Magnetic Resonance T1 Mapping Research Articles

Abstract 11438: Texture Analysis Identifies Differences in Cardiac Magnetic Resonance T1 Maps of Pediatric Heart Transplant Patients with Rejection

Introduction: Graft rejection is a significant contributor to morbidity and mortality in pediatric heart transplant recipients, despite surveillance by endomyocardial biopsy (EMB). Cardiac Magnetic Resonance (CMR) T1 mapping has shown potential for noninvasive diagnosis of rejection. However, variability in normative T1 values across field strengths, vendors, and individual scanners limits the utility of absolute T1 values to diagnose rejection across institutions. Texture analysis is an emerging method for quantifying spatial distribution of relative voxel intensities rather than using the absolute voxel intensities themselves and may serve as an additional method for evaluating T1 maps. Hypothesis: We hypothesized that T1 maps from patients with rejection would exhibit differences in texture features from patients without rejection. Methods: This study included 19 cases from 17 pediatric transplant patients (mean age 11.8 ± 5 year, graft age 5.9 ± 4.7 years, 41% female) who underwent CMR imaging and EMB. 8 short axis slices of breath-held T1 mapping using Modified Look-Locker Inversion (MOLLI) recovery on 1.5T Siemens scanner were obtained. Left ventricular myocardium was semiautomatically segmented from T1 maps, excluding the blood pool and epicardial myocardium. Image texture analysis was performed on a single mid-ventricular slice from each case. Rejection was defined as acute cellular rejection (biopsy grade 1R or higher) or negative biopsy with decreased function requiring treatment. T-test analysis was performed to compare differences in texture analysis between patients with and without rejection. Results: Analysis of T1 maps showed differences (p-value ≤ 0.10) between patients with and without rejection in texture features of energy (0.062 ± 0.012 vs 0.091 ± 0.051), entropy (4.59 ± 0.23 vs 4.23 ± 0.60), and variance (0.031 ± 0.005 vs 0.025 ± 0.009). Discussion: In this small pilot study, texture analysis identified differences in tissue character between patients with and without graft rejection. Evaluation of tissue character via texture analysis may provide an additional method for diagnosis of rejection, given the variability in normative T1 values across institutions.

Abstract 11853: Serum Matrix Metalloproteinase 2 is Associated With Lower Ventricular Stiffness and Suboptimal Outcomes in Children With Single Right Ventricle Physiology Who Are Under Consideration for Stage 3 Palliation

Background: Increased extracellular matrix (ECM) metabolism is associated with poor outcomes in numerous cardiovascular diseases. However, its relationship to outcomes in patients with single right ventricle physiology (SRV) is unknown. The objective of this study was to investigate the association of measures of ECM metabolism to outcomes in SRV patients under consideration for stage 3 palliation (S3P). Methods: SRV patients undergoing routine pre-S3P catheterization were prospectively enrolled. Serum matrix metalloproteinase 2 (MMP-2), cardiac magnetic resonance T1 mapping derived extracellular volume (ECV), and pressure-volume loop derived ventricular stiffness (β) by micro-conductance catheter were collected. Controls were age-matched children undergoing closure of clinically insignificant patent ductus arteriosus. SRV were divided into those who had an optimal outcome or suboptimal outcome (hemodynamic concern causing delay in S3P, length of stay ≥ 14 days, heart transplant or death in first year after S3P). Results: Of 30 patients, 15 had SRV and 15 were controls; 7 SRV patients had suboptimal outcome. Mean age was 4.2 ± 0.7 years. SRV patients with suboptimal outcome had lower β (p = 0.05) and ECV (p = 0.04) than patients with optimal outcome (Figure A and B, respectively). MMP-2 was lower in SRV patients with suboptimal outcome compared to SRV patients with optimal outcome and controls (Figure C) (p = 0.05). In SRV patients, MMP-2 correlated with β (r = 0.56, p = 0.03). Conclusion: In biventricular heart disease characterized by chronically increased afterload, MMP-2, ECV, and ventricular stiffness are elevated. In contrast, this study shows that SRV patients with lower MMP-2, ECV, and ventricular stiffness have worse outcomes at the time of S3P; this suggests immature ECM metabolism leads to poor outcomes in SRV patients. Future studies exploring the mechanism by which immature ECM and dysregulated ECM metabolism influence SRV outcomes are warranted.

