Safety findings after intravenous administration of sulfur hexafluoride microbubbles to 463,434 examinations at 24 centers.

OBJECTIVES: We aimed to evaluate the safety of the ultrasound contrast agent sulfur hexafluoride microbubbles in a large group of patients referred for routine contrast-enhanced ultrasound (CEUS). METHODS: A retrospective assessment was made of all patients that received sulfur hexafluoride microbubbles intravenously for CEUS at 24 centers between January 2006 and April 2019. Patient demographic details, examination type, and the dose of sulfur hexafluoride microbubbles administered were recorded with specific adverse events (AEs) documentation tools at each center. All AEs were recorded as serious or non-serious. Non-serious AEs were classified by intensity as mild, moderate, or severe according to ACR criteria. The frequencies of AEs across patient subgroups were compared using the chi-square test. RESULTS: A total of 463,434 examinations were evaluated. Overall, 157 AEs (153 [0.033%] non-serious; 4 [0.001%] serious) were reported after sulfur hexafluoride microbubbles administration, giving an AE frequency of 0.034% (157/463,434). Among the non-serious AEs, 66 (0.014%) were mild, 70 (0.015%) moderate, and 17 (0.004%) severe in intensity. The liver was the most common examination site, presenting an AE frequency of 0.026%. The highest AE frequency (0.092%) was for patients undergoing CEUS for vascular disease. There were no significant gender differences in either the total number or the severity of non-serious AEs (chi-square = 2.497, p = 0.287). The onset of AEs occurred within 30 min of sulfur hexafluoride microbubbles administration in 91% of cases. CONCLUSION: The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare, confirming that sulfur hexafluoride microbubbles are appropriate for routine CEUS applications. KEY POINT: • The frequency of AEs to sulfur hexafluoride microbubbles is very low and severe reactions are rare.

Extracellular volume fraction measurements derived from the longitudinal relaxation of blood-based synthetic hematocrit may lead to clinical errors in 3 T cardiovascular magnetic resonance.

BACKGROUND: The extracellular volume (ECV), derived from cardiovascular magnetic resonance (CMR) T1 mapping, is a biomarker of the extracellular space in the myocardium. The hematocrit (HCT), measured from venipuncture, is required for ECV measurement. We test the clinic values of synthetic ECV, which is derived from the longitudinal relaxation of blood-based (T1blood) synthetic hematocrit in 3 T CMR. METHODS: A total of 226 subjects with CMR T1 mapping and HCT measurement taken on the same day as the CMR were retrospectively enrolled and randomly split into derivation (n = 121) and validation (n = 105) groups, comprising healthy subjects (n = 45), type 2 diabetes mellitus (T2DM) patients (n = 60), hypertrophic cardiomyopathy (HCM) patients (n = 93), and 28 other patients. Correlation of T1blood with the measured HCT (HCTm) was established in the derivation group and used in both the derivation and the validation groups. The relationships between the ECV values derived from both the synthetic HCT (HCTsyn) and HCTm were explored. In addition, the differences in the ECV values among the HC, T2DMs, and HCMs were compared. RESULTS: Regression between the HCTm and 1/T1blood was linear (R2 = 0.19, p < 0.001), and the regression equation was: HCTsyn = [561.6*(1/T1blood)] + 0.098 in the derivation group. The measured ECV (ECVm) was strongly correlated with the synthetic ECV (ECVsyn) (R2 = 0.87, p < 0.001) and mildly correlated with the difference between the ECVsyn and ECVm (R2 = 0.10, p < 0.001) in the derivation group. Also in this group, the ECVm was larger in T2DMs than that in healthy cohort (29.1 ± 3.1% vs. 26.4 ± 2.4%, p = 0.002), whereas, the ECVsyn did not differ between T2DMs and healthy cohort (28.3 ± 2.9% vs. 26.9 ± 2.2%, p = 0.064). Compared with the healthy cohort, the HCMs were associated with higher ECVsyn and ECVm of the mid-ventricle in both the derivation and the validation groups. Using our center's normal cut-off of 31.8%, the use of ECVsyn would lead to a 6-25% incorrect categorization of patients in the derivation and validation groups. CONCLUSIONS: ECVsyn derived from HCTsyn may lead to clinical errors in 3 T CMR, especially for patients who have only a subtle elevation in ECV.

