Non-Invasive Retinal Blood Vessel Wall Measurements with Polarization-Sensitive Optical Coherence Tomography for Diabetes Assessment: A Quantitative Study.

Diabetes affects the structure of the blood vessel walls. Since the blood vessel walls are made of birefringent organized tissue, any change or damage to this organization can be evaluated using polarization-sensitive optical coherence tomography (PS-OCT). In this paper, we used PS-OCT along with the blood vessel wall birefringence index (BBI = thickness/birefringence2) to non-invasively assess the structural integrity of the human retinal blood vessel walls in patients with diabetes and compared the results to those of healthy subjects. PS-OCT measurements revealed that blood vessel walls of diabetic patients exhibit a much higher birefringence while having the same wall thickness and therefore lower BBI values. Applying BBI to diagnose diabetes demonstrated high accuracy (93%), sensitivity (93%) and specificity (93%). PS-OCT measurements can quantify small changes in the polarization properties of retinal vessel walls associated with diabetes, which provides researchers with a new imaging tool to determine the effects of exercise, medication, and alternative diets on the development of diabetes.

Quantitative model for assessment of lower-extremity perfusion in patients with diabetes.

BACKGROUND: Although diabetic and atherosclerotic vascular diseases have different pathophysiological mechanisms, the screening methods currently used for diabetic lower-extremity vascular diseases are mainly based on the evaluation methods used for atherosclerotic vascular diseases. Thus, assessment of microvascular perfusion is of great importance in early detection of lower-extremity ischemia in diabetes. PURPOSE: This cross-sectional study aimed to develop a quantitative model for evaluating lower-extremity perfusion. METHODS: We recruited 57 participants (14 healthy participants and 43 diabetes patients, of which 16 had lower-extremity arterial disease [LEAD]). All participants underwent technetium-99 m sestamibi (99mTc-MIBI) scintigraphy and ankle-brachial index (ABI) examination. We derived two key perfusion kinetics indices named activity perfusion index (API) and basal perfusion index (BPI). This study was registered in ClinicalTrials.gov (URL: https://www. CLINICALTRIALS: gov, NCT02752100). RESULTS: The estimated limb perfusion values in our lower-extremity perfusion assessment (LEPA) model showed excellent consistency with the actual measured data. Diabetes patients showed reduced lower-extremity perfusion in comparison with the control group (BPI: 106.21 ± 11.99 vs. 141.56 ± 17.38, p < 0.05; API: 12.34 ± 3.27 vs. 14.56 ± 3.12, p < 0.05). Using our model, the reductions in lower-extremity perfusion could be detected early in approximately 96.30% of diabetes patients. Patients with LEAD showed more severe reductions in lower-extremity perfusion than diabetes patients without LEAD (BPI: 47.85 ± 20.30 vs. 106.21 ± 11.99, p < 0.05; API: 7.06 ± 1.70 vs. 12.34 ± 3.27, p < 0.05). Discriminant analysis using API and BPI could successfully screen all diabetes patients with LEAD with a sensitivity of 100% and specificity of 80.77%. CONCLUSIONS: We established a LEPA model that could successfully assess lower-extremity microvascular perfusion in diabetes patients. This model has important application value for the recognition of early-stage LEAD in patients with diabetes.

Atherosclerosis Burdens in Diabetes Mellitus: Assessment by PET Imaging.

Arteriosclerosis and its sequelae are the most common cause of death in diabetic patients and one of the reasons why diabetes has entered the top 10 causes of death worldwide, fatalities having doubled since 2000. The literature in the field claims almost unanimously that arteriosclerosis is more frequent or develops more rapidly in diabetic than non-diabetic subjects, and that the disease is caused by arterial inflammation, the control of which should therefore be the goal of therapeutic efforts. These views are mostly based on indirect methodologies, including studies of artery wall thickness or stiffness, or on conventional CT-based imaging used to demonstrate tissue changes occurring late in the disease process. In contrast, imaging with positron emission tomography and computed tomography (PET/CT) applying the tracers 18F-fluorodeoxyglucose (FDG) or 18F-sodium fluoride (NaF) mirrors arterial wall inflammation and microcalcification, respectively, early in the course of the disease, potentially enabling in vivo insight into molecular processes. The present review provides an overview of the literature from the more than 20 and 10 years, respectively, that these two tracers have been used for the study of atherosclerosis, with emphasis on what new information they have provided in relation to diabetes and which questions remain insufficiently elucidated.