PEF-treated plant and animal tissues: Insights by approaching with different electroporation assessment methods

The goal of our investigation was to explore the level of membrane permeabilization in plant and animal food matrices (potato, apple, chicken) as resulting from subjecting these matrices to pulsed electric field treatment whereby we employed different assessment methods (electrical impedance spectroscopy, current-voltage measurements, magnetic resonance imaging). Our study was performed using a number of amplitudes of eight electric pulses of 100 μs in duration, and results were expressed in terms of the change in electrical properties as evaluated by electrical impedance spectroscopy, current-voltage measurements, and changes in the water (re)distribution as evaluated by magnetic resonance imaging and T2 mapping techniques. The findings of our research provide useful insights and could be in support of an appropriate choice of electroporation assessment methods in relation to the food matrix characteristics, and for the determination and selection of appropriate PEF treatment conditions.

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

BackgroundTo 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. MethodsTwenty-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. ResultsThe 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). ConclusionsStress T1 response strongly correlates with pathological MVD and CVF, indicating that stress CMR T1 mapping can accurately detect microvascular dysfunction.

Improving the robustness of MOLLI T1 maps with a dedicated motion correction algorithm

Myocardial tissue T1 constitutes a reliable indicator of several heart diseases related to extracellular changes (e.g. edema, fibrosis) as well as fat, iron and amyloid content. Magnetic resonance (MR) T1-mapping is typically achieved by pixel-wise exponential fitting of a series of inversion or saturation recovery measurements. Good anatomical alignment between these measurements is essential for accurate T1 estimation. Motion correction is recommended to improve alignment. However, in the case of inversion recovery sequences, this correction is compromised by the intrinsic contrast variation between frames. A model-based, non-rigid motion correction method for MOLLI series was implemented and validated on a large database of cardiac clinical cases (n = 186). The method relies on a dedicated similarity metric that accounts for the intensity changes caused by T1 magnetization relaxation. The results were compared to uncorrected series and to the standard motion correction included in the scanner. To automate the quantitative analysis of results, a custom data alignment metric was defined. Qualitative evaluation was performed on a subset of cases to confirm the validity of the new metric. Motion correction caused noticeable (i.e. > 5%) performance degradation in 12% of cases with the standard method, compared to 0.3% with the new dedicated method. The average alignment quality was 85% ± 9% with the default correction and 90% ± 7% with the new method. The results of the qualitative evaluation were found to correlate with the quantitative metric. In conclusion, a dedicated motion correction method for T1 mapping MOLLI series has been evaluated on a large database of clinical cardiac MR cases, confirming its increased robustness with respect to the standard method implemented in the scanner.

Reduction of extracellular volume and reverse cardiac remodeling during sacubitril/valsartan therapy assessed by cardiac magnetic resonance in patients with heart failure (REMODELING CMR-HF)

