The Evolution of the Bone Turnover Marker in Patients Following Recovery from Diabetic Ketoacidosis.

The aim of the study was to investigate whether the biomarkers for bone turnover could rapidly recover during the period of diabetic ketoacidosis (DKA). Bone turnover biomarkers, including 25-hydroxyvitamin D3, N-terminal middle molecular fragment of osteocalcin (NMID), and ß-C terminal cross-linking telopeptide of type 1 collagen were evaluated using in-patient data (n=627) from Shanghai Pudong Hospital from 2018-2022. The comparison was performed between type 2 diabetes (T2D only) (n=602) and DKA (n=25), in which we checked the bone turnover markers at pre-treatment and recovery. After matching by body mass index (BMI), we found that except for 25-OH-VitD3, the age difference, indices of glucose metabolism, and bone turnover were significant between the 2 groups (p<0.05). We found only a significant restoration of NMID (p<0.001). NMID and ß-CTX, when compared with T2D, showed overt distinction between recovery and T2D (p<0.05). In addition, the investigations demonstrated a substantial difference between 25-OH-VitD3 in males and NMID in females, regardless of age (p<0.05). Multilinear regression analysis revealed that 2 hours postprandial plasma C-peptide was an independent predictor of the NMID in both pre-treatment (ß=0.58, p=0.003) and recovery (ß=0.447, p=0.025), although sex was significant in pre-treatment (ß=-0.444, p=0.020). Finally, we found that only age variation affected DKA's fasting plasma glucose level (p<0.05). The study revealed that the bone turnover of DKA is significantly different in pre-treatment and recovery; however, NMID might recover quickly if the patients received appropriate treatment. Importantly, pancreatic function plays a critical role in changing bone turnover biomarkers.

The Neuronal and Non-Neuronal Pathways of Sodium-Glucose Cotransporter-2 Inhibitor on Body Weight-Loss and Insulin Resistance.

With the emergence of sodium-glucose cotransporter 2 inhibitors (SGLT2i), the treatment of type 2 diabetes mellitus (T2DM) has achieved a new milestone, of which the insulin-independent mechanism could produce weight loss, improve insulin resistance (IR) and exert other protective effects. Besides the well-acknowledged biochemical processes, the dysregulated balance between sympathetic and parasympathetic activity may play a significant role in IR and obesity. Weight loss caused by SGLT-2i could be achieved via activating the liver-brain-adipose neural axis in adipocytes. We previously demonstrated that SGLT-2 are widely expressed in central nervous system (CNS) tissues, and SGLT-2i could inhibit central areas associated with autonomic control through unidentified pathways, indicating that the role of the central sympathetic inhibition of SGLT-2i on blood pressure and weight loss. However, the exact pathway of SGLT2i related to these effects and to what extent it depends on the neural system are not fully understood. The evidence of how SGLT-2i interacts with the nervous system is worth exploring. Therefore, in this review, we will illustrate the potential neurological processes by which SGLT2i improves IR in skeletal muscle, liver, adipose tissue, and other insulin-target organs via the CNS and sympathetic nervous system/parasympathetic nervous system (SNS/PNS).

The Mechanism of Sodium-Glucose Cotransporter-2 Inhibitors in Reducing Uric Acid in Type 2 Diabetes Mellitus.

Hyperuricemia is a common comorbidity in patients with type 2 diabetes mellitus (T2DM), as insulin resistance (IR) or hyperinsulinemia is associated with higher serum uric acid (SUA) levels due to decreased uric acid (UA) secretion, and SUA vice versa is an important risk factor that promotes the occurrence and progression of T2DM and its complications. Growing evidence suggests that sodium-glucose cotransporter 2 inhibitors (SGLT-2i), a novel anti-diabetic drug initially developed to treat T2DM, may exert favorable effects in reducing SUA. Currently, one of the possible mechanisms is that SGLT2i increases urinary glucose excretion, probably inhibiting glucose transport 9 (GLUT9)-mediated uric acid reabsorption in the collecting duct, resulting in increased uric acid excretion in exchange for glucose reabsorption. Regardless of this possible mechanism, the underlying comprehensive mechanisms remain poorly elucidated. Therefore, in the present review, a variety of other potential mechanisms will be covered to identify the therapeutic role of SGLT-2i in hyperuricemia.

Relationship Between Sporadic Renal Cysts and Renal Function Detected by Isotope Renography in Type 2 Diabetes.

