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Coronary flow reserve (CFR) and coronary artery calcium (CAC) represent functional and structural aspects of atherosclerosis. We examined the prevalence of reduced CFR and high CAC scores in three predefined groups of participants without known cardiovascular disease: (1) patients with type 2 diabetes and albuminuria; (2) patients with type 2 diabetes and normoalbuminuria; and (3) non-diabetic controls. In a cross-sectional design, cardiac (82)Rb positron emission tomography/computed tomography was conducted in 60 patients with type 2 diabetes who were free of overt cardiovascular disease and who were stratified by normoalbuminuria (<30 mg/24 h) (n = 30; age [mean ± SD] 60.9 ± 10.1 years) and albuminuria (≥ 30 mg/24 h) (n = 30; age 65.6 ± 4.8 years), and in 30 healthy, non-diabetic controls (age 59.8 ± 9.9 years). In controls, normoalbuminuric and albuminuric patients, CFR was 3.0 ± 0.8, 2.6 ± 0.8 and 2.0 ± 0.5, respectively. Reduced CFR (<2.5) was observed in 16.7%, 40.0% and 83.3% of participants, respectively, and median (interquartile range) CAC scores were 0 (0-81), 36 (1-325) and 370 (152-1,025), respectively (p for trend <0.01). After adjustment, the difference in CFR and CAC between albuminuric patients and controls remained significant (p ≤ 0.001). There were trends towards lower CFR and higher CAC scores in normoalbuminuric patients vs controls (p ≤ 0.023) and towards higher CAC scores in albuminuric vs normoalbuminuric patients (p = 0.026). In multivariate regression analysis, a higher urinary albumin excretion rate (UAER) tended to predict reduced CFR in the total population (p = 0.045). When the CAC score was added, there was also a trend (p = 0.032) towards an inverse association with reduced CFR. Type 2 diabetic patients who were free of overt cardiovascular disease had a high prevalence of coronary microvascular dysfunction, especially with concomitant albuminuria, suggesting a common microvascular impairment occurring in multiple microvascular beds. Prospective studies are needed to show the prognostic significance of this finding.

The glycocalyx is an extracellular layer lining the lumen of the vascular endothelium, protecting the endothelium from shear stress and atherosclerosis and contributes to coagulation, immune response and microvascular perfusion. The GlycoCheck system estimates glycocalyx' thickness in vessels under the tongue from perfused boundary region (PBR) and microvascular perfusion (red blood cell (RBC) filling) via a camera and dedicated software. Evaluating reproducibility and influence of examination conditions on measurements with the GlycoCheck system. Open, randomised, controlled study including 42 healthy smokers investigating day-to-day, side-of-tongue, inter-investigator variance, intraclass-correlation (ICC) and influence of examination conditions at intervals from 0-180 minutes on PBR and RBC filling. Mean (SD) age was 24.9 (6.1) years, 52% were male. There was no significant intra- or inter-investigator variation for PBR or RBC filling nor for PBR for side-of-tongue. A small day-to-day variance was found for PBR (0.012μm, p = 0.007) and RBC filling (0.003%, p = 0.005) and side-of-tongue, RBC filling (0.025%, p = 0.009). ICC was modest but highly improved by increasing measurements. Small significant influence of cigarette smoking (from 40-180 minutes), high calorie meal intake and coffee consumption was found. The latter two peaking immediately and tapering off but remained significant up to 180 minutes, highest PBR changes for the three being 0.042μm (p<0.05), 0.183μm (p<0.001) and 0.160μm (p<0.05) respectively. Measurements with the GlycoCheck system have a moderate reproducibility, but highly increases with multiple measurements and a small day-to-day variability. Smoking, meal and coffee intake had effects up to 180 minutes, abstinence is recommended at least 180 minutes before GlycoCheck measurements. Future studies should standardise conditions during measurements.