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf REMODELING HF Background/Introduction: Extracellular volume (ECV) expansion is a major determinant of cardiac remodeling in heart failure. Cardiac magnetic resonance (CMR) T1 mapping has been developed as a noninvasive technique to estimate ECV. Purpose The objective of this study is to assess the response to Sacubitril/Valsartan by measuring changes in myocardial ECV and their association with reverse cardiac remodeling in patients with heart failure with reduced ejection fraction (HFrEF). Methods Prospective, single-center, open-label study of two hundred-four HFrEF patients underwent CMR T1 mapping using the modified Look-Locker inversion recovery (MOLLI) sequence for ECV calculation, and initiated with sacubitril-valsartan treatment according to Guideline-Directed Medical Therapy. Absolute change in myocardial ECV, serum levels of procollagen type I amino-terminal peptide (PINP) and procollagen type III amino-terminal peptide (PIIINP), left ventricular end-diastolic volume index, left ventricular end-systolic volume index and left ventricle ejection fraction (LVEF) were analyzed from baseline to 12-month follow-up. Results Baseline MOLLI-ECV was 48.2% ± 2.4 in 106 patients with ischemic cardiomyopathy (ICM) and 38.7% ± 2.7 in 98 with idiopathic dilated cardiomyopathy (DCM), decreasing to 34% ± 2.4 for ICM and 29.5% ± 2.7 for DCM (P &amp;lt; 0.001), at 12 months with sacubitril-valsartan therapy. These changes were correlated with a reduction of -36 μg/L for PINP (CI 95% 78-93, P &amp;lt; 0.001), and -3.0 μg/L for PIIINP (CI 95% 73-91, P &amp;lt; 0.001), -20 ml/m² in left ventricle end-diastolic and -18 ml/m² in end-systolic volumes, and an improvement in LVEF from 29% to 36% in both groups (P &amp;lt; 0.001). Conclusions For the first time, we observe that changes in extracellular volume induced by sacubitril-valsartan therapy are related to reverse cardiac remodeling in patients with in HFrEF. These findings suggest that there may be an opportunity to decrease adverse remodeling with the use of a CMR-guided therapeutic approach aimed at decreasing fibrogenic activity and modulate the remodeling process.

Evaluation of liver function in patients with chronic hepatitis B using Gd-EOB-DTPA-enhanced T1 mapping at different acquisition time points: a feasibility study.

This study aimed to explore the impact of different acquisition times on the evaluation of liver function levels in chronic hepatitis B using Gd-EOB-DTPA-enhanced T1 positioning technology under 3.0 Tesla magnetic resonance imaging (MRI). A total of 146 patients with chronic hepatitis B (CHB) were classified into four groups as follows: chronic hepatitis B without liver cirrhosis (CH, 22 cases), liver cirrhosis with Child-Pugh classification A (LCA 63 cases), Child-Pugh B (LCB 47 cases) and Child-Pugh C (LCC 14 cases). Normal liver function (NLF) group was composed of 23 persons who had healthy liver and no medical histories of hepatitis. T1 mapping images were performed before and after administration of Gd-EOB-DPTA using Look-Locker sequence. Changes in T1 relaxation time (T1rt), the reduction rate of T1 relaxation time (ΔT1) and the increase in T1 relaxation rate (ΔR1) of liver over time (at 5, 10, 15 and 20min) were investigated and compared among all five groups using a one-way analysis of variance (ANOVA). The Spearman's rank correlation coefficient (r) was used to show the correlations of these parameters in different liver function groups. In the NLF, CH, LCA and LCB groups, postT1 gradually decreased, while the ΔT1 and ΔR1 gradually increased with time. The parameters were compared between different liver function levels at the same time point, and the differences were statistically significant except for NLF-CH, NLF-LCA and CH-LCA. There was no significant difference in the area under the ROC curve of other parameters at 10, 15 and 20min. At each time point, no correlation was found between preT1rt and the degrees of liver function. PostT1rt was positively correlated with liver function classification, while ΔT1 and ΔR1 were negatively correlated with liver function classification. Gd-EOB-DTPA-enhanced T1 mapping magnetic resonance imaging is beneficial to assess liver function. Using the Gd-EOB-DTPA to enhance T1 mapping imaging to assess liver function can shorten the observation time of the hepatobiliary period and 10min after enhancement may be the best time point.

Management of immune checkpoint inhibitor myocarditis: a serial cardiovascular magnetic resonance T2 mapping approach.

Management of immune checkpoint inhibitor myocarditis: a serial cardiovascular magnetic resonance T2 mapping approach.