Purpose: This study aimed to reveal the relationship between the volume of sporadic renal cysts and renal function in patients with type 2 diabetes (T2D). Materials and Methods: One hundred and seventy-one patients that underwent renal imaging and other routine examinations at the Shanghai Pudong Hospital were included in this study. The Gates' method of glomerular filtration rate (GFR) was measured by 99mTc-DTPA renal dynamic imaging in addition to the eGFR, calculated by the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). Results: Our results showed that BMI, total iGFR, and eGFR showed significant differences between patients with T2D with or without SRC (p < 0.05). Spearman correlation analysis showed that cyst volume was positively correlated with Scr and gender but not iGFR (p > 0.05). The total iGFR positively correlated with eGFR (r = 0.83, p < 0.0001) and negatively with Scr (r = -0.78, p < 0.0001), age (r = -0.43, p < 0.0001), duration of T2D (r = -0.25, p = 0.001), and BMI (r = -0.21, p = 0.006) but not gender (r = -0.03, p = 0.668). The multilinear regression model revealed that gender (ß = 0.346, p < 0.001), iGFR (ß = -0.705, p < 0.001), and serum uric acid (ß = 0.195, p = 0.032) were independent predictors of Scr. Moreover, we observed a significant increase in Scr in males (p < 0.05). Finally, we found that the split kidney function reflected by iGFR and related parameters such as time to peak (PTT) and half time of excretion (excrete t1/2) did not mutually distinguish from each other significantly whether they are measured in patients with renal cysts or in those without renal cysts (p > 0.05). Conclusion: Our preliminary results suggest that in T2D, SRCs may be a renal complication of diabetic nephropathy. Although we found that the patients with renal cysts may display reduced iGFR, the volume of simple cysts seems not to exacerbate renal insufficiency. Isotope renography is a useful tool to evaluate the split kidney functions in diabetic patients who acquire single-side cysts.

Characterization of non-stenotic plaques in intracranial arteries with multi-contrast, multi-planar vessel wall image analysis.

OBJECTIVES: Non-stenotic plaques have been observed in intracranial arteries but are less understood compared to those in coronary and carotid arteries. We sought to compare plaque distribution and morphology between stenotic and non-stenotic intracranial plaques with MR vessel wall imaging (VWI) and quantitative image analysis. MATERIALS AND METHODS: Twenty-four patients with intracranial arterial stenosis or luminal irregularity on clinical imaging were scanned with a multi-contrast VWI protocol. Plaques were detected as focal wall thickening on co-registered multiplanar reformats of multi-contrast VWI, with assessment of the location and morphology. TOF-MRA was independently reviewed for any appreciable stenosis using the WAISD criteria. RESULTS: Across 504 arterial segments, a total of 80 plaques were detected, including 23 (29%) with stenosis on TOF-MRA, 56 (70%) without, and 1 (1%) not covered by TOF-MRA. Plaques involving the ICA were more likely to be non-stenotic than those involving other segments (80% versus 55%, p = 0.030) whereas the basilar artery (40%) and PCA (33%) had the lowest proportions of non-stenotic plaques. Maximum wall thickness, indicative of plaque burden, correlated poorly with degree of stenosis (p = 0.10) and overlapped substantially between stenotic and non-stenotic plaques (1.9 [1.5, 2.4] versus 2.0 [1.5, 2.2] mm, p = 0.074). CONCLUSIONS: Intracranial plaques without appreciable stenosis on TOF-MRA represent a large proportion of lesions throughout arterial segments but disproportionately affect the ICA. Morphological characterization of plaques with and without stenosis shows that luminal stenosis is a poor indicator of the underlying burden of intracranial atherosclerosis.

Multi-Planar, Multi-Contrast and Multi-Time Point Analysis Tool (MOCHA) for Intracranial Vessel Wall Characterization.

