Fully automated pixel-wise quantitative CMR-myocardial perfusion with CMR-coronary angiography to detect hemodynamically significant coronary artery disease.

OBJECTIVES: We applied a fully automated pixel-wise post-processing framework to evaluate fully quantitative cardiovascular magnetic resonance myocardial perfusion imaging (CMR-MPI). In addition, we aimed to evaluate the additive value of coronary magnetic resonance angiography (CMRA) to the diagnostic performance of fully automated pixel-wise quantitative CMR-MPI for detecting hemodynamically significant coronary artery disease (CAD). METHODS: A total of 109 patients with suspected CAD were prospectively enrolled and underwent stress and rest CMR-MPI, CMRA, invasive coronary angiography (ICA), and fractional flow reserve (FFR). CMRA was acquired between stress and rest CMR-MPI acquisition, without any additional contrast agent. Finally, CMR-MPI quantification was analyzed by a fully automated pixel-wise post-processing framework. RESULTS: Of the 109 patients, 42 patients had hemodynamically significant CAD (FFR ≤ 0.80 or luminal stenosis ≥ 90% on ICA) and 67 patients had hemodynamically non-significant CAD (FFR ˃ 0.80 or luminal stenosis < 30% on ICA) were enrolled. On the per-territory analysis, patients with hemodynamically significant CAD had higher myocardial blood flow (MBF) at rest, lower MBF under stress, and lower myocardial perfusion reserve (MPR) than patients with hemodynamically non-significant CAD (p < 0.001). The area under the receiver operating characteristic curve of MPR (0.93) was significantly larger than those of stress and rest MBF, visual assessment of CMR-MPI, and CMRA (p < 0.05), but similar to that of the integration of CMR-MPI with CMRA (0.90). CONCLUSIONS: Fully automated pixel-wise quantitative CMR-MPI can accurately detect hemodynamically significant CAD, but the integration of CMRA obtained between stress and rest CMR-MPI acquisition did not provide significantly additive value. KEY POINTS: • Full quantification of stress and rest cardiovascular magnetic resonance myocardial perfusion imaging can be postprocessed fully automatically, generating pixel-wise myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) maps. • Fully quantitative MPR provided higher diagnostic performance for detecting hemodynamically significant coronary artery disease, compared with stress and rest MBF, qualitative assessment, and coronary magnetic resonance angiography (CMRA). • The integration of CMRA and MPR did not significantly improve the diagnostic performance of MPR alone.

[Water migration and kinetics of Arecae Semen during moistening process].

In this study, low-field nuclear magnetic resonance(LF-NMR) and magnetic resonance imaging(MRI) were employed to analyze the water distribution, status, and migration in the moistening process of Arecae Semen. Peleg model was adopted to study the water absorption kinetics of Arecae Semen moistened at different water temperatures(10, 30, and 50 ℃). The Arecae Semen samples soaked at different water temperatures all contained four water states: binding water T_(21), non-flowing water T_(22), free water T_(23), and unbound water T_(24). Non-flowing water had the largest increase in peak area during the moistening process, followed by free water. The peak areas of non-flowing water, free water, and total water were correlated with the water content(P<0.01). Therefore, LF-NMR can quickly and non-destructively predict the water content of Arecae Semen during moistening. The peak area of non-flowing water and the content of free water were correlated with the content of arecoline in the soaking solution(P<0.01), which indicated that the faster flow of non-flowing water and more free water corresponded to more arecoline dissolved. The MRI images showed that the water migration pathway varied at different soaking temperatures, and the moistening degree obtained by this means was consistent with that obtained based on traditional experience. The rate constant K_1 fitted by Peleg model decreased with the increase in water temperature, while the capacity constant K_2 showed an opposite trend. The Arrhenius equation fitting of K_1 with temperature showed that the activation energy of Arecae Semen in the moistening process was 32.98 kJ·mol~(-1). LF-NMR/MRI can be used to analyze the water status and content and determine the end moisturing point of Arecae Semen. Peleg model can accurately describe the water absorption properties of Arecae Semen in the moistening process. The findings of this study can guide the moistening optimization and mechanism research of other seed Chinese medicinal materials.

