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In intracerebral hemorrhage (ICH) with pathology-proven etiology, we performed a systematic review and meta-analysis to elucidate the association between cerebral amyloid angiopathy (CAA) and arteriolosclerosis, and directly compared MRI and pathological changes of markers of cerebral small vessel disease (CSVD). Studies enrolling primary ICH who had received an etiological diagnosis through biopsy or autopsy were searched using Ovid MEDLINE, PubMed, and Web of Science from inception to June 8, 2022. We extracted pathological changes of CSVD for each patient whenever available. Patients were grouped into CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis subgroups. Of 4155 studies identified, 28 studies with 456 ICH patients were included. The frequency of lobar ICH (p<0.001) and total microbleed number (p=0.015) differed among patients with CAA + arteriolosclerosis, strict CAA, and strict arteriolosclerosis. Concerning pathology, severe CAA was associated with arteriolosclerosis (OR 6.067, 95% CI 1.107-33.238, p=0.038), although this association was not statistically significant after adjusting for age and sex. Additionally, the total microbleed number (median 15 vs. 0, p=0.006) was higher in ICH patients with CAA evidence than those without CAA. The pathology of CSVD imaging markers was mostly investigated in CAA-ICH. There was inconsistency concerning CAA severity surrounding microbleeds. Small diffusion-weighted imaging lesions could be matched to acute microinfarct histopathologically. Studies that directly correlated MRI and pathology of lacunes, enlarged perivascular spaces, and atrophy were scarce. Arteriolosclerosis might be associated with severe CAA. The pathological changes of CSVD markers by ICH etiology are needed to be investigated further., (© 2023. The Author(s).)

Brain arteriolosclerosis, one of the main pathologies of cerebral small vessel disease, is common in older adults and has been linked to lower cognitive and motor function and higher odds of dementia. In spite of its frequency and associated morbidity, arteriolosclerosis can only be diagnosed at autopsy. Therefore, the purpose of this work was to develop an in-vivo classifier of arteriolosclerosis based on brain MRI. First, an ex-vivo classifier of arteriolosclerosis was developed based on features related to white matter hyperintensities, diffusion anisotropy and demographics by applying machine learning to ex-vivo MRI and pathology data from 119 participants of the Rush Memory and Aging Project (MAP) and Religious Orders Study (ROS), two longitudinal cohort studies of aging that recruit non-demented older adults. The ex-vivo classifier showed good performance in predicting the presence of arteriolosclerosis, with an average area under the receiver operating characteristic curve AUC = 0.78. The ex-vivo classifier was then translated to in-vivo based on available in-vivo and ex-vivo MRI data on the same participants. The in-vivo classifier was named ARTS (short for ARTerioloSclerosis), is fully automated, and provides a score linked to the likelihood a person suffers from arteriolosclerosis. The performance of ARTS in predicting the presence of arteriolosclerosis in-vivo was tested in a separate, 91% dementia-free group of 79 MAP/ROS participants and exhibited an AUC = 0.79 in persons with antemortem intervals shorter than 2.4 years. This level of performance in mostly non-demented older adults is notable considering that arteriolosclerosis can only be diagnosed at autopsy. The scan-rescan reproducibility of the ARTS score was excellent, with an intraclass correlation of 0.99, suggesting that application of ARTS in longitudinal studies may show high sensitivity in detecting small changes. Finally, higher ARTS scores in non-demented older adults were associated with greater decline in cognition two years after baseline MRI, especially in perceptual speed which has been linked to arteriolosclerosis and small vessel disease. This finding was shown in a separate group of 369 non-demented MAP/ROS participants and was validated in 72 non-demented Black participants of the Minority Aging Research Study (MARS) and also in 244 non-demented participants of the Alzheimer's Disease Neuroimaging Initiative 2 and 3. The results of this work suggest that ARTS may have broad implications in the advancement of diagnosis, prevention and treatment of arteriolosclerosis. ARTS is publicly available at https://www.nitrc.org/projects/arts/., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hypertensive arteriopathy (HA) and cerebral amyloid angiopathy (CAA) may contribute to the development of mixed cerebral microbleeds (CMBs). Recently, the total small vessel disease (SVD) scores for HA and CAA were proposed, which are determined by a combination of MRI markers to reflect overall severity of these microangiopathies., Objective: We investigated whether or not total HA-SVD and CAA-SVD scores could be used to predict overlap of HA and CAA in patients with mixed CMBs., Methods: Fifty-three subjects with mixed CMBs were retrospectively analyzed. MRI markers (CMBs, lacunes, perivascular space, white matter hyperintensity [WMH] and cortical superficial siderosis [cSS]) were assessed. The HA-SVD score and CAA-SVD score were obtained for each subject. Anterior or posterior WMH was also assessed using the age-related white matter changes scale., Results: The two scores were positively correlated (ρ= 0.449, p < 0.001). The prevalence of lobar dominant CMB distribution (p < 0.001) and lacunes in the centrum semiovale (p < 0.001) and the severity of WMH in the parieto-occipital lobes (p = 0.004) were significantly higher in the high CAA-SVD score group. cSS was found in four patients with high CAA-SVD score who showed lobar-dominant CMB distribution and severe posterior WMH., Conclusion: Mixed CMBs are mainly due to HA. Assessing both two scores may predict the overlap of HA and CAA in individuals with mixed CMBs. Patients with a high CAA-SVD score may have some degree of advanced CAA, especially when lobar predominant CMBs, severe posterior WMH, lobar lacunes, or cSS are observed.

