Background and Objectives: Blood-brain barrier (BBB) disruption has been proposed important in the pathogenesis of reversible cerebral vasoconstriction syndrome (RCVS), yet not all patients present an identifiable macroscopic BBB disruption, i.e., visible contrast leakage on contrast-enhanced T2-fluid attenuated inversion recovery (CE-T2-FLAIR) imaging. This study aimed to evaluate microscopic BBB permeability and its dynamic change in patients with RCVS. Methods: This prospective cohort implemented 3-Tesla (3T) dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We measured microscopic BBB permeability by determining the whole-brain and white matter hyperintensity (WMH) K^trans values and evaluated the correlation of whole-brain K^trans permeability with clinical and vascular parameters in transcranial color-coded sonography (TCCS). Results: In total, 176 patients (363 scans) were analyzed and separated into acute (≦ 30 days) and remission (≧ 90 days) groups based on the onset-to-exam time. Whole-brain K^trans values were similar between patients with and without macroscopic BBB disruption in either acute or remission stage. The whole-brain K^trans was significantly decreased (p < 0.001) from acute to remission stages. The WMH K^trans was significantly higher than mirror references and decreased from acute to remission stages (p < 0.001). Whole-brain K^trans correlated with mean pulsatility index (r_s = 0.5, p = 0.029), mean resistance index (r_s = 0.662, p = 0.002) and distal-to-proximal ratio of resistance index (r_s = 0.801, p < 0.001) of M1 segment of middle cerebral arteries at around 10-15 days after onset. The time-trend curve of whole-brain K^trans depicted dynamic changes during disease course, similar to temporal trends of vasoconstrictions and WMHs. Discussion: Patients with RCVS presented increased microscopic brain permeability during acute stage, even without discernible macroscopic BBB disruption. The dynamic changes in BBB permeability may be related to impaired cerebral microvascular compliance and WMHs formation.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), caused by cysteine-altering variants in NOTCH3, is the most prevalent inherited cerebral small vessel disease. Impaired cerebral interstitial fluid dynamics has been proposed as one of the potential culprits of neurodegeneration and may play a critical role in the initiation and progression of cerebral small vessel disease. In the present study, we aimed to explore the cerebral interstitial fluid dynamics in patients with CADASIL and to evaluate its association with clinical features, imaging biomarkers, and disease severity of CADASIL. Eighty-one participants carrying a cysteine-altering variant in NOTCH3, including 44 symptomatic CADASIL patients and 37 preclinical carriers, and 21 age- and sex-matched healthy control individuals were recruited. All participants underwent brain MRI studies and neuropsychological evaluations. Cerebral interstitial fluid dynamics was investigated by using the non-invasive diffusion tensor image analysis along the perivascular space method. We found that CADASIL patients exhibited significantly lower values of diffusion tensor image analysis along the perivascular space index comparing to preclinical carriers and healthy controls. For the 81 subjects carrying NOTCH3 variants, older age and presence of hypertension were independently associated with decreased diffusion tensor image analysis along the perivascular space index. The degree of cerebral interstitial fluid dynamics was strongly related to the severity of cerebral small vessel disease imaging markers, with a positive correlation between diffusion tensor image analysis along the perivascular space index and brain parenchymal fraction and negative correlations between diffusion tensor image analysis along the perivascular space index and total volume of white matter hyperintensity, peak width of skeletonized mean diffusivity, lacune numbers, and cerebral microbleed counts. In addition, diffusion tensor image analysis along the perivascular space index was a significant risk factor associated with the development of clinical symptoms of stroke or cognitive dysfunction in individuals carrying NOTCH3 variants. In CADASIL patients, diffusion tensor image analysis along the perivascular space index was significantly associated with Mini-Mental State Examination scores. Mediation analysis showed that compromised cerebral interstitial fluid dynamics was not only directly associated with cognitive dysfunction but also had an indirect effect on cognition by influencing brain atrophy, white matter disruption, lacunar lesions and cerebral microbleeds. In conclusion, cerebral interstitial fluid dynamics is impaired in CADASIL and its disruption may play an important role in the pathogenesis of CADASIL. Diffusion tensor image analysis along the perivascular space index may serve as a biomarker of disease severity for CADASIL.

In this study, a novel organic/inorganic hybrid material containing cadmium sulfide (CdS) nanoparticles was synthesized in situ by using an all π-conjugated block copolymer as both a synergistic long-range ordered structure-directing template and an efficient exciton quencher for the nanohybrid. The conducting–conducting block copolymer of poly(2,5-dihexyloxy-para-phenylene)-b-poly(3-hexyl thiophene) (PPP-P3HT) was used as a linear nanoreactor for the quantum dot synthesis to yield nanohybrids with highly ordered donor/acceptor (D/A) nanowire morphology that exhibit enhanced optoelectronic properties. The synthesized PPP-P3HT/CdS-OH nanohybrid possessed a one-dimensional D/A coaxial nanowire structure of uniform width (∼10 nm), wherein the synthesized CdS quantum dots were embedded, resulting in a display of superior long-term stability in a solution medium. By a simple drop casting process, the hybrid materials with highly ordered organic/inorganic nanochannel arrays could also be preserved in a thin film state, as evidenced by TEM and X-ray measurements, for device applications. The PPP-P3HT block copolymer exhibited significantly better hole mobility than its P3HT homopolymer counterpart. In addition, the resulting PPP-P3HT/CdS-OH hybrid systems displayed a considerably enhanced PL quench effect and shorter exciton lifetime due to efficient charge transfer between the P3HT block and the confining CdS nanoparticles in the P3HT/CdS coaxial domain of the hybrid nanowire structure. Therefore, the PPP-P3HT/CdS-OH nanohybrids can be used as bicontinuous nanochannels for efficient charge separation and charge transport, which show potential for use in future optoelectronic applications.

Objective: The aim of the study was to evaluate cerebral hemorrhage (CH) and contrast media leakage (CML or commonly synonymous with “contrast staining”) differentiation on flat-panel volume computed tomography (FPVCT) after intra-arterial mechanical thrombectomy. Methods: We evaluated patients with hyperattenuation on FPVCT after intra-arterial mechanical thrombectomy between 2018 and 2021 by multiple parameters on CT angiography, FPVCT, CT, and/or magnetic resonance imaging. Results: The CH (n = 43) versus CML (n = 24) groups revealed: (1) regional anatomical characteristics (preserved and distorted): 7 of 43 (9.6%) and 36 of 43 (83.7%) versus 22 of 24 (91.7%) and 2 of 24 (8.3%, P < 0.001); (2) thrombus in proximal two-thirds versus distal one-thirds M1 segment of middle cerebral artery (preserved and distorted): 17 of 21 (81.0%) and 4 of 21 (19.0%) versus 5 of 11 (45.5%) and 6 of 11 (54.5%, P = 0.040); and (3) average density ratio: 1.83 ± 0.65 versus 1.35 ± 0.13 (P = 0.004). Conclusions: Contrast media leakage can be differentiated from CH by preserved regional anatomical characteristics and relatively low average density ratio on FPVCT. Patients with CML who have embolism in proximal two thirds of M1 segment are more likely to develop hyperattenuation with preserved regional anatomy.