Corrigendum: Dynamic evolution of left ventricular strain and microvascular perfusion assessed by speckle tracking echocardiography and myocardial contrast echocardiography in diabetic rats: effect of dapagliflozin.

[This corrects the article DOI: 10.3389/fcvm.2023.1109946.].

Two way workable microchanneled hydrogel suture to diagnose, treat and monitor the infarcted heart.

During myocardial infarction, microcirculation disturbance in the ischemic area can cause necrosis and formation of fibrotic tissue, potentially leading to malignant arrhythmia and myocardial remodeling. Here, we report a microchanneled hydrogel suture for two-way signal communication, pumping drugs on demand, and cardiac repair. After myocardial infarction, our hydrogel suture monitors abnormal electrocardiogram through the mobile device and triggers nitric oxide on demand via the hydrogel sutures' microchannels, thereby inhibiting inflammation, promoting microvascular remodeling, and improving the left ventricular ejection fraction in rats and minipigs by more than 60% and 50%, respectively. This work proposes a suture for bidirectional communication that acts as a cardio-patch to repair myocardial infarction, that remotely monitors the heart, and can deliver drugs on demand.

Multi-parameter cardiac magnetic resonance imaging detects anthracycline-induced cardiotoxicity in rabbits model.

Background: Cardiac magnetic resonance (CMR) quantitative T1 and T2 mapping offers a non-invasive means to evaluate early cardiotoxicity changes. This study aimed to pinpoint the earliest CMR indicators of myocardial injury in Anthracycline-induced cardiotoxicity (AIC) and to elucidate the connections between these CMR indicators and associated pathological indicators. Methods: A total of 34 rabbits were administered doxorubicin at a dosage of 1 mg/kg/weekly. The study incorporated six 3T CMR scan time points: baseline, and at intervals of four, six, eight, twelve, and sixteen weeks. Cine, T1 and T2 mapping sequences assessed the left ventricular ejection fraction (LVEF), native T1, extracellular volume fraction (ECV), and T2 values. Following each time point, three rabbits were sacrificed for histological analysis involving Hematoxylin and eosin (H&E), Masson, TUNEL, and microvascular density (MVD) stains. Spearman correlations and linear mixed model analysis served in the statistical analysis. Results: Diverse degrees of alternation were recorded in LVEF, native T1, T2, and ECV over time. LVEF declined to 49.0 ± 2.6 % at 12 weeks from the baseline of 53.4 ± 3.2 %, p < 0.001. Native T1 values increase from the baseline (1396.5 ± 79.2 ms) until 8 weeks (1498.8 ± 95.4 ms, p < 0.001). T2 values increased from the baseline (36.6 ± 3.3 ms) within 4 weeks of initiation (37.5 ± 3.4, p = 0.02) and remained elevated through 16 weeks (42.8 ± 0.3, p < 0.01). ECV was elevated at 8 weeks (33.9 ± 3.8 %, p = 0.005) compared to the baseline (30.2 ± 2.5 %). By week 12, myocardial edema and increased CVF were apparent (p = 0.04 and = 0.001, respectively). The area under ROC curve for positive CMR presence and the gold standards were 0.87 (T2-ROC, 4 weeks) and 0.92 (LVEF&BNP-ROC, 12 weeks). Conclusion: T1 and T2 mapping are effective tools for cardiotoxicity detection and monitoring. The prolongation of T2 value emerged as the most consistent and early-onset indicator.

Dynamic evolution of left ventricular strain and microvascular perfusion assessed by speckle tracking echocardiography and myocardial contrast echocardiography in diabetic rats: Effect of dapagliflozin.