Maturation process of regenerated tissues after single-stage simultaneous autologous particulated cartilage implantation and open wedge high tibial osteotomy for articular cartilage defects with medial osteoarthritis of bilateral knees: a case report

BackgroundOpen wedge high tibial osteotomy (OWHTO) is an effective treatment option for young and middle-aged active patients with medial unicompartmental knee osteoarthritis (OA). In addition, particulated cartilage implantation has been developed as a simple procedure for cartilage regeneration. Thus, to improve the OWHTO outcomes, a single-stage, simultaneous bilateral knee arthroscopic particulated cartilage implantation with OWHTO was performed.Case presentationA 60-year-old male patient presented with severe bilateral knee pain, with grade 2 varus knee OA of the Kellgren–Lawrence classification. Primary arthroscopic evaluations based on the International Cartilage Repair Society grading system showed grade 3c articular cartilage defects of 1.5 cm in diameter at the center of the bilateral medial femoral condyles. Following bilateral OWHTO, the healthy cartilage tissue was harvested from the lateral wall of the unilateral femoral intercondylar notch and minced with the cartilage processor. Then, subchondral drillings and cartilage fragment implantations into the bilateral defects were performed arthroscopically. One year postsurgery, second-look arthroscopy findings revealed that the defects were filled with cartilage-like tissues. The maturation process of the regenerated tissues was confirmed with T2 mapping magnetic resonance imaging during the 3-year follow-up period. The patient could walk without a cane, and all Knee Injury and Osteoarthritis Outcome Score parameters were improved without any correction loss in 3 years.ConclusionsThis is the first report to evaluate the maturation process of the implanted particulated cartilage tissue with T2 mapping magnetic resonance imaging for 3 years. The effect of chondral resurfacing procedure with OWHTO remains unclear; however, the implantation of arthroscopic particulated cartilage fragments is a single-stage and less-invasive procedure. This treatment could regenerate cartilage-like tissue in the present case. Therefore, this additional procedure could potentially improve the long-term outcomes of OWHTO.

T2-mapping MRI evaluation of patellofemoral cartilage in patients submitted to intra-articular platelet-rich plasma (PRP) injections

This study evaluated the ability of T2 mapping magnetic resonance imaging at 3 T, in addition to morphological sequences, to assess efficacy of platelet-rich plasma (PRP) injections, characterizing qualitatively and quantitatively the grade of knee cartilage repair in patients with patellofemoral chondropathy. We retrospectively studied 34 patients (22 men, 12 women, mean age 41.8 years, including 22 men) with patellofemoral knee chondropathy, who underwent intra-articular PRP injections and completed a clinical and instrumental follow-up. As control group, we evaluated 34 patients who underwent non-operative therapy. All patients were submitted to clinical (using VAS and WOMAC index) and imaging studies with 3 T magnetic resonance with cartilage analysis with T2 mapping sequences for cartilage analysis before and after treatment. In the study group, mean pre-treatment T2 relaxation time values were 44.2 ± 2.5 ms, considering all articular cartilage compartments, with significant reduction at the follow-up (p < 0.001). At the index compartment, mean pre-treatment T2 relaxation times values were 47.8 ± 3.6 ms, with statistically significant reduction at the follow-up (p < 0.001). Evaluation of focal cartilage lesions reported pre-treatment mean T2 value of 70.1 ± 13.0 ms and post-treatment mean value of 59.9 ± 4.6 ms (p < 0.001). From a clinical point of view, the pre-treatment WOMAC and VAS scores were 18.3 ± 4.5 and 7 (IQR:6–7.2), respectively; the post-treatment values were 7.3 ± 3.2 and 2 (IQR: 1.7–3.0), respectively (p < 0.001). In the control group, despite clinical improvement, we didn’t find significant T2 values change during the follow-up period. In conclusion, T2 mapping is a valuable indicator for chondropathy and treatment-related changes over time.

MR T1 mapping for quantifying brain manganese deposition in type C hepatic encephalopathy rats.