Background Transabdominal ultrasonography and transperineal ultrasonography (TPUS) appear correspond to colonoscopy (CS) for evaluating ulcerative colitis (UC) activity, but their utility in UC diagnosis remains unclear. This research compared the accuracy of TPUS and CS for assessing rectal activity and differentiating noninflammatory bowel disease proctitis from UC in pediatric cases. Methods The study is a blinded, prospective, and controlled trial. Prospectively, values of fecal calprotectin (FCP) and findings of the TPUS and CS were compared between child cases of UC and non-IBD proctitis. Findings of rectal wall thickening (RWT), rectal wall flow (RWF) on power Doppler, and microvascular signal at wall circumference (MSWC) on monochrome superb microvascular imaging assessed using TPUS were compared with the CS. Results Thirty patients with Mayo endoscopic subscore (MES) 0 to 1 UC, 57 with MES 2 to 3 UC, and 44 with proctitis were registered. Fecal calprotectin, RWF, and MSWC indicated significant differences among the groups (P < .05). Rectal wall thickening showed no significant difference between MES 0–1 and proctitis (P = .76). Rectal wall thickening and MSWC were independent predictors of endoscopic activity of UC, resulting in a sensitivity and specificity of 100% for RWT ≥4.5 mm and positive MSWC. Fecal calprotectin and RWF were independent predictors for differentiating MES 0 to 1 and proctitis, and FCP and RWT were independent predictors for differentiating MES 2 to 3 and proctitis. Sensitivity and specificity were 77.2% and 80.9%, respectively, for FCP >242.5 μg/g and RWF negative; and they were both 100% for RWT >4.1 mm and MSWC positive. Conclusions Transperineal ultrasonography with mSMI may enable the evaluation of rectal activity and differentiation of UC from non-IBD proctitis with accuracy comparable to endoscopy. Lay Summary Transperineal ultrasonography with superb microvascular imaging can differentiate ulcerative colitis from noninflammatory bowel disease proctitis and is therefore useful in distinguishing whether diarrhea and bloody stool during the treatments of ulcerative colitis are due to recurrence or infection.

ObjectivesThis study aimed to investigate the feasibility of segmentation-independent volume rendering (SI-VR) in visualising the root entry zone (REZ), and to explore the influence on the management of vascular compression syndromes (VCSs).MethodsTwo hundred and twenty patients with VCSs were recruited in this prospective study from July 2015 to May 2019. SI-VR was reconstructed based on inverted 3D fast spin echo T2WI. They were assigned to the experimental group and control group randomly. Patients in the experimental group would accept extra evaluation based on SI-VR before microvascular decompression. Image quality and diagnostic accuracy between SI-VR and 3D fast spin echo T2WI in the experimental group were compared by Mann–Whitney U test and chi-square test, separately. Interobserver agreement was performed with intraclass correlation coefficient. Postsurgical outcomes and complications between two groups were compared by chi-square test.ResultsSI-VR had a better interobserver agreement (0.82 vs 0.68) and diagnostic accuracy (95.5% vs 83.6%, p = 0.004) than that of 3D fast spin echo T2WI. Especially, significantly improved diagnostic accuracy was reached in detecting the multi-vascular branches compression (100% vs 15.4%, p < 0.001). There were fewer complications (7.1% vs 26.8%, p = 0.004) and less operation time (20.7 min vs 14.5 min, p = 0.007) but no significant difference of pain relief (p = 0.19) in the experimental group than in the control group.ConclusionsThe SI-VR method is feasible for the precise demonstration of the anatomy structure along the REZ, with high reliability and reproducibility. Unbiased pre-surgical visualisation could reduce redundant explorations and post-surgical complications in patients who undergo microvascular decompression.Key Points• Visualisation of the root entry zone by the segmentation-independent volume rendering is in accordance with the landscape by the neuro-endoscopy.• Segmentation-independent volume rendering has an advantage over 3D fast spin echo T2WI in the visualisation of multi-vascular branches compression.• Presurgical 3D visualisation of the neurovascular compression at the root entry zone leads to less postsurgical complications from the decrease of redundant exploration.