BACKGROUND: Three-dimensional (3D) intracranial vessel wall (IVW) magnetic resonance imaging can reliably image intracranial atherosclerotic disease (ICAD). However, an integrated, streamlined, and optimized workflow for IVW analysis to provide qualitative and quantitative measurements is lacking. PURPOSE: To propose and evaluate an image analysis pipeline (MOCHA) that can register multicontrast and multitime point 3D IVW for multiplanar review and quantitative plaque characterization. STUDY TYPE: Retrospective. POPULATION: A total of 11 subjects with ICAD (68 ± 10 years old, 6 males). FIELD STRENGTH/SEQUENCE: A 3.0 T, 3D time-of-flight gradient echo sequence and T1- and proton density-weighted fast spin echo sequences. ASSESSMENT: Each participant underwent two IVW sessions within 2 weeks. Scan and rescan IVW images were preprocessed using MOCHA. The presence of atherosclerotic lesions was identified in different intracranial arterial segments by two readers (GC and JS, 12 years of vascular MR imaging experience each) following an established review protocol to reach consensus on each of the reviews. For all locations with identified plaques, plaque length, lumen and vessel wall areas, maximum and mean wall thickness values, normalized wall index and contrast enhancement ratio were measured. STATISTICAL TESTS: Percent agreement and Cohen's κ were used to test scan-rescan reproducibility of detecting plaques using MOCHA. Intraclass correlation coefficient (ICC) and Bland-Altman analysis were used to evaluate scan-rescan reproducibility for plaque morphologic and enhancement measurements. RESULTS: In 150 paired intracranial vessel segments, the overall agreement in plaque detection was 92.7% (κ = 0.822). The ICCs (all ICCs > 0.90) and Bland-Altman plots (no bias observed) indicated excellent scan-rescan reproducibility for all morphologic and enhancement measurements. DATA CONCLUSION: Findings from this study demonstrate that MOCHA provides high scan-rescan reproducibility for identification and quantification of atherosclerosis along multiple intracranial arterial segments and highlight its potential use in characterizing plaque composition and monitoring plaque development. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Low TSH Levels Within Euthyroid Range Could Play a Negative Role on Bone Mineral Density in Postmenopausal Women with Type 2 Diabetes.

OBJECTIVE: We aimed to evaluate the relationship between thyroid-stimulating hormone (TSH) and bone mineral density (BMD) in euthyroid type 2 diabetes (T2D). METHODS: This retrospective analysis enrolled 439 T2D patients with normal thyroid function, including 226 males and 213 females. All the female patients were postmenopausal. Serum glycosylated hemoglobin A1c (HbA1c), TSH, free triiodothyronine (FT3), and free thyroxine (FT4) concentrations were analyzed. BMD of the lumbar spine (L1-L4), femoral neck, and hip joint was determined using dual-energy X-ray absorptiometry. RESULTS: The patients were grouped based on tri-sectional quantiles of the TSH levels: 0.55~1.70mIU/L (Group 1), 1.71~2.58mIU/L (Group 2), and 2.59~4.74mIU/L (Group 3). Our data showed that, in male patients, no difference in BMD was identified among groups. In postmenopausal women, unlike at the lumbar spine (P = 0.459), the mean BMD at the femoral neck (P = 0.014) and hip joint (P = 0.014) had a statistical difference among groups and increased with TSH level. In addition, our analysis demonstrated that TSH levels shown no correlation with BMD at all sites in males. However, in females, BMD at the femoral neck (r = 0.156, P = 0.023) and hip joint (r = 0.172, P = 0.012) had a positive correlation with TSH levels. After adjusting for age and BMI, multiple regression analysis showed that TSH levels influenced BMD at the femoral neck (ß = 0.188, P = 0.001) and hip joint (ß = 0.204, P = 0.001) in female patients. CONCLUSION: In summary, our data demonstrates that low TSH levels are associated with decreased BMD at the femoral neck and hip joint in postmenopausal T2D women with euthyroidism.

Domain adaptive and fully automated carotid artery atherosclerotic lesion detection using an artificial intelligence approach (LATTE) on 3D MRI.

PURPOSE: To develop and evaluate a domain adaptive and fully automated review workflow (lesion assessment through tracklet evaluation, LATTE) for assessment of atherosclerotic disease in 3D carotid MR vessel wall imaging (MR VWI). METHODS: VWI of 279 subjects with carotid atherosclerosis were used to develop LATTE, mainly convolutional neural network (CNN)-based domain adaptive lesion classification after image quality assessment and artery of interest localization. Heterogeneity in test sets from various sites usually causes inferior CNN performance. With our novel unsupervised domain adaptation (DA), LATTE was designed to accurately classify arteries into normal arteries and early and advanced lesions without additional annotations on new datasets. VWI of 271 subjects from four datasets (eight sites) with slightly different imaging parameters/signal patterns were collected to assess the effectiveness of DA of LATTE using the area under the receiver operating characteristic curve (AUC) on all lesions and advanced lesions before and after DA. RESULTS: LATTE had good performance with advanced/all lesion classification, with the AUC of >0.88/0.83, significant improvements from >0.82/0.80 if without DA. CONCLUSIONS: LATTE can locate target arteries and distinguish carotid atherosclerotic lesions with consistently improved performance with DA on new datasets. It may be useful for carotid atherosclerosis detection and assessment on various clinical sites.

