Coronary Microvascular Dysfunction and Diffuse Myocardial Fibrosis in Patients With Type 2 Diabetes Using Quantitative Perfusion MRI.

BACKGROUND: Imaging techniques that quantitatively and automatically measure changes in the myocardial microcirculation in patients with diabetes are lacking. PURPOSE: To detect diabetic myocardial microvascular complications using a novel automatic quantitative perfusion MRI technique, and to explore the relationship between myocardial microcirculation dysfunction and fibrosis. STUDY TYPE: Prospective. SUBJECTS: 101 patients with type 2 diabetes mellitus (T2DM) (53 without and 48 with complications), 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T; modified Look-Locker inversion-recovery sequence; saturation recovery sequence and dual-bolus technique; segmented fast low-angle shot sequence. ASSESSMENT: All participants underwent MRI to determine the rest myocardial blood flow (MBF), stress MBF, myocardial perfusion reserve (MPR), and extracellular volume (ECV), which represents the extent of myocardial fibrosis. STATISTICAL TESTS: Kolmogorov-Smirnov test, Shapiro-Wilk test, Kruskal-Wallis H test, Mann-Whitney U test, chi-square test, Spearman correlation coefficient, multivariable linear regression analysis. P < 0.05 was considered statistically significant. RESULTS: The rest MBF was not significantly different between the T2DM without complications group (1.1, IQR: 0.9-1.3) and the control group (1.1, 1.0-1.3) (P = 1.000), but it was significantly lower in the T2DM with complications group (0.8, 0.6-1.0) than in both other groups. The stress MBF and MPR were significantly lower in the T2DM without complications group (1.9, 1.5-2.3, and 1.7, 1.4-2.1, respectively) than in the control group (3.0, 2.6-3.5, and 2.7, 2.4-3.1, respectively), and were also significantly lower in the T2DM with complications group (1.1, 0.9-1.4, and 1.4, 1.2-1.8, respectively) than in the T2DM without complications group. A decrease in MBF and MPR were significantly associated with an increase in the ECV. DATA CONCLUSION: Quantitative perfusion MRI can evaluate myocardial microcirculation dysfunction. In T2DM, there was a significant decrease in both MBF and MPR compared to healthy controls, with the decrease being significantly different between T2DM with and without complications groups. The decrease of MBF was significantly associated with the development of myocardial fibrosis, as determined by ECV. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Assessment of Myocardial Viability and Risk Stratification in Coronary Chronic Total Occlusion: A Qualitative and Quantitative Stress Cardiac MRI Study.

BACKGROUND: Indicators for assessing myocardial viability and risk stratification in patients with coronary chronic total occlusion (CTO) are still in the research stage. PURPOSE: To use stress-MRI to assess myocardial function, blood perfusion, and viability and to explore their relationship with collateral circulation. STUDY TYPE: Prospective. SUBJECTS: Fifty-one patients with CTO in at least one major artery confirmed by X-ray coronary angiography (male: 46; age 55.2 ± 10.8 years). FIELD STRENGTH/SEQUENCE: 3.0T; TurboFlash, balanced steady-state free precession cine, and phase-sensitive inversion recovery sequences. ASSESSMENT: Stress-MRI was used to obtain qualitative and quantitative parameters of segmental myocardium. Myocardial segments supplied by CTO target vessels were grouped according to the degree of collateral circulation assessed by radiographic coronary angiography (no/mild, moderate, or good). Depending on qualitative stress perfusion assessment and late gadolinium enhancement (LGE) extent, segments were also categorized as negative, viable, or trans-infarcted. STATISTICAL TESTS: Independent sample Student's t-test, one-way analysis of variance (ANOVA) test, Mann-Whitney U test, Kruskal-Wallis test, Spearman correlation coefficient (r). P < 0.05 was considered statistically significant. RESULTS: A total of 334 segments were supplied by CTO target vessels. The radial strain (RS), circumferential strain (CS), longitudinal strain (LS) of the negative, viable, and trans-infarcted regions showed a significant and stepwise impairment. Myocardial blood flow at rest was positively correlated with RS, CS, and LS (r = 0.42, 0.43, 0.38, respectively). Among the different collateral circulation, there were no significant differences in RS, CS, LS, and LGE volume (P = 0.788, 0.562, 0.122, 0.170, respectively), and there were also no statistically significant differences in the proportions of negative, viable, and trans-infarcted regions (P = 0.372). DATA CONCLUSION: Myocardial perfusion obtained by stress-MRI combined with strain and LGE may comprehensively evaluate myocardial function and viability, and has potential to facilitate risk stratification of CTO. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Comparative analysis of the autism­related variants between different autistic children in a family pedigree.