To report the incidence and features of retinal microvascular abnormalities (MVAs) occurring secondary to stereotactic radiotherapy (SRT) in a randomised double-masked sham-controlled clinical trial at 21 European sites. Two hundred and thirty participants with neovascular age-related macular degeneration (AMD) treated with at least three intravitreal antivascular endothelial growth factor (anti-VEGF) injections prior to enrolment, and demonstrating a continuing need for re-treatment. 16 Gy, 24 Gy or sham SRT. All three groups received pro re nata anti-VEGF injections if the lesion was judged to be active at review visits. Colour fundus images from baseline and 6 months and fluorescein angiograms from baseline and annual visits were graded for measures of morphological outcome and safety using a prespecified protocol with accompanying definitions to distinguish RT-related MVA from non-specific retinal vessel abnormalities that are known to occur in neovascular AMD. The main outcome measure was MVA detected by months 12, 24 and 36 after enrolment. The frequency of MVAs in the combined SRT arms was 0% in year 1, 13.1% in year 2 and 30.3% in year 3. The area of MVA was small and the mean change in visual acuity in year 2 was similar in a subset of SRT eyes with MVAs, versus those without MVAs. MVA was considered to have possibly contributed to vision loss in 2 of 18 cases with MVA in year 2, and 5 of 37 cases in year 3. Treatment with SRT is associated with development of subtle MVAs that have little or no impact on visual outcome. These findings can help clinicians recognise the retinal MVAs that occur in response to SRT.

BackgroundPrimary hyperoxaluria type 1 (PH1) is an orphan inborn error of oxalate metabolism leading to hyperoxaluria, progressive renal failure, oxalate deposition, and increased cardiovascular complications. As endothelial dysfunction and arterial stiffness are early markers of cardiovascular risk, we investigated early endothelial and vascular dysfunction in young PH1 patients either under conservative treatment (PH1-Cons) or after combined kidney liver transplantation (PH1-T) in comparison to healthy controls (Cont-H) and patients with a past of renal transplantation (Cont-T).MethodsSkin microvascular function was non-invasively assessed by laser Doppler flowmetry before and after stimulation by current, thermal, or pharmacological (nitroprussiate (SNP) or acetylcholine (Ach)) stimuli in young PH1 patients and controls.ResultsSeven PH1-Cons (6 F, median age 18.2) and 6 PH1-T (2 F, median age 13.3) were compared to 96 Cont-H (51 F, median age 14.2) and 6 Cont-T (4 F, median age 14.5). The endothelium-independent vasodilatation (SNP) was severely decreased in PH1-T compared to Cont-H. Ach, current-induced vasodilatation (CIV), and thermal response was increased in PH1-Cons and Cont-T compared to controls.ConclusionsPH1-T patients displayed severely decreased smooth muscle capacity to vasodilate. An exacerbated endothelial-dependent vasodilation suggests a role for silent inflammation in the early dysfunction of microcirculation observed in PH1-Cons and Cont-T.

ObjectivesPreoperative prediction of microvascular invasion (MVI) in patients with hepatocellular cancer (HCC) is important for surgery strategy making. We aimed to develop and validate a combined intratumoural and peritumoural radiomics model based on gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in primary HCC patients.MethodsThis study included a training cohort of 110 HCC patients and a validating cohort of 50 HCC patients. All the patients underwent preoperative Gd-EOB-DTPA-enhanced MRI examination and curative hepatectomy. The volumes of interest (VOIs) around the hepatic lesions including intratumoural and peritumoural regions were manually delineated in the hepatobiliary phase of MRI images, from which quantitative features were extracted and analysed. In the training cohort, machine-learning method was applied for dimensionality reduction and selection of the extracted features.ResultsThe proportion of MVI-positive patients was 38.2% and 40.0% in the training and validation cohort, respectively. Supervised machine learning selected ten features to establish a predictive model for MVI. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity of the combined intratumoural and peritumoural radiomics model in the training and validation cohort were 0.85 (95% confidence interval (CI), 0.77–0.93), 88.2%, 76.2%, and 0.83 (95% CI, 0.71–0.95), 90.0%, 75.0%, respectively.ConclusionsWe evaluate quantitative Gd-EOB-DTPA-enhanced MRI image features of both intratumoural and peritumoural regions and provide an effective radiomics-based model for the prediction of MVI in HCC patients, and may therefore help clinicians make precise decisions regarding treatment before the surgery.Key Points• An effective radiomics model for prediction of microvascular invasion in HCC patients is established.• The radiomics model is superior to the radiologist in prediction of MVI.• The radiomics model can help clinicians in pretreatment decision making.

