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.

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.

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.

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.

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.

Blood Pressure Is a Major Modifiable Risk Factor Implicated in Pathogenesis of Intraplaque Hemorrhage: An In Vivo Magnetic Resonance Imaging Study.

OBJECTIVE: Effective prevention and management strategies of intraplaque hemorrhage (IPH) remain elusive because of our limited knowledge regarding its contributing factors. This hypothesis-generating study aimed to investigate associations between cardiovascular risk factors and IPH for improved understanding of the pathogenesis of IPH. APPROACH AND RESULTS: Asymptomatic subjects with 16% to 79% stenosis on ultrasound underwent carotid magnetic resonance imaging using a large-coverage, 3-dimensional magnetic resonance imaging protocol. Individual plaques (maximum thickness >1.5 mm) in bilateral carotid arteries were identified, and presence of IPH was determined. From 80 subjects, 176 de novo plaques were measured, of which 38 (21.6%) contained IPH. Blood pressure (BP), primarily low diastolic BP, was associated with IPH in multivariate analysis adjusted for age, sex, and plaque size (odds ratio with 95% confidence interval per 10-mm Hg increase: 0.51 [0.30-0.88]), which was little changed after adjusting for antihypertensive use and systemic atherosclerosis. Antiplatelet use was associated with IPH in age and sex-adjusted models (P=0.018), for which a trend remained after considering plaque size and past medical history (odds ratio for aspirin alone versus none: 3.1 [0.66-14.8]; odds ratio for clopidogrel or dual therapy versus none: 5.3 [0.80-35.0]; P=0.083). CONCLUSIONS: Low diastolic BP was independently associated with IPH, which was not attributed to treatment difference or BP changes from systemic atherosclerosis. Hemodynamic changes from lowering diastolic BP may be the pathophysiological link. Prospective serial studies are needed to assess whether BP and antiplatelet use are associated with the development of new or repeated IPH.

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.

Identification of early atherosclerotic lesions in carotid arteries with quantitative characteristics measured by 3D MRI.

PURPOSE: To evaluate the usefulness of quantitative characteristics of morphology and signal intensity of arterial wall measured by 3D multicontrast magnetic resonance vessel wall imaging (MRVWI) in identification of carotid early atherosclerosis (CEAS). MATERIALS AND METHODS: In all, 61 older subjects (mean age 71.8 ± 5.6 years old; 25 males) without cardiovascular symptoms in the last 6 months were recruited. The carotid arteries without advanced plaque features on 3.0T MRI were included for analysis. Ultrasound imaging was used as a reference to identify CEAS. The morphological parameters including lumen area (LA), wall area (WA), wall thickness (WT), and normalized wall index (NWI = WA/[WA+LA] × 100%) and the signal intensity on 3.0T MR T2 -weighted images (T2 SI) of the carotid arterial wall were measured. Three regression models were built to identify CEAS with the following parameters: Model 1 with both morphological and T2 SI parameters; Model 2 with T2 SI parameters; and Model 3 with morphological parameters. All models were adjusted for age and sex. Area under the curve (AUC) was calculated to validate models. RESULTS: Of the 86 carotid arteries without advanced plaques, 47 (54.7%) were found to have early plaques determined by ultrasound. Among three regression models, Model 1 showed the highest AUC values in identifying CEAS (left: AUC = 0.856, P < 0.001; right: AUC = 0.867, P < 0.001), followed by Model 2 (left: AUC = 0.843, P < 0.001; right: AUC = 0.798, P = 0.001), and Model 3 (left: AUC = 0.790, P = 0.002; right: AUC = 0.806, P < 0.001). CONCLUSION: The combination of morphology and normalized T2 SI of arterial wall measured by MRVWI is more effective than each characteristic alone in identification of CEAS. J. Magn. Reson. Imaging 2016;44:1270-1276.

Semi-automatic carotid intraplaque hemorrhage detection and quantification on Magnetization-Prepared Rapid Acquisition Gradient-Echo (MP-RAGE) with optimized threshold selection.

BACKGROUND: Intraplaque hemorrhage (IPH) is associated with atherosclerosis progression and subsequent cardiovascular events. We sought to develop a semi-automatic method with an optimized threshold for carotid IPH detection and quantification on MP-RAGE images using matched histology as the gold standard. METHODS: Fourteen patients scheduled for carotid endarterectomy underwent 3D MP-RAGE cardiovascular magnetic resonance (CMR) preoperatively. Presence and area of IPH were recorded using histology. Presence and area of IPH were also recorded on CMR based on intensity thresholding using three references for intensity normalization: the sternocleidomastoid muscle (SCM), the adjacent muscle and the automatically generated local median value. The optimized intensity thresholds were obtained by maximizing the Youden's index for IPH detection. Using leave-one-out cross validation, the sensitivity and specificity for IPH detection based on our proposed semi-automatic method and the agreement with histology on IPH area quantification were evaluated. RESULTS: The optimized intensity thresholds for IPH detection were 1.0 times the SCM intensity, 1.6 times the adjacent muscle intensity and 2.2 times the median intensity. Using the semi-automatic method with the optimized intensity threshold, the following IPH detection and quantification performance was obtained: sensitivities up to 59, 68 and 80 %; specificities up to 85, 74 and 79 %; Pearson's correlation coefficients (IPH area measurement) up to 0.76, 0.93 and 0.90, respectively, using SCM, the adjacent muscle and the local median value for intensity normalization, after heavily calcified and small IPH were excluded. CONCLUSIONS: A semi-automatic method with good performance on IPH detection and quantification can be obtained in MP-RAGE CMR, using an optimized intensity threshold comparing to the adjacent muscle. The automatically generated reference of local median value provides comparable performance and may be particularly useful for developing automatic classifiers. Use of the SCM intensity as reference is not recommended without coil sensitivity correction when surface coils are used.