To evaluate magnetic resonance (MR) T1 mapping for quantifying brain manganese (Mn) deposition in type C hepatic encephalopathy (CHE) rats and to investigate the mechanism of magnesium sulfate (MgSO4) therapy. Thirty Sprague-Dawley rats were randomly assigned into normal control group (NC, n = 6) and CHE groups (n = 24). Thioacetamide (TAA) was used for modeling CHE rats. CHE groups were further divided into 4 subgroups: TAA group, MgSO4 low dose (Mg-L) group, MgSO4 high dose (Mg-H) group and deionized water (DW) group (n = 6 for each group). TAA, Mg-L, Mg-H and DW groups were received intraperitoneal injections of 250mg TAA/kg, twice a week for 8weeks. Mg-L and Mg-H groups were orally received MgSO4 of 124 and 248mg/kg daily, respectively, for another 8weeks (without TAA). MR T1 mapping was performed in NC, TAA, Mg-L, Mg-H and DW groups at various time points. T1 value and Mn content in basal ganglia, hippocampus, cerebral cortex and cerebellum were evaluated. Morris water maze (MWM) and narrow beat test (NBT) were utilized to evaluate rats' learning, memory and motor ability. Contents of interleukin-6 (IL-6), tumor necrosis factor-a (TNF-a) and calcium-binding adaptor 1 protein (Iba1) were evaluated. Reduced T1 values in basal ganglia, hippocampus and cerebral cortex (P < 0.01, P < 0.05 and P < 0.05, respectively); increased Mn content in basal ganglia, hippocampus and cerebral cortex (all P < 0.05); reduced times of head contacting with region of interest (ROI), reduced times of entrance into the target quadrant (both P < 0.05); increased NBT total time (P < 0.05); increased brain contents of IL-6 (P < 0.001), TNF-α (P < 0.01) and over-expression of Iba1 were found in TAA group compared to NC group. After treated by MgSO4, increased T1 value and reduced Mn content in basal ganglia, hippocampus and cerebral cortex (all P < 0.01); increased times of head contacting with ROI, increased times of entrance into the target quadrant (both P < 0.05); reduced NBT total time (P < 0.01); reduced brain content of IL-6, TNF-α (both P < 0.05) and reduced expression of Iba1 were found. T1 values were negatively correlated with Mn contents in basal ganglia (r = - 0.834, P < 0.01), hippocampus (r = - 0.739, P < 0.05), cortex (r = - 0.801, P < 0.05) and cerebellum (r = - 0.788, P < 0.05). T1 mapping could quantify brain Mn deposition in CHE rats. MgSO4 could improve cognition and motor ability of CHE rats by reducing brain Mn deposition, alleviating neurological inflammation and achieve the effective therapy for CHE. Mn may participate in the pathogenesis of CHE through neuroinflammation.

Evaluation of Pancreatic Fibrosis Grading by Multiparametric Quantitative Magnetic Resonance Imaging.

Early detection and grading of pancreatic fibrosis (PF) are important and challenging clinical goals. To determine main pancreatic duct (MPD) diameter, pancreatic thickness, and grades of PF via magnetic resonance elastography (MRE), T1 mapping, and intravoxel incoherent motion diffusion-weighted imaging (IVIM-DWI), assessing respective diagnostic performances. Prospective. Histopathologic and imaging records (MRE, T1 mapping, and IVIM-DWI) generated by 144 patients between December 2018 and May 2020 were collected for analysis. Grades of PF were distributed as follows: F0, 82; F1, 22; F2, 22; and F3, 18. 3 T pancreatic MRI, encompassing MRE, T1 mapping, and IVIM-DWI. In all patients, T1 relaxation times, pancreatic stiffness values, IVIM-DWI parameters, MPD diameter, and pancreatic thickness were measured. Receiver operating characteristic (ROC) analysis served to assess imaging parameters useful in diagnosing PF. To identify relations between specific parameters and grades of PF, logistic regression analysis was invoked. Both pancreatic stiffness (r=0.754; P < 0.001) and T1 relaxation time (r=0.433; P < 0.001) correlated significantly with PF (%). To determine PF grades ≥F1, a combined model (area under the curve [AUC]=0.906) performed significantly better than pancreatic stiffness (AUC=0.855; P < 0.001) or T1 relaxation time (AUC=0.754; P < 0.001) alone. For PF grades ≥F2 or grade F3, both the combined model (≥F2: AUC=0.910; F3: AUC=0.939) and pancreatic stiffness (≥F2: AUC=0.906; F3: AUC=0.929) outperformed T1 relaxation time (≥F2: AUC=0.768 [P=0.005 and P=0.004, respectively]; F3: AUC=0.816 [both P < 0.005]). All IVIM-DWI parameters generated AUC values <0.700. A combination of MRE and T1 mapping seems promising in diagnosing various grades of PF, particularly at an early stage. 1 TECHNICAL EFFICACY: Stage 2.