Background: This experimental study aimed to determine the dynamic changes in myocardial strain and microvascular perfusion in diabetic rats by comprehensive echocardiography while evaluating the effect of dapagliflozin (DAPA). Materials and methods: Male Sprague-Dawley rats (n = 128) were randomly divided into four groups based on the presence or absence of a high-fat diet and streptozotocin-induced diabetes with or without DAPA treatment (n = 32/group). Serial conventional ultrasound, two-dimensional speckle tracking echocardiography (2D-STE) and myocardial contrast echocardiography (MCE) were performed at 2, 4, 6, and 8 weeks, and left ventricular global longitudinal strain (GLS), myocardial blood flow velocity (MBFV), myocardial blood flow (MBF), and myocardial blood volume (MBV) were determined. All animals were sacrificed immediately after the last echo measurement for histopathological assessment. Results: Despite similar conventional Doppler-echo indexes among the groups at 2, 4, 6, and 8 weeks (p > 0.05), left ventricular GLS, MBFV, MBF, and MBV were decreased at 8 weeks in diabetic rats (p < 0.05) as detected by both 2D-STE and MCE. These indexes were significantly improved at 6 and 8 weeks after treatment with DAPA for diabetic rats (p < 0.05), reaching similar values observed in non-diabetic controls. DAPA treatment was associated with increased myocardial vacuolization and microvessel density and reduced interstitial fibrosis in diabetic rats. Conclusions: Combined 2D-STE and MCE is sensitive for detecting left ventricular deformity and impaired microvascular perfusion in prediabetes and the early stage of diabetes mellitus. DAPA exerts a beneficial effect on protecting myocardial perfusion in diabetic rats.

Sex Differences in Type 2 Diabetes Mellitus-Related Left Ventricular Remodeling: A Cardiovascular Magnetic Resonance Study.

Background: The purpose of this study was to evaluate the sex differences in myocardial structure, tissue characteristics, and myocardial function in type 2 diabetes mellitus (T2DM) patients. Methods: A total of 62 T2DM patients and 40 controls were prospectively recruited for the study. All the participants were scanned using cardiovascular magnetic resonance (CMR) cine and underwent native and postcontrast T1 mapping to obtain left ventricular (LV) structure, function, and tissue characteristics. The differences between the control and T2DM patients were compared in males and females, respectively. Results: For myocardial structure, T2DM was associated with a larger ratio of myocardial mass to end-diastolic volume (MVR, T2DM: 0.87 ± 0.20 vs. controls: 0.73 ± 0.14, p = 0.008) and thicker wall thickness (WT, T2DM: 6.5 ± 1.1 mm vs. controls: 5.6 ± 1.0 mm, p = 0.002) in females. For tissue characteristics, T2DM was associated with a similar T1 value, elevated extracellular volume fraction (ECV, T2DM: 27.8 ± 3.6% vs. controls: 25.1 ± 2.5%, p = 0.002), and increased extracellular matrix volume index (ECMVi, T2DM: 15.8 ± 3.8 ml/m2 vs. controls: 13.4 ± 2.7 ml/m2, p = 0.008) in males. For myocardial function, in male, compared with control, T2DM was associated with decreased peak longitudinal diastolic strain rate (PLDSR, T2DM: 0.97 ± 0.19 1/s vs. control: 1.13 ± 0.29 1/s, p = 0.030). Conclusions: There might be sex differences in myocardial remodeling induced by T2DM, including LV structural concentric remodeling in female patients and extracellular matrix remodeling and subclinical diastolic dysfunction in male patients.

Stress CMR T1-mapping technique for assessment of coronary microvascular dysfunction in a rabbit model of type II diabetes mellitus: Validation against histopathologic changes.

Background: Coronary microvascular dysfunction (CMD) is an early character of type 2 diabetes mellitus (T2DM), and is indicative of adverse events. The present study aimed to validate the performance of the stress T1 mapping technique on cardiac magnetic resonance (CMR) for identifying CMD from a histopathologic perspective and to establish the time course of CMD-related parameters in a rabbit model of T2DM. Methods: New Zealand white rabbits (n = 30) were randomly divided into a control (n = 8), T2DM 5-week (n = 6), T2DM 10-week (n = 9), and T2DM 15-week (n = 7) groups. The CMR protocol included rest and adenosine triphosphate (ATP) stress T1-mapping imaging using the 5b(20b)3b-modified look-locker inversion-recovery (MOLLI) schema to quantify stress T1 response (stress ΔT1), and first-pass perfusion CMR to quantify myocardial perfusion reserve index (MPRI). After the CMR imaging, myocardial tissue was subjected to hematoxylin-eosin staining to evaluate pathological changes, Masson trichrome staining to measure collagen volume fraction (CVF), and CD31 staining to measure microvascular density (MVD). The associations between CMR parameters and pathological findings were determined using Pearson correlation analysis. Results: The stress ΔT1 values were 6.21 ± 0.59%, 4.88 ± 0.49%, 3.80 ± 0.40%, and 3.06 ± 0.54% in the control, T2DM 5-week, 10-week, and 15-week groups, respectively (p < 0.001) and were progressively weakened with longer duration of T2DM. Furthermore, a significant correlation was demonstrated between the stress ΔT1 vs. CVF and MVD (r = -0.562 and 0.886, respectively; p < 0.001). Conclusion: The stress T1 response correlated well with the histopathologic measures in T2DM rabbits, indicating that it may serve as a sensitive CMD-related indicator in early T2DM.