Xenon-enhanced computed tomography assessment of brown adipose tissue distribution and perfusion in lean, obese, and diabetic primates.

OBJECTIVE: This study aimed to validate xenon-enhanced computed tomography (XECT) for the detection of brown adipose tissue (BAT) and to use XECT to assess differences in BAT distribution and perfusion between lean, obese, and diabetic nonhuman primates (NHPs). METHODS: Whole-body XECT imaging was performed in anesthetized rhesus and vervet monkeys during adrenergic stimulation of BAT thermogenesis. In XECT images, BAT was identified as fat tissue that, during xenon inhalation, underwent significant radiodensity enhancement compared with subcutaneous fat. To measure BAT blood flow, BAT radiodensity enhancement was measured over time on the six computed tomography scans acquired during xenon inhalation. Postmortem immunohistochemical staining was used to confirm imaging findings. RESULTS: XECT was able to correctly identify all BAT depots that were confirmed at necropsy, enabling construction of the first comprehensive anatomical map of BAT in NHPs. A significant decrease in BAT perfusion was found in diabetic animals compared with obese animals and healthy animals, as well as absence of axillary BAT and significant reduction of supraclavicular BAT in diabetic animals compared with obese and lean animals. CONCLUSIONS: The use of XECT in NHP models of obesity and diabetes allows the analysis of the impact of metabolic status on BAT mass and perfusion.

Comparison of Risk Assessment Strategies for Patients with Diabetes Mellitus and Stable Chest Pain: A Coronary Computed Tomography Angiography Study.

BACKGROUND: To compare two risk assessment strategies to identify individuals likely to benefit from further imaging testing in patients with diabetes mellitus (DM) and stable chest pain (SCP) suspected of obstructive coronary artery disease (CAD). METHODS: 602 DM patients referred to coronary computed tomography angiography (CCTA) for SCP were included. They were divided into high- and low-risk groups according to the 2016 National Institute of Health and Care Excellence guideline-determined strategy (NICE strategy) which focused on symptom evaluation and 2019 European Society of Cardiology guideline-determined strategy (ESC strategy) which was based on pretest probability (PTP) sequentially determined by the ESC-PTP estimator and risk factor-weighted clinical likelihood (RF-CL) model, respectively. The associations of clinical outcomes with risk groups and net reclassification improvement (NRI) were evaluated. RESULTS: The NICE and ESC strategy classified 44% and 39% patients into the low-risk group, respectively. Compared to the NICE strategy, the ESC strategy indicated stronger associations between risk groups and events (hazard ratios: 4.24 versus 1.91), intensive clinical management, and a positive NRI (27.71%, p < 0.0001). The application of the RF-CL model ameliorated the underestimation of risk in patients with borderline ESC-PTP, which principally account for the improvement of the ESC strategy. CONCLUSION: Compared to the NICE strategy, the ESC strategy seemed to be associated with greater efficiency in identifying high risk individuals in patients with DM and SCP.

Quantitative assessment of the mandibular condyle in patients with diabetes mellitus using diffusion-weighted magnetic resonance imaging.

OBJECTIVE: The purpose of this study was to quantitatively assess the mandibular condyle in patients with diabetes mellitus (DM) using the apparent diffusion coefficient (ADC) on diffusion-weighted magnetic resonance imaging (DWI). STUDY DESIGN: 102 patients with DM and temporomandibular joint (TMJ) pain who underwent magnetic resonance imaging (MRI) examination of the TMJs at our hospital between August 2006 and March 2020 were included in this study. 112 patients with temporomandibular disorders (TMD) who underwent MRI examination at our hospital between April 2019 and March 2020 were included as controls. The MRI findings were compared between the two groups. RESULTS: The mean ADC values of the mandibular condyle in patients with DM were significantly greater than the controls (P < 0.01). Receiver operating characteristic (ROC) curve analysis revealed a cutoff of 0.98 for the ADC values of the mandibular condyle in patients with DM. CONCLUSION: This study found that the ADC on DWI could be used for the quantitative assessment of the mandibular condyle in patients with DM. DWI might serve as a new and noninvasive method to assess the presence of DM.