Chronic kidney disease, atherosclerotic plaque characteristics on carotid magnetic resonance imaging, and cardiovascular outcomes.

BACKGROUND: It is unclear whether faster progression of atherosclerosis explains the higher risk of cardiovascular events in CKD. The objectives of this study were to 1. Characterize the associations of CKD with presence and morphology of atherosclerotic plaques on carotid magnetic resonance imaging (MRI) and 2. Examine the associations of baseline CKD and carotid atherosclerotic plaques with subsequent cardiovascular events. METHODS: In a subgroup (N = 465) of Systolic Blood Pressure Intervention Trial. (SPRINT) participants, we measured carotid plaque presence and morphology at baseline and after 30-months with MRI. We examined the associations of CKD (baseline eGFR < 60 ml/min/1.73m2) with progression of carotid plaques and the SPRINT cardiovascular endpoint. RESULTS: One hundred and ninety six (42%) participants had CKD. Baseline eGFR in the non-CKD and CKD subgroups were 77 ± 14 and 49 ± 8 ml/min/1.73 m2, respectively. Lipid rich necrotic-core plaque was present in 137 (29.5%) participants. In 323 participants with both baseline and follow-up MRI measurements of maximum wall thickness, CKD was not associated with progression of maximum wall thickness (OR 0.62, 95% CI 0.36 to 1.07, p = 0.082). In 96 participants with necrotic core plaque at baseline and with a valid follow-up MRI, CKD was associated with lower odds of progression of necrotic core plaque (OR 0.41, 95% CI 0.17 to 0.95, p = 0.039). There were 28 cardiovascular events over 1764 person-years of follow-up. In separate Cox models, necrotic core plaque (HR 2.59, 95% CI 1.15 to 5.85) but not plaque defined by maximum wall thickness or presence of a plaque component (HR 1.79, 95% CI 0.73 to 4.43) was associated with cardiovascular events. Independent of necrotic core plaque, CKD (HR 3.35, 95% CI 1.40 to 7.99) was associated with cardiovascular events. CONCLUSIONS: Presence of necrotic core in carotid plaque rather than the presence of plaque per se was associated with increased risk of cardiovascular events. We did not find CKD to be associated with faster progression of necrotic core plaques, although both were independently associated with cardiovascular events. Thus, CKD may contribute to cardiovascular disease principally via mechanisms other than atherosclerosis such as arterial media calcification or stiffening. TRIAL REGISTRATION: NCT01475747 , registered on November 21, 2011.

Dapagliflozin Activates Neurons in the Central Nervous System and Regulates Cardiovascular Activity by Inhibiting SGLT-2 in Mice.

PURPOSE: This study investigates the possible effect and central mechanism of novel antidiabetic medication sodium glucose transporter-2 (SGLT-2i) on the cardiovascular activity. MATERIAL AND METHODS: Thirty-four normal male C57BL/6 mice were randomly assigned to 2 groups to receive single Dapagliflozin (1.52mg/kg) dose via intragastric gavage or a comparable dose of saline. Glycemic level (BG), blood pressure (BP) and heart rate (HR) were measured 2 hours after administration of the respective treatments. Immunohistochemical tests were performed to determine the effect of SGLT-2i on neural localization of SGLT-2 and c-Fos, a neural activator. The distributional relationships of SGLT-2 and c-Fos were examined by immunofluorescence. RESULTS: Administration of SGLT-2i significantly decreased BP but did not affect the HR. There was no difference in BG between the two groups. Results showed that SGLT-2 was localized to specific regions involved in autonomic control. Expression of c-Fos was significantly higher in major critical nuclei in the aforementioned regions in groups treated with Dapagliflozin. CONCLUSION: This study demonstrates that SGLT-2 is expressed in CNS tissues involved in autonomic control and possibly influence cardiovascular function. Dapagliflozin influences central autonomic activity via unidentified pathways by inhibiting central or peripheral SGLT-2. These results provide a new concept that sympathetic inhibition by SGLT-2i can be mediated by central autonomic system, a mechanism that explains how SGLT-2i improves the cardiovascular function.

High-resolution MRI assessed carotid atherosclerotic plaque characteristics comparing men and women with elevated ApoB levels.