Diagnostic Utility of the Simplified Perfusion Fraction for Identifying Myocardial Injury in Patients With Reperfused ST-segment Elevation Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is a disease with high morbidity and mortality worldwide and the evaluation of myocardial injury and perfusion status following myocardial ischemia and reperfusion is of clinical value. PURPOSE: To assess the diagnostic utility of simplified perfusion fraction (SPF) in differentiating salvage and infarcted myocardium and its predictive value for left ventricular remodeling in patients with reperfusion ST-segment elevation myocardial infarction (STEMI). STUDY TYPE: Prospective. POPULATION: Forty-one reperfused STEMI patients and 20 healthy volunteers. FIELD STRENGTH/SEQUENCE: 3.0T MRI. The MR examination included cine, T2 -short tau inversion recovery (T2 -STIR), first pass perfusiong (FPP)，phase sensitive inversion recovery (PSIR), and diffusion-weighted imaging (DWI). ASSESSMENT: SPF values among different myocardium regions (infarcted, salvaged, remote, and MVO) and stages of reperfused STEMI patients as well as normal controls were measured. The diagnostic utility of SPF values in differentiating salvaged and infarcted myocardium was assessed. STATISTICAL ANALYSIS: Independent t-test and the Mann-Whitney U-test. Logistic regression. RESULTS: SPF values in healthy controls were not significantly different than SPF values in the remote myocardium of patients (40.09 ± 1.47% vs. 40.28 ± 1.93%, P = 0.698). In reperfusion STEMI patients, SPF values were lower in infarcted myocardium compared to remote and salvaged myocardium (32.15 ± 2.36% vs. 40.28 ± 1.93%, P < 0.001; 32.15 ± 2.36% vs. 36.68 ± 2.71%, P < 0.001). SPF values of infarcted myocardium showed a rebound increase from acute to convalescent stages (32.15 ± 2.36% vs. 34.69 ± 3.69%, P < 0.001). When differentiating infarcted and salvaged myocardium, SPF values demonstrated an area under the curve (AUC) of 0.89 (sensitivity 85.4%, specificity 80.5%, cutoff 34.42%). Lower SPF values were associated with lower odds ratio (OR = 0.304) of left ventricular remodeling after adjusting for potential confounders with a confidence interval (CI) of 0.129-0.717, P = 0.007. DATA CONCLUSION: SPF might be able to differentiate salvaged and infarcted myocardium and is a strong predictor of left ventricular remodeling in reperfused STEMI patients. Level of Evidence 2 Technical Efficacy Stage 2.

Systemic ventricular strain and torsion are predictive of elevated serum NT-proBNP in Fontan patients: a magnetic resonance study.

BACKGROUND: This study aimed to investigate the associations between cardiac strain, cardiac torsion, ventricular volumes, and ventricular ejection fraction, with N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in Fontan patients who were age- and gender-matched with healthy control subjects. METHODS: Cardiovascular magnetic resonance (CMR) studies performed in 22 (15 male, 7 female) patients with single-ventricle physiology (all morphological left ventricles) palliated with Fontan and 17 (10 male, 7 female) age- and gender-matched healthy children volunteers were retrospectively analyzed. Serum NT-proBNP levels were obtained in Fontan subjects. Standard post-processing of CMR images included systemic ventricular end-diastolic and end-systolic volumes, stroke volume, cardiac mass, atrioventricular regurgitation, and ejection fraction. CMR tissue tracking (TT) software was used to quantify global longitudinal strain (GLS), global radial strain (GRS), and global circumferential strain (GCS) and torsion of the systemic ventricle. Pearson and Spearman correlation coefficients were used in comparisons of correlations between NT-proBNP and functional parameters in repair Fontan patients. Intra-observer and inter-observer variability of CMR strain and torsion values were determined from 10 randomly selected Fontan subjects and 10 randomly selected control subjects. RESULTS: GLS was significantly lower in Fontan patients than in control subjects (-15.19±2.94 vs. -19.97±1.70; P<0.001). GLS was not significantly different between normal NT-proBNP levels and high NT-proBNP levels in Fontan patients (-15.59±2.72 vs. -14.62±3.32; P=0.462). The GCS of repair Fontan patients was not significantly lower than that of the control group (-16.76±3.27 vs. -17.88±2.26; P=0.235). GCS was significantly different between normal and high NT-proBNP levels group in Fontan patients (-17.95±2.43 vs. -15.04±3.67; P=0.036). The peak systolic torsion and peak systolic torsion rates were significantly lower in Fontan patients than in control subjects (0.81±0.41 vs. 1.07±0.36, P=0.044; 7.36±3.41 vs. 9.85±2.61, P=0.017). Peak systolic torsion was significantly lower in Fontan patients with normal NT-proBNP levels than in high NT-proBNP subjects (0.67±0.43 vs. 1.01±0.29; P=0.036). GCS and torsion were more strongly correlated with NT-proBNP in the patient group (r=0.541 for GCS; r=0.588 for torsion, P<0.01). The parameters of strain and torsion could be reproduced with sufficient accuracy by intra-observer agreement(biases =0.04 for GLS; biases =0.66 for GCS; biases =1.03 for GRS; biases =0.04 for torsion) and inter-observer agreement (biases =0.32 for GLS; biases =0.85 for GCS; biases =1.52 for GRS; biases =0.18 for torsion). CONCLUSIONS: GLS is an earlier marker of contractile dysfunction in repair Fontan patients. Peak systolic torsion may be a biomarker for determining subclinical dysfunction, as it is more strongly correlated with serum biomarkers of ventricular function than ventricular size or ejection fraction.