Dual energy computed tomography quantification of carotid plaques calcification: comparison between monochromatic and polychromatic energies with pathology correlation.

PURPOSE: We compared carotid plaque calcification detection sensitivity and apparent cross-sectional area on CT as a function of CT beam energy using conventional CT techniques and virtual mono-energetic CT images generated from dual-energy acquisitions. METHODS & MATERIALS: Five ex-vivo carotid endarterectomy (CEA) specimens were imaged with dual-energy computed tomography. Virtual monochromatic spectrum (VMS) CT images were reconstructed at energies between 40-140 keV. The same specimens were imaged using conventional polyenergetic spectrum (PS) CT with peak beam energies 80, 100, 120, and 140 kVp. The histological calcium areas on each corresponding CEA specimen were traced manually on digitized images of Toluidine-Blue/Basic-Fuchsin stained plastic sections. RESULTS: 40 keV VMS CT images provided high detection sensitivity (97 %) similar to conventional PS CT images (~96 %). The calcification size measured on CT decreased systematically with increasing CT beam energy; the rate of change was larger for the VMS images than for PS images. CONCLUSION: From a single dual-energy CT, multiple VMS-CT images can be generated, yielding equivalent detection sensitivity and size correlations as conventional PS-CT in CEA calcification imaging. VMS-CT at 80-100 keV provided the most accurate estimates of calcification size, as compared to histology, but detection sensitivity was reduced for smaller calcifications on these images. KEY POINTS: • Calcifications depicted at 80-100 keV were most similar to the histology standard. • Conventional polychromatic images demonstrated excellent correlation with plaque size at pathology. • Conventional polychromatic images systematically overestimate plaque size. • Plaque calcifications can be missed on high energy monochromatic images.

Collateral vessel number, plaque burden, and functional decline in peripheral artery disease.

Associations of collateral vessels and lower extremity plaque with functional decline are unknown. Among people with peripheral artery disease (PAD), we determined whether greater superficial femoral artery (SFA) plaque burden combined with fewer lower extremity collateral vessels was associated with faster functional decline, compared to less plaque and/or more numerous collateral vessels. A total of 226 participants with ankle-brachial index (ABI) <1.00 underwent magnetic resonance imaging of lower extremity collateral vessels and cross-sectional imaging of the proximal SFA. Participants were categorized as follows: Group 1 (best), maximum plaque area < median and collateral vessel number ≥6 (median); Group 2, maximum plaque area < median and collateral vessel number <6; Group 3, maximum plaque area > median and collateral vessel number ≥6; Group 4 (worst), maximum plaque area > median and collateral vessel number <6. Functional measures were performed at baseline and annually for 2 years. Analyses adjust for age, sex, race, comorbidities, and other confounders. Annual changes in usual-paced walking velocity were: Group 1, +0.01 m/s; Group 2, -0.02 m/s; Group 3, -0.01 m/s; Group 4, -0.05 m/s (p-trend=0.008). Group 4 had greater decline than Group 1 (p<0.001), Group 2 (p=0.029), and Group 3 (p=0.010). Similar trends were observed for fastest-paced 4-meter walking velocity (p-trend=0.018). Results were not substantially changed when analyses were repeated with additional adjustment for ABI. However, there were no associations of SFA plaque burden and collateral vessel number with decline in 6-minute walk. In summary, a larger SFA plaque burden combined with fewer collateral vessels is associated with a faster decline in usual and fastest-paced walking velocity in PAD.

Subclinical carotid atherosclerosis: short-term natural history of lipid-rich necrotic core--a multicenter study with MR imaging.