The present study aimed to provide evidence for the genetic heterogeneity of familial autism spectrum disorder (ASD), which might help to improve our understanding of the complex polygenic basis of this disease. Whole­exome sequencing (WES) was performed on two autistic children in a family pedigree, and reasonable conditions were set for preliminarily screening variant annotations. Sanger sequencing was used to verify the preliminarily screened variants and to determine the possible sources. In addition, autism­related genes were screened according to autism databases, and their variants were compared between two autistic children. The results showed that there were 21 genes respectively for autistic children â…£2 and â…£4, preliminarily screened from all variants based on the harmfulness (high) and quality (high or medium) of the variants, as well as the association between mutant genes and autism in human gene mutation database. Furthermore, candidate autism­related genes were screened according to the evidence score of >4 in the Autism KnowledgeBase (AutismKB) database or ≥3 in the AutDB database. A total of 11 and 10 candidate autism­related genes were identified in the autistic children â…£2 and Ⅳ4, respectively. Candidate genes with an evidence score of >16 in AutismKB were credible autism­related genes, which included LAMC3, JMJD1C and CACNA1H in child Ⅳ2, as well as SCN1A, SETD5, CHD7 and KCNMA1 in child â…£4. Other than the c.G1499A mutation of SCN1A, which is known to be associated with Dravet syndrome, the specific missense variant loci of other six highly credible putative autism­related genes were reported for the first time, to the best of the authors' knowledge, in the present study. These credible autism­related variants were inherited not only from immediate family members but also from extended family members. In summary, the present study established a reasonable and feasible method for screening credible autism­related genes from WES results, which by be worth extending into clinical practice. The different credible autism­related genes between the two autistic children indicated a complex polygenic architecture of ASD, which may assist in the early diagnosis of this disease.

Evaluation of isolated left ventricular noncompaction using cardiac magnetic resonance tissue tracking in global, regional and layer-specific strains.

We used cardiac magnetic resonance tissue tracking (CMR-TT) to quantitatively analyze the global, regional and layer-specific strain of isolated left ventricular noncompaction (ILVNC). Combined with late gadolinium enhancement (LGE), we initially explored the effect of focal myocardial fibrosis on myocardial strain. CMR was performed in 63 patients with ILVNC and 52 patients without ILVNC (i.e., the control group). The ILVNC group was divided into an LGE(+) group (29 patients) and an LGE(-) group (34 patients) according to the presence or absence of late gadalinum enhancement (LGE). CVI42 software was used to measure global and regional (basal, middle, apical) radial strain (RS), circumferential strain (CS), longitudinal strain (LS), subendocardial LS and subepicardial LS. The basal-apical strain gradient was defined as the apical mean strain minus the basal mean strain. We then compared differences between these strain parameters. The subendocardial-subepicardial LS gradient was defined as the maximum subendocardial LS minus the subepicardial LS. Compared with the control group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the ILVNC group were significantly diminished (P < 0.01). Compared with the LGE(-) group, the global and regional RS, CS, LS and the subendocardial, subepicardial LS of the LGE(+) group were significantly diminished (P < 0.05). In the ILVNC group, the basal-apical CS and LS gradient, and the subendocardial-subepicardial LS gradient were significantly lower than those in the control group (P < 0.01). There were significant differences in myocardial strain between patients with and without ILVNC. ILVNC revealed a specific pattern in terms of strain change. The myocardial strain of the cardiac apex and endocardium was significantly lower than that of the cardiac base and epicardium, respectively. Myocardial strain reduction was more significant in ILVNC patients with focal myocardial fibrosis.