Different Myocardial Perfusion Status in Acute Myocardial Infarction and Infarct-like Myocarditis: A Novel Intravoxel Incoherent Motion Diffusion-weighted Imaging based MRI Study.

PURPOSE: The following study evaluated the diagnostic value of myocardial perfusion in patients with acute myocardial infarction (AMI) and "infarct-like myocarditis" using Intravoxel Incoherent Motion-Diffusion Weighted Imaging (IVIM-DWI imaging). METHOD: CMR data from 20 patients with suspected AMI, 20 patients with "infarct-like myocarditis" and 20 volunteers were retrospectively analyzed. IVIM-DWI data were acquired using multi-b value single-shot spin-echo echo-planar imaging sequence. IVIM-DWI data were generated according to the 16-segments AHA-model. Cine sequences covering left and right ventricle in short axis and three long axis were analyzed using a dedicated tissue-tracking algorithm. RESULTS: Overall, the AMI T2+ segments exhibited decreased apparent diffusion coefficient (ADC), ADCslow, ADC fast and f values (1.39 ± 0.23 µm2/ms, 1.36 ± 0.23 µm2/ms, 70.77 ± 7.04 µm2/ms, and 0.1243 ± 0.01, respectively) compared to infarct-like myocarditis T2+ (1.48 ± 0.11 µm2/ms, 1.44 ± 0.11 µm2/ms, 87.66 ± 12.50 µm2/ms, and 0.1411 ± 0.02, respectively) and normal controls (1.55 ± 0.07 µm2/ms, 1.52 ± 0.06 µm2/ms, 108.84 ± 4.06 µm2/ms, and 0.1599 ± 0.01, respectively) (all p < 0.05). In addition, AMI LGE+ segments showed significantly lower IVIM-DWI associated parameters (1.34 ± 0.21 µm2/ms, 1.31 ± 0.21 µm2/ms, 68.75 ± 6.33µm2/ms, and 0.1198 ± 0.01) compared to infarct-like myocarditis LGE+ (1.42 ± 0.06 µm2/ms, 1.38 ± 0.08 µm2/ms, 79.12 ± 5.70 µm2/ms, and 0.1313 ± 0.02) (p < 0.05). Moreover, left ventricular peak subendo and subepi radial, circumferential, and longitudinal strain were lower in AMI T2+ segments than in infarct-like myocarditis T2+ segments and normal controls (p < 0.05); AMI LGE+ segments exhibited the lowest strain in three orientations compared to other subgroups (p < 0.05). CONCLUSION: These findings prove that IVIM-DWI may be used as a reliable sequence for evaluation of different myocardial perfusion patterns in AMI and infarct-like myocarditis. AMI may exhibit lower myocardial perfusion status compared to infarct-like myocarditis due to different pathophysiological process.

Histogram Analysis of Native T1 Mapping and Its Relationship to Left Ventricular Late Gadolinium Enhancement, Hypertrophy, and Segmental Myocardial Mechanics in Patients With Hypertrophic Cardiomyopathy.

BACKGROUND: The use of native T1 mapping for evaluation of hypertrophic cardiomyopathy (HCM) is being explored, and its combination with histogram analysis may benefit the accuracy of such assessments. PURPOSE: To investigate the relationship of segmental left ventricular wall thickness (LVWT), myocardial fibrosis, and strain parameters with segmental histogram parameters of native T1 mapping in HCM patients. STUDY TYPE: Retrospective. SUBJECTS: Ninety-three HCM patients without previous cardiovascular diseases were included. FIELD STRENGTH/SEQUENCE: 3.0T cardiac MR. Steady-state free precession cine imaging, modified Look-Locker inversion recovery, phase-sensitive inversion recovery. ASSESSMENT: Images were assessed by three experienced radiologists. STATISTICAL TESTS: Mann-Whitney U-tests, area under the curve (AUC), Spearman's rank correlation, intraclass correlation coefficient, and Bland-Altman test were used for statistical analysis. RESULTS: A higher LVWT value correlated with higher means, minimums, 10th /25th /50th /75th /90th percentiles, maximums, kurtosis, entropy, and lower SD and energy of T1 mapping (P < 0.05 for all), with the correlation being stronger for entropy and energy (Spearman's rho = 0.439 and -0.413, respectively) than other parameters. Late gadolinium enhancement positive (LGE+) segments exhibited higher mean, minimum, 10th /25th /50th /75th /90th percentiles, maximum, entropy, and lower energy of T1 times than late gadolinium enhancement negative (LGE-) segments (P < 0.001 for all). Impaired strain function parameters (peak thickening and thickening rate in radial, circumferential, and longitudinal directions) demonstrated a weak correlation with higher entropy (P < 0.001 for all) and lower energy (P < 0.001 for all). DATA CONCLUSION: Histogram parameters of native T1 mapping provide more information than mean T1 times alone. Among these parameters, entropy and energy may correlate better with LVWT, myocardial late gadolinium enhancement, and strain parameters than mean T1 times in HCM patients. LEVEL OF EVIDENCE: 2 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;49:668-677.