The high prevalence of end-stage renal disease emphasizes the failure to provide therapies to effectively prevent and/or reverse renal fibrosis. Therefore, the aim of this study was to evaluate the effect of long-term treatment with chaethomellic acid A (CAA), which selectively blocks Ha-Ras farnesylation, on renal mass reduction-induced renal fibrosis. Male Wistar rats were sham-operated (SO) or subjected to 5/6 renal mass reduction (RMR). One week after surgery, rats were placed in four experimental groups: SO:SO rats without treatment (n=13); SO+CAA: SO rats treated with CAA (n=13); RMR:RMR rats without treatment (n=14); and RMR+CAA:RMR rats treated with CAA (n=13). CAA was intraperitoneally administered in a dose of 0.23μg/kg three times a week for six months. Renal fibrosis was evaluated by two-dimensional ultrasonography and histopathological analysis. The kidneys of the RMR animals treated with CAA showed a significantly decrease in the medullary echogenicity (p<0.05) compared with the RMR rats that received no treatment. Glomerulosclerosis and arteriolosclerosis scores were significantly lower (p<0.001) in the RMR+CAA group when compared with the RMR group. There were no significant differences in interstitial fibrosis, interstitial inflammation and tubular dilatation scores between the RMR+CAA and RMR groups. These data suggest that CAA can be a potential future drug to attenuate the progression of chronic kidney disease., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Dementia is a global growing concern, affecting over 35 million people with a global economic impact of over $604 billion US. With an ageing population the number of people affected is expected double over the next two decades. Vascular cognitive impairment can be caused by various types of cerebrovascular disease, including cortical and subcortical infarcts, and the more diffuse white matter injury due to cerebral small vessel disease. Although this type of cognitive impairment is usually considered the second most common form of dementia after Alzheimer's disease, there is increasing recognition of the vascular contribution to neurodegeneration, with both pathologies frequently coexisting. The aim of this review is to highlight the recent advances in the understanding of vascular cognitive impairment, with a focus on small vessel diseases of the brain. We discuss recently identified small vessel imaging markers that have been associated with cognitive impairment, namely cerebral microbleeds, enlarged perivascular spaces, cortical superficial siderosis, and microinfarcts. We will also consider quantitative techniques including diffusion tensor imaging, magnetic resonance perfusion imaging with arterial spin labelling, functional magnetic resonance imaging and positron emission tomography. As well as potentially shedding light on the mechanism by which cerebral small vessel diseases cause dementia, these novel imaging biomarkers are also of increasing relevance given their ability to guide diagnosis and reflect disease progression, which may in the future be useful for therapeutic interventions. This article is part of a Special Issue entitled: Vascular Contributions to Cognitive Impairment and Dementia edited by M. Paul Murphy, Roderick A. Corriveau and Donna M. Wilcock., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: A variety of methods are available to assess arterial wall properties. The aim of this study was to investigate the relationship between some of the biochemical, functional and structural measurements of arterial wall characteristics., Material and Methods: The study comprised 563 elderly men at high risk of coronary heart disease. Circulating levels of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, von Willebrand factor (vWF) and tissue-type plasminogen activator antigen (tPAag) were compared with pulse wave velocity (PWV) measured by finger photoplethysmography and intima-media thickness (IMT) and plaque score of the common carotid artery., Results: Levels of ICAM-1 were significantly correlated with plaque score (r = 0.17, p<0.001). Levels of vWF were significantly correlated with plaque score (r = 0.11, p = 0.009) and PWV (r = 0.12, p = 0.007), and levels of tPAag were significantly correlated with PWV (r = 0.16, p<0.001). These associations, although generally weak, remained statistically significant after adjustment for relevant cardiovascular risk factors. PWV did not correlate significantly with IMT or plaque score., Conclusions: The limited intercorrelation between biochemical, functional and structural measurements of arterial wall properties observed in the present population indicate that the various methods reflect different aspects of the atherosclerotic process.

High-resolution imaging provides a significant means for accurate material modulus estimation and mechanical characterization. Within the realm of in vivo soft tissue characterization, particularly on small biological length scales such as arterial atherosclerotic plaques, optical coherence tomography (OCT) offers a desirable imaging modality with higher spatial resolution and contrast of tissue as compared with intravascular ultrasound (IVUS). Based on recent advances in OCT imaging and elastography, we present a fully integrated system for tissue elasticity reconstruction, and assess the benefits of OCT on the distribution results of four representative tissue block models. We demonstrate accuracy, with displacement residuals on the order of 10(-6) mm (more than 3 orders of magnitude less than average calculated displacements), and high-resolution estimates, with the ability to resolve inclusions of 0.15 mm diameter.