multi-directional mechanics of the carotid artery in relation to cardiovascular risk. METHODS: Four hundred one patients who underwent carotid ultrasound were enrolled between January 2010 and April 2013. A high risk of CVD was defined as more than 20% of 10-year risk based on the Framingham risk score. Using a speckle-tracking technique, the longitudinal and radial movements were analyzed in the B-mode images. Peak longitudinal and radial displacements, strain and strain rate were also measured. Beta stiffness and elastic modulus index were calculated from the radial measurements. RESULTS: Of the overall sample, 13% (52) of patients comprised the high-risk group. In multivariate logistic regression, CIMT and elastic modulus index were independently associated with a high-risk of CVD {odds ratio (OR): 1.810 [95% confidence interval (CI) 1.249–2.622] and OR: 1.767 (95% CI: 1.177–2.652); p = 0.002, 0.006, respectively}. The combination of CIMT and elastic modulus index correlated with a high-risk of CVD more so than CIMT alone. CONCLUSION: The elastic modulus index of the carotid artery might serve as a novel surrogate marker of high-risk CVD. Measurement of the multi-directional mechanics of the carotid artery using the speckle tracking technique has potential for providing further information over conventional B-mode ultrasound for stratification of CVD risk.
Biomarkers* ; Cardiovascular Diseases ; Carotid Arteries ; Carotid Intima-Media Thickness ; Elastic Modulus* ; Humans ; Logistic Models ; Mechanics ; Ultrasonography*