General control non-repressible 20 (GCN20) functions in root growth by modulating DNA damage repair in Arabidopsis.

BACKGROUND: Most ABC transporters are engaged in transport of various compounds, but its subfamily F lacks transmembrane domain essential for chemical transportation. Thus the function of subfamily F remains further elusive. RESULTS: Here, we identified General Control Non-Repressible 20 (GCN20), a member of subfamily F, as new factor for DNA damage repair in root growth. While gcn20-1 mutant had a short primary root with reduced meristem size and cell number, similar primary root lengths were assayed in both wild-type and GCN20::GCN20 gcn20-1 plants, indicating the involvement of GCN20 in root elongation. Further experiments with EdU incorporation and comet assay demonstrated that gcn20-1 displays increased cell cycle arrest at G2/M checkpoint and accumulates more damaged DNA. This is possible due to impaired ability of DNA repair in gcn20-1 since gcn20-1 seedlings are hypersensitive to DNA damage inducers MMC and MMS compared with the wild type plants. This note was further supported by the observation that gcn20-1 is more sensitive than the wild type when subjected to UV treatment in term of changes of both fresh weight and survival rate. CONCLUSIONS: Our study indicates that GCN20 functions in primary root growth by modulating DNA damage repair in Arabidopsis. Our study will be useful to understand the functions of non-transporter ABC proteins in plant growth.

Myocardial fibrosis evaluated by diffusion-weighted imaging and its relationship to 3D contractile function in patients with hypertrophic cardiomyopathy.

BACKGROUND: Previous studies have shown that diffusion-weighted imaging (DWI) is sensitive to myocardial fibrosis in ischemic and nonischemic cardiomyopathy. PURPOSE: To explore the prognostic value of apparent diffusion coefficient (ADC) for detecting myocardial fibrosis and its relationship to the contractile function in hypertrophic cardiomyopathy (HCM). STUDY TYPE: Prospective. POPULATION: A total of 45 HCM patients and 20 controls. FIELD STRENGTH/SEQUENCE: 3.0T cardiac MRI. The cardiac MR sequences included cine, T1 mapping, and DWI. ASSESSMENT: According to the presence of late gadolinium enhancement (LGE) and the extracellular volume (ECV) values (+2 SD of control subjects), respectively, reader W and reader J assessed the value of ADC of each segment for detecting myocardial fibrosis and its relationship to impaired contractile function in HCM patients. STATISTICAL TESTS: Independent sample t-test, Pearson analysis, and intraclass correlation (ICC). RESULTS: The value of ECV was 23.6 ± 3.0% for control. ECV ≥ 29.6% and ECV < 29.6% groups were classified. ADC values in the ECV ≥ 29.6% group were significantly increased compared to the ECV < 29.6% group, (2.41 ± 0.23 µm2 /ms vs. 2.03 ± 0.16 µm2 /ms, P < 0.005). Compared to the LGE - group, ECV (32.1 ± 2.3% vs. 29.0 ± 2.8%, P < 0.005) and ADC (2.60 ± 0.18 µm2 /ms vs. 2.10 ± 0.07 µm2 /ms, P < 0.005) values were significantly increased in the LGE + group. ADC values were linearly associated with ECV values (R2 = 0.65) in HCM patients. ADC values were linearly associated with circumferential and longitudinal strain (R2 = 0.60, R2 = 0.46), as well as circumferential, longitudinal, and radial strain rate (R2 = 0.13, R2 = 0.25, R2 = 0.17, respectively). DATA CONCLUSION: Contractile dysfunction in HCM is predominantly associated with ADC, which is a feasible alternative to ECV and LGE for detecting myocardial fibrosis. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1139-1146.