Previous studies demonstrated that men were more likely to have plaque rupture and are at greater risk for myocardial infarction and stroke than women. We evaluated differences in carotid plaque characteristics by MRI between men and women with mild-moderate atherosclerosis and elevated ApoB levels. One hundred eighty-two subjects (104 men and 78 women) with CAD or carotid stenosis (≥ 15% by ultrasound), ApoB ≥ 120 mg/dL and carotid MRI scan were included. Percent wall volume (%WV) was calculated as (wall volume/total vessel volume) × 100%. Three major plaque compositions, fibrous tissue (FT), calcification (CA) and lipid rich necrotic core (LRNC), were identified and quantified using published MRI criteria. Adventitial and plaque neovascularization as fractional plasma volume (Vp) and permeability as transfer constant (Ktrans) were analyzed using kinetic modeling. These characteristics were compared between men and women. Men, compared to women, were younger (54 ± 8 vs. 58 ± 8 years, p = 0.01), had higher rate of previous MI (46 vs. 26%, p = 0.005) but lower proportions of metabolic syndrome (37 vs. 59%, p = 0.003). After adjusting for between-gender differences, men were significantly more likely to have LRNC (OR 2.22, 95% CI 1.04-4.89, p = 0.04) and showed significantly larger %LRNC than women (diff = 4.3%, 95% CI 1.6-6.9%, p = 0.002), while %WV, FT, and CA were similar between men and women. There were no statistically significant differences in adventitial and plaque Vp or Ktrans. Men were significantly more likely to have LRNC and had larger LRNC than women. However, men and women showed relatively similar levels of adventitial and plaque neovascularization and permeability.Trial registration: NCT00715273 at ClinicalTrials.gov. Registered 15 July 2008, retrospectively registered.

Evaluation of 3D multi-contrast carotid vessel wall MRI: a comparative study.

BACKGROUND: Conventional reference multi-contrast black-blood (BB) MRI can be used for measuring luminal stenosis severity and plaque components, and its performance has been validated by intra- and inter-reader reproducibility test and histology. Recently, a set of 3D multi-contrast BB sequences have been developed, but its accuracy and reliability have not been well investigated. In this study, we evaluated the performance of 3D multi-contrast MRI (3D-MERGE, T2-VISTA, and SNAP) by comparing it with reference multi-contrast vessel wall MRI and assessing the inter-reader reproducibility. METHODS: In total, 27 patients were recruited in this study. Twenty-six participants underwent reference and 3D multi-contrast imaging in a 3.0T MR scanner. One participant underwent carotid endarterectomy (CEA) after 3D MR imaging. Two trained reviewers interpreted reference and 3D datasets. Lumen area (LA), wall area (WA), normalized wall index (NWI), maximum wall thickness (MaxWT), and mean wall thickness (MWT) were measured, and the presence of lipid-rich necrotic core (LRNC), intra-plaque hemorrhage (IPH) and calcification (CA) were identified. Inter-reader reproducibility of 3D interpretation was assessed. RESULTS: 3D imaging provided comparable measurements with reference imaging in LA (43.81±25.74 vs. 43.35±24.66 mm2) and MaxWT (1.65±1.33 vs. 1.62±1.10 mm), with a lower NWI (0.40±0.15 vs. 0.43±0.11), WA (29.40±21.92 vs. 30.64±16.17 mm2) and MWT (1.09±0.69 vs. 1.14±0.47), and showed good agreement for identification of LRNC (κ=0.66, 95% CI: 0.30-1.00) and CA (κ=0.69, 95% CI: 0.42-0.97), and excellent agreement for IPH (κ=1.00, 95% CI: 1.00-1.00). Inter-reader agreement of 3D analysis was good (LRNC, κ=0.87, 95% CI: 0.61-1.00; CA, κ=0.66, 95% CI: 0.36-0.96; IPH, κ=1.00, 95% CI: 1.00-1.00). CONCLUSIONS: 3D multi-contrast vessel wall imaging provides comparable performance in morphological measurements and identification of carotid plaque components as reference multi-contrast MRI, with good inter-reader reproducibility.

Imaging of Carotid Plaque Neovascularization by Contrast-Enhanced Ultrasound and Dynamic Contrast-Enhanced Magnetic Resonance Imaging.