Quantitative assessment of the mandibular bone marrow of diabetes mellitus patients using diffusion-weighted magnetic resonance imaging.

PURPOSE: The purpose of this study was to assess quantitatively the mandibular bone marrow of patients with and without diabetes mellitus (DM) using the apparent diffusion coefficient (ADC) values on diffusion-weighted imaging (DWI). METHODS: 65 DM patients (28 men, 37 women, 29-84 years of age, mean age 55.7 ± 15.7 years) and age-, sex- and periodontitis stage-matched 65 non-DM patients who had underwent MRI between April 2006 and March 2018 were included in this study. The ADC was calculated using the ADC visualization tool implemented in a dedicated off-line workstation. The regions of interest (ROI) were manually placed on the ADC map on which the mandibular bone marrow from the lower first molar to the lower second molar was observed in patients with and without DM. Statistical analysis was performed using the Mann-Whitney U test and receiver operating characteristic (ROC) curve analysis. P values < 0.05 were considered statistically significant. RESULTS: The mean ADC values of the mandibular bone marrow of patients with and without DM were 1.18 ± 0.21 × 10-3 mm2/s and 0.83 ± 0.14 × 10-3 mm2/s, respectively. The ADC values of DM patients were significantly higher than those of patients without DM. CONCLUSION: The ADC values allowed the quantitative evaluation of the mandibular bone marrow of DM patients. DWI might serve as a new and noninvasive method to assess the presence of DM.

Correlation between fractional flow reserve and instantaneous wave-free ratio with morphometric assessment by optical coherence tomography in diabetic patients.

Currently there is lack of data regarding the use of optical coherence tomography (OCT) to depict the hemodynamic relevance of coronary stenoses in diabetic patients. We sought to assess the diagnostic accuracy of OCT-derived morphologic assessment in identifying hemodynamically significant coronary lesions as determined by both, the resting instantaneous wave-free ratio (iFR) and the hyperemic fractional flow reserve (FFR) in diabetic patients. Diabetic patients presenting with at least one intermediate coronary lesion were prospectively and consecutively enrolled. All lesions were systematically assessed by iFR, FFR and OCT. A total of 41 intermediate lesions were analysed. Mean iFR and FFR values were 0.90 ± 0.04 and 0.81 ± 0.06, respectively (intra-class correlation coefficient 0.49; 95% CI 0.22-0.79). A moderate correlation between iFR and OCT derived minimal lumen diameter (MLD, r = 0.49) and minimal lumen area (MLA, r = 0.50) was found. Conversely, there was a poor correlation between FFR and OCT-derived MLD (r = 0.34) and MLA (r = 0.32). The diagnostic efficiency of MLA and MLD to identify iFR significant stenoses showed an AUC of 0.82 (95% CI 0.69-0.95) for MLD and 0.83 (95% CI 0.71-0.96) for MLA. A worse diagnostic efficiency was found when FFR was used as the reference with an AUC of 0.71 (95% CI 0.54-0.87) for MLD and 0.70 (95% CI 0.53-0.87). OCT-derived MLA and MLD were the strongest independent anatomic predictors of abnormal iFR and FFR values. In diabetic patients, OCT-derived MLA and MLD showed a moderate diagnostic efficiency in identifying functionally significant coronary stenoses by FFR or iFR. In diabetics, anatomic OCT measurements better predicted resting than FFR-determined physiologically significant lesions.

Management of Diabetes Mellitus Before 18F-Fluorodeoxyglucose PET/CT: A Nationwide Patient-Centered Assessment of Approaches to Examination Preparation.