Early and dynamic detection of doxorubicin induced cardiotoxicity by myocardial contrast echocardiography combined with two-dimensional speckle tracking echocardiography in rats.

Background: Anthracycline-induced cardiotoxicity is well-known as a side effect of chemotherapy. Currently, clinical imaging techniques are not capable to detect doxorubicin (DOX)-induced cardiotoxicity before a functional decline. The purpose of this study was to evaluate whether myocardial contrast echocardiography (MCE) can dynamically monitor the cardiac changes in the early stage in the DOX-induced rat model of cardiotoxicity. Methods: A weekly injection of 2.5 mg/kg of DOX was used to generate a rat model of cardiotoxicity. All groups underwent ultrasonic examinations including standard echocardiography, 2D speckle tracking echocardiography (2D-STE), and MCE. Then all rats were sacrificed immediately for histopathological evaluation. Results: A total of eight control rats and 32 DOX-treated rats were included in the study and grouped according to their treatment period. Decreased quantitative parameters of myocardial blood flow (MBF) (control vs. group 1: 133.31 ± 20.23 dB/s vs. 103.35 ± 21.60 dB/s, P = 0.048) and ß (control vs. group 2: 11.17 ± 1.48/s vs. 7.15 ± 1.23/s, P < 0.001) were observed after 2 and 4 weeks of treatment, respectively, while left ventricular global strain (control vs. group 3: -23.67 ± 3.92% vs. -16.01 ± 3.40%, P = 0.002) decreased after 6 weeks of treatment and left ventricular ejection fraction (LVEF) (control vs. group 4: 82.41 ± 3.20% vs. 70.89 ± 9.30%, P = 0.008) decreased after 8 weeks of treatment. The main histopathological features are increased myocardial vacuolization and interstitial fibrosis and decreased myocardial microvessel density. Conclusion: Compared with standard echocardiography and 2D-STE, MCE can accurately and non-invasively detect changes in early myocardial perfusion, demonstrating the clinical potential of continuous and dynamic monitoring of DOX-induced cardiotoxicity.

Histologic validation of stress cardiac magnetic resonance T1-mapping techniques for detection of coronary microvascular dysfunction in rabbits.

BACKGROUND: To investigate the diagnostic performance of stress cardiac magnetic resonance (CMR) T1-mapping for the detection of coronary microvascular dysfunction (CMD) by correlating microvascular density (MVD) and collagen volume fraction (CVF) with T1 response to adenosine triphosphate (ATP) stress (stress ΔT1) in rabbits. METHODS: Twenty-four New Zealand white rabbits were randomly divided into the CMD group induced by microembolization spheres (n = 10), sham-operated group (n = 5), and control group (n = 9). All rabbits underwent 3.0 T CMR, both rest and ATP stress T1-maps were obtained, and first-pass perfusion imaging was performed. Stress ΔT1 and myocardial perfusion reserve index (MPRI) were calculated. For the histologic study, each rabbit was sacrificed after CMR scanning. Left ventricular myocardial tissue was stained with Hematoxylin-eosin (H&E), Masson, and CD31, from which MVD and CVF were extracted. Pearson correlation analyses were performed to determine the strength of the association between the stress ΔT1 and both MVD and CVF. RESULTS: The stress ΔT1 values (CMD, 2.53 ± 0.37% vs. control, 6.00 ± 0.64% vs. Sham, 6.07 ± 0.97%, p < 0.001) and MPRI (CMD, 1.45 ± 0.13 vs. control, 1.94 ± 0.23, vs. sham, 1.89 ± 0.15, p < 0.001) were both lower in CMD rabbits compared with sham-operated and control rabbits. Further, the stress ΔT1 showed a high correlation with CVF (r = -0.806, p < 0.001) and MVD (r = 0.920, p < 0.001). CONCLUSIONS: Stress T1 response strongly correlates with pathological MVD and CVF, indicating that stress CMR T1 mapping can accurately detect microvascular dysfunction.