BACKGROUND: Carotid plaque neovascularization (vasa vasorum [VV]) may be useful for detecting high-risk atherosclerotic plaques. Contrast-enhanced ultrasound (CEUS) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) are 2 commonly used techniques for imaging VV of the carotid plaque, yet the relationship between their measurements remains unknown. OBJECTIVES: We aimed to blindly evaluate the correlation between CEUS and DCE-MRI in measuring carotid plaque VV. METHODS: We recruited subjects with asymptomatic carotid stenosis (≥50%). VV was graded by CEUS, based on richness of contrast signal, according to 3 different methods named CEUS_A, CEUS_B and CEUS_C on different point scales (the higher the values, the higher the estimated VV). A 3.0 T MRI scanner was used for VV quantification by DCE-MRI using gadolinium contrast kinetic modelling for computing the fractional plasma volume (vp) and transfer constant (Ktrans). RESULTS: The analysis included 30 patients. A significant correlation between CEUS and DCE-MRI findings was observed when CEUS_C was used for neovessel grading and DCE-MRI was used to determine adventitial (r = 0.460, p = 0.010) and plaque (r = 0.374, p = 0.042) Ktrans values. CEUS_B (r = 0.416, p = 0.022) and CEUS_C (r = 0.443, p = 0.014) grading showed a significant correlation with regard to the maximal Ktrans. CONCLUSIONS: We found a positive but weak correlation and a moderate diagnostic agreement between neovessels as visually graded by CEUS and adventitial neovessels assessed by DCE-MRI Ktrans in carotid atherosclerosis. These findings may help in understanding how VV density, flow, and permeability influence in vivo measurements by CEUS and DCE-MRI as well as in selecting the most appropriate variables and imaging method in future research and potentially in clinical settings. Further confirmative studies are necessary to confirm our results.

Deep morphology aided diagnosis network for segmentation of carotid artery vessel wall and diagnosis of carotid atherosclerosis on black-blood vessel wall MRI.

PURPOSE: Early detection of carotid atherosclerosis on the vessel wall (VW) magnetic resonance imaging (MRI) (VW-MRI) images can prevent the progression of cardiovascular disease. However, the manual inspection process of the VW-MRI images is cumbersome and has low reproducibility. Therefore in this paper, by using the convolutional neural networks (CNNs), we develop a deep morphology aided diagnosis (DeepMAD) network for automated segmentation of the VW of carotid artery and for automated diagnosis of the carotid atherosclerosis with the black-blood (BB) VW-MRI (i.e., the T1-weighted MRI) in a slice-by-slice manner. METHODS: The proposed DeepMAD network consists of a segmentation subnetwork and a diagnosis subnetwork for performing the segmentation and diagnosis tasks on the BB-VW-MRI images, where the manual labeled lumen area, the manual labeled outer wall area and the manual labeled lesion Types based on the modified American Heart Association (AHA) criteria are used as the ground-truth. Specifically, a deep U-shape CNN with a weighted fusion layer is designed as the segmentation subnetwork, where the lumen area and the outer wall area can be simultaneously segmented under the supervision of the triple Dice loss to provide the vessel wall map as morphological information. Then, the image stream from the BB-VWMRI image and the morphology stream from the obtained vessel wall map are extracted from two deep CNNs and combined to obtain the diagnosis results of atherosclerosis in the diagnosis subnetwork. In addition, the triple input set is formed by three carotid regions of interest (ROIs) from three consecutive slices of the MRI sequence and input to the DeepMAD network, where the first and last slices used as additional adjacent slices to provide 2.5D spatial information along the carotid artery centerline for the intermediate slice, which is the target slice for segmentation and diagnosis in the study. RESULTS: Compared to other existing methods, the DeepMAD network can achieve promising segmentation performances (0.9594 Dice for the lumen and 0.9657 Dice for the outer wall) and better diagnosis Accuracy of the carotid atherosclerosis (0.9503 AUC and 0.8916 Accuracy) in the test dataset (including invisible subjects) from same source as the training dataset. In addition, the trained DeepMAD model can be successfully transferred to another test dataset for segmentation and diagnosis tasks with remarkable performance (0.9475 Dice for the lumen and 0.9542 Dice for the outer wall, 0. 9227 AUC and 0.8679 Accuracy for diagnosis). CONCLUSIONS: Even without the intervention of reviewers required for previous works, the proposed DeepMAD network automatically segments the lumen and the outer wall together and diagnoses the carotid atherosclerosis with high performances. The DeepMAD network can be used in clinical trials to help radiologists get rid of tedious reading tasks, such as screening review to separate the normal carotid from the atherosclerotic arteries and outlining the vessel wall contours.

Interoperator Reproducibility of Carotid Elastography for Identification of Vulnerable Atherosclerotic Plaques.