PURPOSE: The aim of this study was to perform, from the patient's point of view, a nationwide assessment of nuclear medicine practices regarding diabetic management before 18F-fluorodeoxyglucose (FDG) PET/CT for oncologic indications. METHODS: This prospective observational study was exempt from institutional review board oversight. Sixty-five nuclear medicine scheduling lines (33 academic, 32 private practice, 12-17 in each of the five US regions) were called using a prewritten script under the guise of a nonexpert patient's family member about scheduling a patient with diabetes with "cancer" for FDG PET/CT. Each center was called three times on three different days. The following data were collected: (1) blood glucose threshold for rescheduling an examination, (2) when or if to stop various medications, (3) fasting requirements, and (4) time-of-day scheduling preferences. Withheld information was not specifically requested. Descriptive statistics were calculated. RESULTS: There were 195 phone calls (mean duration, 2.9 min; range, 2-6 min). Relevant information was often withheld; withholding rates were as follows: blood glucose threshold, 71% (138 of 195); short-acting insulin instructions, 30% (59 of 195); long-acting insulin instructions, 99% (193 of 195); metformin instructions, 88% (179 of 195); fasting duration, 37% (72 of 195); and time-of-day scheduling preference, 91% (177 of 195). Mean provided data were as follows: blood glucose threshold, 195 mg/dL (range, 150-210 mg/dL); short-acting insulin withholding, 4.9 hours (range, 4-8 hours); long-acting insulin withholding, 12 hours (range, 12-24 hours); fasting duration, 5 hours (range, 4-8 hours); and preferred examination time, 91% (177 of 195). When specified (n = 18), morning scheduling was preferred (8% [15 of 195] versus 2% [3 of 195]). CONCLUSIONS: Diabetes-specific information is commonly withheld by nuclear medicine call centers throughout the United States when discussing oncologic FDG PET/CT despite local and national policies indicating its importance.

Noncontrast MR angiography: An update.

Both computed tomography (CT) angiography (CTA) and contrast-enhanced MR angiography (CEMRA) have proven to be useful and accurate cross-sectional imaging modalities over a wide range of vascular territories and vascular disorders. A key advantage of MRA is that, unlike CTA, it can be performed without the administration of a contrast agent. In this review article we consider the motivations for using noncontrast MRA, potential contrast mechanisms, imaging techniques, advantages, and drawbacks with respect to CTA and CEMRA, and the level of evidence for using the various MRA techniques. In addition, we explore new developments that promise to expand the reliability and range of clinical applications for noncontrast MRA, along with functional MRA capabilities not available with CTA or CEMRA. Level of Evidence: 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2019;49:355-373.

Weighted averaging in spectroscopic studies improves statistical power.

PURPOSE: In vivo MRS is often characterized by a spectral signal-to-noise ratio (SNR) that varies highly between experiments. A common design for spectroscopic studies is to compare the ratio of two spectral peak amplitudes between groups, e.g. individual PCr/γ-ATP ratios in 31 P-MRS. The uncertainty on this ratio is often neglected. We wished to explore this assumption. THEORY: The canonical theory for the propagation of uncertainty on the ratio of two spectral peaks and its incorporation in the Frequentist hypothesis testing framework by weighted averaging is presented. METHODS: Two retrospective re-analyses of studies comparing spectral peak ratios and one prospective simulation were performed using both the weighted and unweighted methods. RESULTS: It was found that propagating uncertainty correctly improved statistical power in all cases considered, which could be used to reduce the number of subjects required to perform an MR study. CONCLUSION: The variability of in vivo spectroscopy data is often accounted for by requiring it to meet an SNR threshold. A theoretically sound propagation of the variable uncertainty caused by quantifying spectra of differing SNR is therefore likely to improve the power of in vivo spectroscopy studies. Magn Reson Med 78:2082-2094, 2017. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Ultrasound assessment of thyroid gland volume in diabetic patients without overt thyroid disease.