CATALASE2 functions for seedling postgerminative growth by scavenging H2 O2 and stimulating ACX2/3 activity in Arabidopsis.

Increased fatty acid ß-oxidation is essential for early postgerminative growth in seedlings, but high levels of H2 O2 produced by ß-oxidation can induce oxidative stress. Whether and how catalase (CAT) functions in fine-tuning H2 O2 homeostasis during seedling growth remain unclear. Here, we report that CAT2 functions in early seedling growth. Compared to the wild type, the cat2-1 mutant, with elevated H2 O2 levels, exhibited reduced root elongation on sucrose (Suc)-free medium, mimicking soils without exogenous sugar supply. Treatment with the H2 O2 scavenger potassium iodide rescued the mutant phenotype of cat2-1. In contrast to the wild type, the cat2-1 mutant was insensitive to the CAT inhibitor 3-amino-1,2,4-triazole in terms of root elongation when grown on Suc-free medium, suggesting that CAT2 modulates early seedling growth by altering H2 O2 accumulation. Furthermore, like cat2-1, the acyl-CoA oxidase (ACX) double mutant acx2-1 acx3-6 showed repressed root elongation, suggesting that CAT2 functions in early seedling growth by regulating ACX activity, as this activity was inhibited in cat2-1. Indeed, decreased ACX activity and short root of cat2-1 seedlings grown on Suc-free medium were rescued by overexpressing ACX3. Together, these findings suggest that CAT2 functions in early seedling growth by scavenging H2 O2 and stimulating ACX2/3 activity.

Overexpression of Rat Neurons Nitric Oxide Synthase in Rice Enhances Drought and Salt Tolerance.

Nitric oxide (NO) has been shown to play an important role in the plant response to biotic and abiotic stresses in Arabidopsis mutants with lower or higher levels of endogenous NO. The exogenous application of NO donors or scavengers has also suggested an important role for NO in plant defense against environmental stress. In this study, rice plants under drought and high salinity conditions showed increased nitric oxide synthase (NOS) activity and NO levels. Overexpression of rat neuronal NO synthase (nNOS) in rice increased both NOS activity and NO accumulation, resulting in improved tolerance of the transgenic plants to both drought and salt stresses. nNOS-overexpressing plants exhibited stronger water-holding capability, higher proline accumulation, less lipid peroxidation and reduced electrolyte leakage under drought and salt conditions than wild rice. Moreover, nNOS-overexpressing plants accumulated less H2O2, due to the observed up-regulation of OsCATA, OsCATB and OsPOX1. In agreement, the activities of CAT and POX were higher in transgenic rice than wild type. Additionally, the expression of six tested stress-responsive genes including OsDREB2A, OsDREB2B, OsSNAC1, OsSNAC2, OsLEA3 and OsRD29A, in nNOS-overexpressing plants was higher than that in the wild type under drought and high salinity conditions. Taken together, our results suggest that nNOS overexpression suppresses the stress-enhanced electrolyte leakage, lipid peroxidation and H2O2 accumulation, and promotes proline accumulation and the expression of stress-responsive genes under stress conditions, thereby promoting increased tolerance to drought and salt stresses.

Salt stress reduces root meristem size by nitric oxide-mediated modulation of auxin accumulation and signaling in Arabidopsis.

The development of the plant root system is highly plastic, which allows the plant to adapt to various environmental stresses. Salt stress inhibits root elongation by reducing the size of the root meristem. However, the mechanism underlying this process remains unclear. In this study, we explored whether and how auxin and nitric oxide (NO) are involved in salt-mediated inhibition of root meristem growth in Arabidopsis (Arabidopsis thaliana) using physiological, pharmacological, and genetic approaches. We found that salt stress significantly reduced root meristem size by down-regulating the expression of PINFORMED (PIN) genes, thereby reducing auxin levels. In addition, salt stress promoted AUXIN RESISTANT3 (AXR3)/INDOLE-3-ACETIC ACID17 (IAA17) stabilization, which repressed auxin signaling during this process. Furthermore, salt stress stimulated NO accumulation, whereas blocking NO production with the inhibitor N(ω)-nitro-l-arginine-methylester compromised the salt-mediated reduction of root meristem size, PIN down-regulation, and stabilization of AXR3/IAA17, indicating that NO is involved in salt-mediated inhibition of root meristem growth. Taken together, these findings suggest that salt stress inhibits root meristem growth by repressing PIN expression (thereby reducing auxin levels) and stabilizing IAA17 (thereby repressing auxin signaling) via increasing NO levels.