Ultrasound-based carotid elastography has been developed to evaluate the vulnerability of carotid atherosclerotic plaques. The aim of this study was to investigate the in vivo interoperator reproducibility of carotid elastography for the identification of vulnerable plaques, with high-resolution magnetic resonance imaging (MRI) as reference. Ultrasound radio-frequency data of 45 carotid arteries (including 53 plaques) from 32 volunteers were acquired separately by two experienced operators in the longitudinal view and then were used to estimate the interframe axial strain rate (ASR) with a two-step optical flow method. The maximum 99th percentile of absolute ASR of all plaques in a carotid artery was used as the elastographic index. MRI scanning was also performed on each volunteer to identify the vulnerable plaque. The results showed no systematic bias in the Bland-Altman plot and an intraclass correlation coefficient of 0.66 between the two operators. In addition, no statistical significance was found between the receiver operating characteristic (ROC) curves from the two operators ( ), and their areas under the ROC curves were 0.83 and 0.77, respectively. Using the mean measurements of the two operators as the classification criterion, a sensitivity of 71.4%, a specificity of 87.1%, and an accuracy of 82.2% were obtained with a cutoff value of 1.37 [Formula: see text]. This study validates the interoperator reproducibility of ultrasound-based carotid elastography for identifying vulnerable carotid plaques.

Identification of carotid lipid-rich necrotic core and calcification by 3D magnetization-prepared rapid acquisition gradient-echo imaging.

BACKGROUND AND PURPOSE: This study sought to investigate the feasibility of three-dimensional MPRAGE in identifying the lipid-rich necrotic core (LRNC) and calcification (CA) of carotid atherosclerotic plaques. MATERIALS AND METHODS: Twelve patients (mean age 68.4 ±â€¯11.8 years; 7 males) with carotid atherosclerotic plaques on ultrasound were included and underwent multicontrast magnetic resonance (MR) vessel wall imaging. The contrast enhanced T1W (CE-T1W) images were considered as reference for identifying LRNC. The signal intensity of LRNC, CA, sterno-cleidomastoid muscle and fibrous tissue (FT) was measured on CE-T1W, T1W, T2W, and MPRAGE images, respectively. The relative signal intensity (rSI) of LRNC and CA against muscle or FT was compared among four sequences. Area under the curve (AUC) of rSIs of LRNC, CA and FT against muscle on MPRAGE, T1W and T2W images in discriminating the LRNC or CA from FT and the other plaque component was calculated. RESULTS: Of 352 slices, 88 (25.0%) had LRNC, 31 (8.8%) had CA, 14 (4.0%) had both LRNC and CA, and 247 (70.2%) had no components. Among four imaging sequences, MPRAGE images showed the lowest rSI of LRNC (0.34 ±â€¯0.18) and CA (0.20 ±â€¯0.16) against muscle, followed by T1W (0.48 ±â€¯0.18 and 0.33 ±â€¯0.21), CE-T1W (0.58 ±â€¯0.23 and 0.40 ±â€¯0.21) and T2W (0.71 ±â€¯0.47 and 0.43 ±â€¯0.40) images. In addition, the MPRAGE images showed the lowest rSI of LRNC (0.57 ±â€¯0.26) and CA (0.33 ±â€¯0.23) against FT. MPRAGE showed greater AUC than T2W and T1W in discriminating the LRNC (0.827 vs. 0.703 vs. 0.635) and CA (0.917 vs. 0.838 vs. 0.825). CONCLUSION: MPRAGE sequence might be a potential non-contrast enhanced imaging tool for identification of carotid LRNC and CA.

Femoral artery plaque characteristics, lower extremity collaterals, and mobility loss in peripheral artery disease.

Little is known about the prognostic significance of specific characteristics of magnetic resonance imaging (MRI) measured plaque in the superficial femoral artery (SFA). Associations of MRI-measured plaque quantity, lumen area, and plaque composition in the SFA with subsequent mobility loss were studied in people with lower extremity peripheral artery disease (PAD). Participants with an ankle-brachial index (ABI) < 1.00 were identified from Chicago medical centers and underwent direct visualization of atherosclerotic plaque in the SFA using MRI. Participants were followed annually for up to 4 years. Mobility loss was defined as becoming unable to walk up and down a flight of stairs or walk one-quarter of a mile without assistance among participants without mobility impairment at baseline. Analyses adjusted for age, sex, race, comorbidities, ABI, physical activity, and other confounders. Of 308 PAD participants without baseline mobility impairment, 100 (32.5%) developed mobility loss during follow-up. Compared to the lowest mean plaque area tertile at baseline, participants in the highest (worst) plaque area tertile had a higher rate of mobility loss (hazard ratio (HR) = 2.08, 95% confidence interval (CI) = 1.14-3.79, p = 0.018). Compared to the highest mean lumen area tertile, the smallest (worst) mean lumen area tertile was associated with greater mobility loss (HR = 2.18, 95% CI = 1.20-3.96, p = 0.011). Neither lipid rich necrotic core nor calcium in the SFA were associated with mobility loss. In conclusion, greater plaque quantity and smaller lumen area in the proximal SFA, but not lipid rich necrotic core or calcium, were associated with higher mobility loss in people with PAD.