Assessment of right ventricular function using cardiovascular magnetic resonance in patients with type 2 diabetes mellitus.

BACKGROUND: Accurate evaluation of right ventricular (RV) function is always difficult due to its irregular shape and movement. Many indices have been proposed to assess RV function, but none have been universally accepted. This study evaluated RV function in type 2 diabetes mellitus (T2DM) patients using long-axis strain (LAS) and other traditional indices. METHODS: Fifty-seven patients with T2DM and 39 healthy controls were prospectively enrolled. Four-chamber cardiovascular magnetic resonance (CMR) and RV short-axis cine images were obtained from all participants to measure the tricuspid annular plane systolic excursion (TAPSE), RV ejection fraction (EF), peak longitudinal strain (PLS) and four LAS indices. The inter-and intraobserver variabilities were also calculated. RESULTS: Compared with healthy controls, T2DM was associated with a decreased LAS (apex/lateral wall) (-17.4%±4.2% vs. control, -19.7%±3.7%, P=0.008) and LAS (apex/middle point) (-17.5%±4.5% vs. control, -19.5%±3.9%, P=0.026), but both groups had a similar LAS (RV/lateral wall) and LAS (RV/middle point) (all P>0.05). After adjustments for age and body mass index, a significant difference was observed only for LAS (apex/lateral wall) (P=0.028). There were no significant differences in the TAPSE, RVEF and PLS (all P>0.05). LAS (apex/lateral wall) correlated with the TAPSE (r=-0.723, P<0.001), RVEF (r=-0.270, P=0.008) and PLS (r=0.210, P=0.040). The inter- and intraobserver variability of the LAS (apex/lateral wall) were lower than the other three LAS indices. CONCLUSIONS: Compared with traditional RV function indices, such as the TAPSE, RVEF and PLS, LAS is easy to obtain and shows high repeatability. LAS (apex/lateral wall) may provide a more sensitive T2DM-related RV dysfunction index.

Linear late gadolinium enhancement in the basal anterior septum and lateral wall may represent the contrast enhancement of vessels: A CMR and CCTA comparison study.

BACKGROUND: The purpose of this paper was to verify that the linear high-intensity signal on late gadolinium enhancement-cardiac magnetic resonance (LGE-CMR) may represent the contrast enhancement of vessels rather than scars or fibrosis, and to assess whether this linear high-intensity signal will affect the quantification of myocardial fibrosis in patients with hypertrophic cardiomyopathy (HCM). METHODS: A total of 58 patients who underwent both coronary computed tomography angiography (CCTA) and LGE-CMR in our hospital were ultimately enrolled. The definitions of positive linear LGE (LLGE+) were as follows: (1) LLGE in the basal anterior septum or lateral wall, and (2) LLGE observable at 10 mm or more. All other patients were regarded as negative LLGE (LLGE-). In LLGE+ patients, the length of the LLGE located in the anterior septum and lateral wall was compared with the length of the septal perforator artery and the circumflex artery on CCTA, respectively. For nine patients with HCM, the LGE% was measured before and after removal of LLGE. RESULTS: Among the 58 patients, 40 showed LLGE+ and 18 showed LLGE-. For patients with LLGE in the anterior septum, there was a strong correlation between LLGE and anterior septal perforator arteries in length (r=0.887, p<0.001). For patients with LLGE in the lateral wall, LLGE also correlated well with the circumflex arteries in length (r=0.962, p<0.001). In nine patients with HCM, the LGE% decreased significantly after the removal of LLGE [9.50 (7.70 - 17.35)% vs. 8.80 (6.20 - 15.55)%, p<0.05]. CONCLUSIONS: The LLGE in the anterior septum and lateral wall may represent contrast enhancement of the anterior septal perforator artery and the circumflex artery, respectively. This LLGE may overestimate the extent of myocardial fibrosis in patients with HCM.

Deep learning radiomics for focal liver lesions diagnosis on long-range contrast-enhanced ultrasound and clinical factors.