BACKGROUND: Diabetes mellitus and thyroid disease are known to mutually influence each other. Thyroid disease can worsen glycaemic control in diabetes, and patients with diabetes mellitus have increased incidence of thyroid disorders such as increase in size, compared to the normal population. AIMS/OBJECTIVES: The aim of the study was to sonographically assess thyroid gland volume in Nigerian adult diabetic patients and compare with apparently healthy adults (controls). SUBJECTS AND METHODS: The study setting was the Department of Radiology, University of Benin Teaching Hospital (UBTH) Nigeria. The thyroid gland in 120 diabetic subjects and equal number of apparently healthy controls was scanned with a 5-12 MHz linear transducer of a SONOACE X4 Machine. Thyroid gland volume was assessed. Statistical analysis was done with Statistical Package for the Social Sciences (SPSS) version 17 (SPSS Inc, Chicago, IL, USA). RESULTS: Diabetics had significantly increased thyroid volume compared to age matched male and female control subjects (11.5 ± 5.2 cm3 vs 7.4 ± 1.9 cm3; P< 0.001 for males) and (9.9 ± 6.2 cm3 vs 7.1 ± 3.4 cm3; P< 0.001 for females) respectively. Gender did not significantly influence thyroid volume among diabetics. CONCLUSION: Diabetics have higher thyroid gland dimensions, compared to apparently healthy subjects. Gland proliferation from circulating insulin may play a role. This is not influenced by gender.

Impact of Total Risk Management on Coronary Plaque Regression in Diabetic Patients with Acute Coronary Syndrome.

AIM: Diabetic patients with coronary artery disease have a high incidence of cardiovascular events, which was associated with increased coronary plaque volume. Low-density lipoprotein cholesterol (LDL-C) and blood pressure (BP) play pivotal roles in the progression of coronary plaque. Several trials have shown that intervention for a single risk factor reduced the development of coronary plaque progression. However, it remained uncertain whether total risk management for LDL-C, BP, and glycosylated Hb (HbA1c) has a beneficial effect on coronary plaque volume in diabetic patients. METHODS: This study was a sub-study of the JAPAN-ACS that was a prospective, randomized, open-label trial that evaluated the impact of intensive lipid-lowering therapy on coronary plaque volume in patients with acute coronary syndrome (ACS). Among a total of 252 patients, 73 diabetic patients were analyzed. We examined the impact of total risk management (LDL-C ＜80 mg/dL, systolic BP ＜130 mmHg, and HbA1c ＜6.5%) on changes in coronary plaque volume. The patients were divided into four groups according to the number of risk factors that achieved the target value. RESULTS: Baseline characteristics were similar among the groups. The degree of coronary plaque regression was greater in patients who achieved total risk management. The number of risk factors that achieved the target level was associated with the extent of the coronary plaque volume reduction in a dose-dependent manner. CONCLUSION: Total risk management that focused on LDL-C, BP, and HbA1c had a beneficial impact on the coronary plaque regression in diabetic patients with ACS.

64Cu-DOTATATE for Noninvasive Assessment of Atherosclerosis in Large Arteries and Its Correlation with Risk Factors: Head-to-Head Comparison with 68Ga-DOTATOC in 60 Patients.

UNLABELLED: The somatostatin receptor subtype 2 is expressed on macrophages, an abundant cell type in the atherosclerotic plaque. Visualization of somatostatin receptor subtype 2, for oncologic purposes, is frequently made using the DOTA-derived somatostatin analogs DOTATOC or DOTATATE for PET. We aimed to compare the uptake of the PET tracers (68)Ga-DOTATOC and (64)Cu-DOTATATE in large arteries, in the assessment of atherosclerosis by noninvasive imaging technique, combining PET and CT. Further, the correlation of uptake and cardiovascular risk factors was investigated. METHODS: Sixty consecutive patients with neuroendocrine tumors underwent both (68)Ga-DOTATOC and (64)Cu-DOTATATE PET/CT scans, in random order. For each scan, the maximum and mean standardized uptake values (SUVs) were calculated in 5 arterial segments. In addition, the blood-pool-corrected target-to-background ratio was calculated. Uptake of the tracers was correlated with cardiovascular risk factors collected from medical records. RESULTS: We found detectable uptake of both tracers in all arterial segments studied. Uptake of (64)Cu-DOTATATE was significantly higher than (68)Ga-DOTATOC in the vascular regions both when calculated as maximum and mean uptake. There was a significant association between Framingham risk score and the overall maximum uptake of (64)Cu-DOTATATE using SUV (r = 0.4; P = 0.004) as well as target-to-background ratio (r = 0.3; P = 0.04), whereas no association was found with (68)Ga-DOTATOC. The association of risk factors and maximum SUV of (64)Cu-DOTATATE was found driven by body mass index, smoking, diabetes, and coronary calcium score (P < 0.001, P = 0.01, P = 0.005, and P = 0.03, respectively). CONCLUSION: In a series of oncologic patients, vascular uptake of (68)Ga-DOTATOC and (64)Cu-DOTATATE was found, with highest uptake of the latter. Uptake of (64)Cu-DOTATATE, but not of (68)Ga-DOTATOC, was correlated with cardiovascular risk factors, suggesting a potential role for (64)Cu-DOTATATE in the assessment of atherosclerosis.