Prevalence and Characteristics of Carotid Artery High-Risk Atherosclerotic Plaques in Chinese Patients With Cerebrovascular Symptoms: A Chinese Atherosclerosis Risk Evaluation II Study.

BACKGROUND: Carotid atherosclerotic plaque rupture is an important source of ischemic stroke. However, the prevalence of high-risk plaque (HRP) defined as plaques with luminal surface disruption, a lipid-rich necrotic core occupying >40% of the wall, or intraplaque hemorrhage in Chinese population remains unclear. This study uses carotid magnetic resonance imaging (CMRI) to investigate HRP prevalence in carotid arteries of Chinese patients with cerebrovascular symptoms. METHODS AND RESULTS: Patients with cerebral ischemic symptoms in the anterior circulation within 2 weeks and carotid plaque determined by ultrasound were recruited and underwent CMRI. The HRP features were identified and compared between symptomatic and asymptomatic arteries. Receiver-operating-characteristic analysis was used to calculate area-under-the-curve (AUC) of stenosis and maximum wall thickness for discriminating presence of HRP. In 1047 recruited subjects, HRP detected by CMRI was nearly 1.5 times more prevalent than severe stenosis (≥50%) in this cohort (28% versus 19%, P<0.0001). Approximately two thirds of HRPs were found in arteries with <50% stenosis. The prevalence of HRP in symptomatic carotid arteries was significantly higher than that of the contralateral asymptomatic carotid arteries (23.0% versus 16.4%, P=0.001). Maximum wall thickness was found to be a stronger discriminator than stenosis for HRP (AUC: 0.93 versus 0.81, P<0.0001). CONCLUSIONS: There are significantly more high-risk carotid plaques than carotid arteries with ≥50% stenosis in symptomatic Chinese patients. A substantial number of HRPs were found in arteries with lower grade stenosis and maximum wall thickness was a stronger indicator for HRP than luminal stenosis. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02017756.

Plaque Composition in the Proximal Superficial Femoral Artery and Peripheral Artery Disease Events.

OBJECTIVES: The aim of this study was to describe associations of the presence of lipid-rich necrotic core (LRNC) in the proximal superficial femoral artery (SFA) with lower extremity peripheral artery disease (PAD) event rates and systemic cardiovascular event rates. BACKGROUND: LRNC in the coronary and carotid arteries is associated with adverse outcomes but has not been studied previously in lower extremity arteries. METHODS: Participants with ankle-brachial index (ABI) values <1.00 were identified from Chicago medical centers and followed annually. Magnetic resonance imaging was used to characterize SFA atherosclerotic plaque at baseline. Medical records for hospitalizations and procedures after baseline were adjudicated for lower extremity revascularization, amputation, and critical limb ischemia and also for new coronary events, ischemic stroke, and mortality. RESULTS: Of 254 participants with PAD, 62 (24%) had LRNC and 149 (59%) had calcium in the SFA at baseline. Cox regression analyses were adjusted for age, sex, race, comorbidities, baseline ABI, and other confounders. SFA LRNC was associated with an increased incidence of the combined outcome of lower extremity amputation, critical limb ischemia, ABI decline >0.15, and revascularization at 47-month follow-up (hazard ratio: 2.18; 95% confidence interval: 1.27 to 3.75; p = 0.005). The association of SFA LRNC with PAD events was maintained even when this combined outcome excluded lower extremity revascularization (hazard ratio: 2.58; 95% confidence interval: 1.25 to 5.33; p = 0.01). LRNC in the SFA was not associated with all-cause mortality, acute coronary events, or stroke. CONCLUSIONS: Among patients with PAD, LRNC in the SFA was associated with higher rates of clinical PAD events, and this association was independent of ABI. Further study is needed to determine whether interventions that reduce SFA LRNC prevent PAD events.