Background: Routine clinical factors play an important role in the clinical diagnosis of focal liver lesions (FLLs); however, they are rarely used in computer-assisted diagnosis. Therefore, we developed a deep learning (DL) radiomics model, and investigated its effectiveness in diagnosing FLLs using long-range contrast-enhanced ultrasound (CEUS) cines and clinical factors. Methods: Herein, 303 patients with pathologically confirmed FLLs after surgery at three hospitals were retrospectively enrolled and divided into a training cohort (n=203), internal validation (IV) cohort (n=50) from one hospital with the ratio of 4:1, and external validation (EV) cohort (n=50) from the other two hospitals. Four DL radiomics models, namely Four Stream 3D convolutional neural network (FS3DU) (trained with CEUS cines only), FS3DU+A (trained with CEUS cines and alpha fetoprotein), FS3DU+H (trained with CEUS cines and hepatitis), and FS3DU+A+H (trained with CEUS cines, alpha fetoprotein, and hepatitis), were formed based on 3D convolutional neural networks (CNNs). They used approximately 20-s preoperative CEUS cines and/or clinical factors to extract spatiotemporal features for the classification of FLLs and the location of the region of interest. The area under curve of the receiver operating characteristic and diagnosis speed were calculated to evaluate the models in the IV and EV cohorts, and they were compared with those of two radiologists. Two-sided Delong tests were used to calculate the statistical differences between the models and radiologists. Results: FS3DU+A+H, which incorporated CEUS cines, hepatitis, and alpha fetoprotein, achieved the highest area under curve of 0.969 (95% CI: 0.901-1.000) and 0.957 (95% CI: 0.894-1.000) among radiologists and other models in IV and EV cohorts, respectively. A significant difference was observed when comparing FS3DU and radiologist 2 (all P<0.05). The diagnosis speed of all the models was the same (10.76 s per patient), and it was two times faster than those of the radiologists (radiologist 1: 23.74 and 27.75 s; radiologist 2: 25.95 and 29.50 s in IV and EV cohorts, respectively). Conclusions: The proposed DL radiomics demonstrated excellent performance on the benign and malignant diagnosis of FLLs by combining CEUS cines and clinical factors. It could help the individualized characterization of FLLs, and enhance the accuracy of diagnosis in the future.

Targeting hepcidin improves cognitive impairment and reduces iron deposition in a diabetic rat model.

Cognitive impairment is a common complication of type 2 diabetes mellitus (T2DM) that may be related to iron deposition in the brain. Hepcidin is expressed in the brain and has the ability to regulate iron. Therefore, this study explored the role of hepcidin in hippocampal iron deposition and cognitive impairment in T2DM. The effects of a recombinant adeno-associated virus targeting hepcidin (AAV-hepcidin) for hippocampal iron content and cognitive function were investigated in a T2DM rat model induced by streptozotocin and a high-fat diet. Adult male rats (n = 32) were categorized as either C-saline (normal control), M-saline (T2DM), M-blank (AAV-blank + T2DM), or M-hepcidin (AAV-hepcidin + T2DM). Hippocampal iron content was assessed using quantitative susceptibility mapping. Morris water maze (MWM) testing was used to assess the cognitive function. Magnetic resonance imaging indicated that hippocampal susceptibility values were significantly increased bilaterally in T2DM rats compared with controls (P = 0.044, P = 0.043). Compared with the M-blank group, the M-hepcidin group exhibited significantly decreased hippocampal susceptibility values bilaterally (P = 0.007, P = 0.030). Compared with the M-saline group, susceptibility values from left hippocampus in the M-hepcidin group were significantly reduced (P = 0.002). MWM results showed that the performance of T2DM rats was significantly decreased from that of control rats. Compared with the M-saline and M-blank groups, the performance of the M-hepcidin group was significantly increased. These studies demonstrate that T2DM rats developed cognitive impairment and iron deposits in the hippocampus, both of which were improved by AAV-hepcidin administration.

Increased fractal dimension of left ventricular trabeculations is associated with subclinical diastolic dysfunction in patients with type-2 diabetes mellitus.