The hippocampus is essential for spatial and episodic memory but is damaged early in Alzheimer’s disease and is very sensitive to hypoxia. Understanding how it regulates its oxygen supply is therefore key for designing interventions to preserve its function. However, studies of neurovascular function in the hippocampus in vivo have been limited by its relative inaccessibility. Here we compared hippocampal and visual cortical neurovascular function in awake mice, using two photon imaging of individual neurons and vessels and measures of regional blood flow and haemoglobin oxygenation. We show that blood flow, blood oxygenation and neurovascular coupling were decreased in the hippocampus compared to neocortex, because of differences in both the vascular network and pericyte and endothelial cell function. Modelling oxygen diffusion indicates that these features of the hippocampal vasculature may restrict oxygen availability and could explain its sensitivity to damage during neurological conditions, including Alzheimer’s disease, where the brain’s energy supply is decreased. The hippocampus is particularly sensitive to hypoxia but it has been difficult to study blood flow in this region. Here the authors compare the neurovascular function of the hippocampus and cortex and in awake mice, and find differences associated with microvascular structure.

BackgroundOptical coherence tomography angiography (OCTA) enables fast and non-invasive high-resolution imaging of retinal microvasculature and is suggested as a potential tool in the early detection of retinal microvascular changes in Alzheimer’s Disease (AD). We developed a standardised OCTA analysis framework and compared their extracted parameters among controls and AD/mild cognitive impairment (MCI) in a cross-section study.MethodsWe defined and extracted geometrical parameters of retinal microvasculature at different retinal layers and in the foveal avascular zone (FAZ) from segmented OCTA images obtained using well-validated state-of-the-art deep learning models. We studied these parameters in 158 subjects (62 healthy control, 55 AD and 41 MCI) using logistic regression to determine their potential in predicting the status of our subjects.ResultsIn the AD group, there was a significant decrease in vessel area and length densities in the inner vascular complexes (IVC) compared with controls. The number of vascular bifurcations in AD is also significantly lower than that of healthy people. The MCI group demonstrated a decrease in vascular area, length densities, vascular fractal dimension and the number of bifurcations in both the superficial vascular complexes (SVC) and the IVC compared with controls. A larger vascular tortuosity in the IVC, and a larger roundness of FAZ in the SVC, can also be observed in MCI compared with controls.ConclusionOur study demonstrates the applicability of OCTA for the diagnosis of AD and MCI, and provides a standard tool for future clinical service and research. Biomarkers from retinal OCTA images can provide useful information for clinical decision-making and diagnosis of AD and MCI.

s Objectives Habitat imaging allows for the quantification and visualization of various subregions within the tumor. We aim to develop an approach using diffusion-weighted imaging (DWI)–based habitat imaging for preoperatively predicting the microvascular invasion (MVI) of hepatocellular carcinoma (HCC). Methods Sixty-five patients were prospectively included and underwent multi- b DWI examinations. Based on the true diffusion coefficient ( D t ), perfusion fraction ( f ), and mean kurtosis coefficient ( MK ), which respectively characterize cellular density, perfusion, and heterogeneity, the HCCs were divided into four habitats. The volume fraction of each habitat was quantified. The logistic regression was used to explore the risk factors from habitat fraction and clinical variables. Clinical, habitat, and nomogram models were constructed using the identified risk factors from clinical characteristics, habitat fraction, and their combination, respectively. The diagnostic accuracy was evaluated using the area under the receiver operating characteristic curves (AUCs). Results MVI-positive HCC exhibited a significantly higher fraction of habitat 4 ( f 4 ) and a significantly lower fraction of habitat 2 ( f 2 ) ( p < 0.001), which were selected as risk factors. Additionally, tumor size and elevated alpha-fetoprotein (AFP) were also included as risk factors for MVI. The nomogram model demonstrated the highest diagnostic performance (AUC = 0.807), followed by the habitat model (AUC = 0.777) and the clinical model (AUC = 0.708). Decision curve analysis indicated that the nomogram model offered more net benefit in identifying MVI compared to the clinical model. Conclusions DWI-based habitat imaging shows clinical potential for noninvasively and preoperatively determining the MVI of HCC with high accuracy. Clinical relevance statement The proposed strategy, diffusion-weighted imaging–based habitat imaging, can be applied for preoperatively and noninvasively identifying microvascular invasion in hepatocellular carcinoma, which offers potential benefits in terms of prognostic prediction and clinical management. Key Points • This study proposed a strategy of DWI-based habitat imaging for hepatocellular carcinoma. • The habitat imaging–derived metrics can serve as diagnostic markers for identifying the microvascular invasion. • Integrating the habitat-based metric and clinical variable, a predictive nomogram was constructed and displayed high accuracy for predicting microvascular invasion.