Assessment of carotid atherosclerosis, intraplaque neovascularization, and plaque ulceration using quantitative contrast-enhanced ultrasound in asymptomatic patients with diabetes mellitus.

AIMS: Patients with diabetes mellitus (DM) are at severely increased risk of developing atherosclerosis. Intraplaque neovascularization (IPN) and plaque ulceration are markers of the vulnerable plaque, which is at an increased risk of rupture and may lead to cardiovascular events. The aim of this study was to assess the prevalence of subclinical carotid atherosclerosis, intraplaque neovascularization (IPN), and plaque ulceration in asymptomatic patients with DM. METHODS AND RESULTS: A total of 51 asymptomatic patients with DM underwent standard carotid ultrasound in conjunction with contrast-enhanced ultrasound (CEUS) to assess the prevalence of subclinical atherosclerosis, IPN, and plaque ulceration. Subclinical atherosclerosis was defined as the presence of atherosclerotic plaque, according to the Mannheim consensus. Semi-automated quantification software was used to assess IPN in suitable plaques. Plaque ulceration was defined as a disruption of the plaque-lumen border of ≥ 1 × 1 mm. A total of 408 carotid segments in 102 carotid arteries were investigated. Forty-six (90%) patients had subclinical atherosclerotic plaques, with a median plaque thickness of 2.4 mm (inter-quartile range 1.9-3.0). CEUS revealed IPN in 88% of the patients. In 10 carotid segments (8%), the plaque had an ulcerated surface. The presence of IPN could not be predicted by the presence of clinical characteristics including complications of DM (P > 0.05). CONCLUSION: Patients with DM have a high prevalence (90%) of subclinical carotid atherosclerosis. Severe IPN and plaque ulceration, which are markers of the vulnerable plaque type, were detected in, respectively, 13 and 9% of these patients.

Quantitative and qualitative bone assessment of the posterior mandible in patients with diabetes mellitus: a cone beam computed tomography study.

UNLABELLED: Evaluation of mandibular bone features is very important for the diagnosis, treatment planning and management of dental procedures such as osseointegrated implants. AIM: To evaluate the bone quantity and quality of the posterior region of the mandible using the CBCT technique for implant planning in patients with diabetes mellitus. METHODS: Twenty-three patients with diabetes mellitus and 27 control subjects participated in the study. Mandibular bone measurements were performed on the cone beam computed tomography (CBCT) images. One previously calibrated oral radiologist with CBCT experience measured the distance from mandibular canal to alveolar ridge and the distance from bucal to lingual cortical wall. Also, it was assessed the bone quality of each region of interest, by measuring the bone mineral density. The study protocol was approved by the local Ethics Committee. RESULTS: The study revealed the presence of significant correlations between bone quality and values ofglycosylated hemoglobin and a significant association between patient gender and bone type. There is a significant inverse correlation between the values of cortical and trabecular bone density in the posterior region of the mandible and HbA1c. CONCLUSIONS: In conclusion the use of CBCT in preoperative bone measurements will help provide valuable information about the quantity and quality of bone before the placement of dental implants.