The aim of this study was to investigate the relationship among left ventricular (LV) concentric hypertrophy, endocardial remodeling, and myocardial deformation in type-2 diabetes mellitus (T2DM). Fifty-three T2DM patients with normotension and 36 healthy controls underwent cardiovascular magnetic resonance imaging to assess for LV concentric hypertrophy (LV myocardial mass index, LVMMi; LVMMi-to-LV end-diastolic volume index ratio, MVR), endocardial remodeling (fractal dimension of trabeculations, FD), and myocardial deformation (global longitudinal, radial and circumferential strain, systolic and diastolic strain rate). When compared with healthy controls, T2DM was associated with LV concentric hypertrophy (LVMMi: T2DM, 52.7 ± 8.9 g/m2; controls, 48.7 ± 8.4 g/m2, p = 0.032; MVR: T2DM, 0.88 ± 0.19 g/mL; controls, 0.77 ± 0.16 g/mL, p = 0.007), endocardial remodeling (max. apical FD: T2DM, 1.265 ± 0.056; controls, 1.233 ± 0.055, p = 0.008; mean apical FD: T2DM, 1.198 ± 0.043; controls, 1.176 ± 0.043, p = 0.020), and subtle diastolic dysfunction (peak longitudinal diastolic strain rate, PDSRL: T2DM, 1.1 ± 0.2/s; controls, 1.2 ± 0.3/s, p = 0.031). In the stepwise multivariable regression model, the MVR was an independent determinant of the maximum apical FD (standardized ß, sß = 0.525, p < 0.001) and mean apical FD (sß = 0.568, p < 0.001). The mean apical FD was an independent determinant of the PDSRL (p = 0.004). LV concentric hypertrophy is an independent determinant of endocardial remodeling, a process that may contribute to subtle LV diastolic dysfunction in T2DM patients.

Blood T1* correction increases accuracy of extracellular volume measurements using 3T cardiovascular magnetic resonance: Comparison of T1 and T1* maps.

The goals were to compare the differences between ECVL (extracellular volume derived from myocardial T1 and blood T1), ECVc (combination of myocardial T1 and blood T1*), and ECVnL (derived from myocardium T1* and blood T1*), and to explore the diagnostic accuracy of these factors for discriminating between controls and patients. The Modified Look-Locker Inversion Recovery sequence was performed in 42 subjects to generate both T1 and T1* maps. Native and post-contrast T1 values for myocardium and blood pool were obtained, and ECVL, ECVc, and ECVnL were then calculated. The global ECVc values were smaller than the ECVL values (0.006, 2.11%, p < 0.001) and larger than the ECVnL values (0.06, 21.6%, p < 0.001) in all participants. The ECVc led to a 4-6% increase in the AUC value and a 24-32% reduction in the sample size to differentiate between the controls and other patients when compared with the ECVL. Blood T1* correction can improve the precision of blood T1 values and can consequently increase the accuracy of the extracellular volume fraction measurement. The ECVc can be used to improve diagnostic accuracy and reduce the sample size required for a clinical study.

Left atrium passive ejection fraction is the most sensitive index of type 2 diabetes mellitus-related cardiac changes.

The aims of this study were to use cardiovascular magnetic resonance (CMR) cine to assess left atrium (LA) and left ventricle (LV) function and structure in normotensive type 2 diabetes mellitus (T2DM) patients and to identify the most sensitive index of those T2DM-related cardiac changes. Fifty T2DM patients with normotension (25 males, age 54.7 ± 8.7 years, duration of diabetes: 7.5 ± 5.1 years) and 35 controls (16 males, age: 52.2 ± 13.2 years) were prospectively enrolled. All patients were scanned using CMR four- and two-chamber long-axis cine to assess LA and LV structure and function. Normotensive T2DM patients were associated with decreased LA total ejection fraction (EF), passive EF and LV end diastolic volume, normal LA active EF and LV myocardial mass and increased LV mass/volume (M/V). LA total EF and passive EF correlated with body mass index, duration of diabetes and M/V. To differentiate between diabetic patients and healthy controls, area under the receiver operating characteristic (ROC) curve (AUC) values were calculated to be 0.763, 0.706, 0.647 and 0.649 for LA passive EF, total EF, LVEDV and M/V, respectively. The addition of LA total EF, LVEDV, M/V and the combination thereof did not significantly improve AUC values in a model containing LA passive EF. Normotensive T2DM patients were associated with LA decreased total ejection fraction, decreased passive EF and LV concentric remodeling. Among these indices, LA passive EF was the most sensitive to T2DM-related LA function changes.

Brain iron deposition in type 2 diabetes mellitus with and without mild cognitive impairment-an in vivo susceptibility mapping study.