PURPOSE: To use magnetic resonance (MR) imaging to examine the short-term (6 months) natural history of the lipid-rich necrotic core (LRNC) in carotid artery plaques by examining the placebo group of a multicenter clinical trial. MATERIALS AND METHODS: Study procedures and consent forms were approved by the institutional review board for this HIPAA-compliant study. Written informed consent was obtained for all enrolled subjects. Subjects in the placebo group of a multicenter clinical trial who showed LRNC at screening MR imaging had a follow-up MR imaging examination after 6 months. Lumen and wall volumes and LRNC volume and percentage were measured on images from both examinations by readers who were blinded to the time sequence. Plaque progression was calculated as annualized change in common coverage by using the carotid artery bifurcation as a landmark. Associations of clinical and imaging variables with LRNC progression were examined by using linear regression analysis. RESULTS: Fifty-nine of 73 (81%) subjects completed the study, with a mean interval ± standard deviation of 6.9 months ± 1.0. The mean progression rates per year ± standard deviation of LRNC volume and percentage were -5.2 mm(3) ± 34.3 (P = .249) and -1.74% ± 6.27% (P = .038), respectively. Of the clinical and imaging variables examined, presence of intraplaque hemorrhage (IPH) was significantly associated with LRNC progression (P = .001). Plaques with IPH had increased LRNC volume per year (62.9 mm(3) ± 46.2 vs -8.8 mm(3) ± 29.9, P < .001) and percentage per year (3.67% ± 1.85% vs -2.03% ± 6.30%, P = .126) compared with those without IPH. Spearman correlation analysis showed that change in LRNC positively correlated with change in wall volume (ρ = 0.60, P < .001), but not with change in lumen volume (ρ = -0.17, P = .201). CONCLUSION: Serial MR imaging of the carotid artery allowed observation of changes in LRNC over a short follow-up period and demonstrated the complexity of plaque progression patterns related to tissue composition. LRNC progression may be influenced not only by clinical characteristics, but also and to a large extent by plaque characteristics such as IPH.

Changes in measured size of atherosclerotic plaque calcifications in dual-energy CT of ex vivo carotid endarterectomy specimens: effect of monochromatic keV image reconstructions.

OBJECTIVE: The aim of this study was to compare the size of the calcifications measured on the different keV images to a histological standard. METHODS: Five ex vivo carotid endarterectomy (CEA) specimens were imaged with a dual-energy CT. CT images were reconstructed at different monochromatic spectral energies (40, 60, 77, 80, 100, 120, 140 keV). Cross-sectional area of the plaque calcifications present on each CT image was measured. The histological calcium areas on each corresponding CEA specimen were traced manually on digitised images of Toluidine Blue/Basic Fuchsin stained plastic sections. The CT images and corresponding histology sections were matched. The CT-derived calcium areas on each keV image were compared to the calcified area measurements by histology. RESULTS: A total of 107 histology sections were matched to corresponding CT images. The average calcified area per section by histology was 7.6 ± 7 mm(2) (range 0-26.4 mm(2)). There was no significant difference between the calcified areas measured by histology and those measured on CT-virtual monochromatic spectral (VMS) reconstructed images at 77 keV (P = 0.08), 80 keV (P = 0.20) and 100 keV (P = 0.14). CONCLUSIONS: Calcium area measured on the 80 keV image set was most comparable to the amount of calcium measured by histology.

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.

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).

Quantitative evaluation of high intensity signal on MIP images of carotid atherosclerotic plaques from routine TOF-MRA reveals elevated volumes of intraplaque hemorrhage and lipid rich necrotic core.

BACKGROUND: Carotid intraplaque hemorrhage (IPH) and lipid rich necrotic core (LRNC) have been associated with accelerated plaque growth, luminal narrowing, future surface disruption and development of symptomatic events. The aim of this study was to evaluate the quantitative relationships between high intensity signals (HIS) in the plaque on TOF-MRA and IPH or LRNC volumes as measured by multicontrast weighted CMR. METHODS: Seventy six patients with a suspected carotid artery stenosis or carotid plaque by ultrasonography underwent multicontrast carotid CMR. HIS presence and volume were measured from TOF-MRA MIP images while IPH and LRNC volumes were separately measured from multicontrast CMR. RESULTS: For detecting IPH, HIS on MIP images overall had high specificity (100.0%, 95% CI: 93.0 - 100.0%) but relatively low sensitivity (32%, 95% CI: 20.8 - 47.9%). However, the sensitivity had a significant increasing relationship with underlying IPH volume (p = 0.033) and degree of stenosis (p = 0.022). Mean IPH volume was 2.7 times larger in those with presence of HIS than in those without (142.8 ± 97.7 mm(3) vs. 53.4 ± 56.3 mm(3), p = 0.014). Similarly, mean LRNC volume was 3.4 times larger in those with HIS present (379.8 ± 203.4 mm(3) vs. 111.3 ± 122.7 mm(3), p = 0.001). There was a strong correlation between the volume of the HIS region and the IPH volume measured from multicontrast CMR (r = 0.96, p < 0.001). CONCLUSION: MIP images are easily reformatted from three minute, routine, clinical TOF sequences. High intensity signals in carotid plaque on TOF-MRA MIP images are associated with increased intraplaque hemorrhage and lipid-rich necrotic core volumes. The technique is most sensitive in patients with moderate to severe stenosis.

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.

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.

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.