This study was performed to investigate iron deposition in the brain of type 2 diabetes mellitus (T2DM) patients using quantitative susceptibility mapping (QSM) and the associated cognitive impairments. Sixty patients diagnosed with T2DM were subjected to neuropsychological tests to determine their cognitive status, and the results were used to subdivide the patients into a T2DM without mild cognitive impairment (MCI) group (n = 30) and a T2DM with MCI group (n = 30). All patients underwent high-resolution susceptibility-weighted imaging, and data processing was performed using SMART (Susceptibility Mapping and Phase Artifacts Removal Toolbox) software. The susceptibility values of the bilateral parietal cortex, frontal white matter, caudate nucleus (CN), putamen (PU), globus pallidus, thalamus, red nucleus, substantia nigra (SN), hippocampus (HP) and dentate nucleus were analyzed and correlated with the neuropsychological cognitive scores. Compared with the normal controls (n = 30), the T2DM without MCI group exhibited significantly increased susceptibility values in the left HP, whereas the T2DM with MCI group showed significantly increased susceptibility values in the bilateral CN, HP, left PU and right SN. Compared with the T2DM without MCI group, the T2DM with MCI group exhibited significantly increased susceptibility values in the right CN, SN and left PU. The susceptibility values for the right CN, SN and left PU were closely correlated with neuropsychological cognitive scores. Our results provide a new relation between T2DM and brain iron deposition and suggested that QSM may be a helpful tool in the detection and evaluation of their cognitive impairment in T2DM.

Assessment of Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance T1 Mapping: Correlation with Left-Ventricular Diastolic Dysfunction and Diabetic Duration.

PURPOSE: To quantify extracellular matrix expansion with the cardiovascular magnetic resonance (CMR) T1 mapping technique and the derived extracellular volume fraction (ECV) in diabetic cardiomyopathy (DbCM) patients and to detect the relationship among ECV, duration of diabetes, and diastolic function. MATERIALS: Thirty-eight patients with diabetic cardiomyopathy (20 males, age 54.6 ± 8.6 years) and thirty-two matched normal controls (15 males, age 51.4 ± 13.6 years) were prospectively enrolled. All of them were scanned by T1 mapping to obtain the native and postcontrast T1 values of myocardium and blood, and ECV was calculated accordingly. All patients also underwent transthoracic echocardiographic tissue Doppler imaging to assess left-ventricular diastolic function. RESULTS: There was a significant difference in ECV between the two groups (DbCMs 30.4 ± 2.9% versus controls 27.1 ± 2.4%, P < 0.001). The duration of diabetes was positively and strongly associated with ECV (R = 0.539, P = 0.0005). There was also a significant difference in ECV (P ≤ 0.001) among four groups (A, controls; B, DbCM patients with duration of diabetes <5 years; C, 5-10 years; and D, >10 years). ECV was negatively associated with LV E'/A' (R = -0.403, P = 0.012). CONCLUSION: CMR T1 mapping can reflect myocardial extracellular matrix expansion in DbCM and can be a powerful technique for the early diagnosis of DbCM.

Assessment of Left Ventricular Structural Remodelling in Patients with Diabetic Cardiomyopathy by Cardiovascular Magnetic Resonance.

Background. Diabetic cardiomyopathy (DCM) is always accompanied with alteration of left ventricular structure and function. The aims of this study were to assess the structural remodelling in patients with DCM by cardiovascular magnetic resonance (CMR) and correlation of structural remodelling with severity of DCM. Methods. Twenty-five patients (53.8 ± 8.8 years, 52.0% males) with DCM and thirty-one normal healthy controls (51.9 ± 13.6 years, 45.2% males) were scanned by CMR cine to assess function and structure of left ventricular. Length of diabetic history and results of cardiac echocardiography (E', A', and E'/A') were also measured. Results. Compared with normal controls group, DCM group was associated with significantly increased ratio of left ventricular mass at end diastole to end-diastolic volume (MVR) (P < 0.05) and no significant difference was in mass at end diastole (P > 0.05). The ratio correlated with both length of diabetic history and echocardiographic Doppler tissue imaging E' (all P < 0.05). Conclusions. CMR can be a powerful technique to assess LV remodelling, and MVR may be considered as an imaging marker to evaluate the severity of LV remodelling in patients with DCM.