Diffuse myocardial fibrosis by T1 mapping is associated with heart failure in pediatric primary dilated cardiomyopathy

BackgroundIn adult cardiomyopathy (CM), diffuse myocardial fibrosis is associated with adverse clinical outcome. However, its relevance in pediatric patients remains relatively unknown. The study aimed to evaluate myocardial extracellular volume (ECV) reflecting diffuse myocardial fibrosis with cardiovascular magnetic resonance (CMR) T1 mapping, and to analyze correlations with clinical and functional data in children and adolescents with different CM phenotypes. MethodsPatients with primary dilated (DCM), hypertrophic (HCM) or left ventricular non-compaction CM (LVNC) were prospectively enrolled and compared with healthy controls. Study participants underwent standardized CMR with modified Look-Locker Inversion recovery (MOLLI) T1 mapping. ResultsIn total, 33 patients (median age 12.0 years; DCM: n = 10, HCM: n = 13; LVNC: n = 10) and 7 controls (14.5 years) were included.DCM: ECV was higher than in controls (38.1 ± 7.5% vs. 27.2 ± 3.6%; p = 0.014). Patients with elevated ECV were younger than those with normal values (p = 0.044). ECV correlated with N-terminal pro brain natriuretic peptide (r = 0.66, p = 0.038), left ventricular ejection fraction (r = −0.63, p = 0.053), and stroke volume of left (r = −0.75, p = 0.013) and right ventricle (r = −0.67, p = 0.033). During a median follow-up of 25.3 months, 3 patients underwent heart transplantation (HTx), and 2 were listed for HTx. All 5 patients had elevated ECV.HCM/LVNC: ECV was within normal range in HCM (25.5 ± 4.5%) and LVNC (29.6 ± 4.2), and was not related with clinical and/or functional parameters. ConclusionsOur results indicate an increased burden of diffuse myocardial fibrosis in relation with younger age in pediatric DCM. ECV was associated with clinical and biventricular functional markers of heart failure in DCM.

Non-invasive Assessment of Subclinical Renal Parenchymal Changes in Chronic Hepatitis B Virus By T1 Mapping Magnetic Resonance Imaging.

Background:Renal parenchymal changes are seen in chronic hepatitis B virus (HBV) infection, and its disease diagnosis should be confirmed by renal biopsy, which is an invasive technique. Apparent-T1 mapping magnetic resonance imaging (MRI) is an established imaging technique that assesses subclinical tissue injury without using a contrast agent.Aims:To investigate the early stage subclinical renal changes without apparent renal dysfunction in patients with chronic HBV infection by renal apparent-T1 mapping MRI.Study Design:A cross-sectional study.Methods:This study included 45 participants with normal kidney function, wherein 25 have biopsy-proven chronic HBV hepatitis and 20 are healthy individuals. Liver and kidney biochemical tests were performed within 1 month before the MRI scan, and the estimated glomerular filtration rate was calculated by diet modification in renal disease formula. Breath-hold, electrocardiogram-gated Modified Look-Locker Imaging sequence was acquired in the coronal plane without contrast agent administration. Apparent-T1 mapping value was measured by manually drawing a region of interest in six points for both kidneys by two observers. Apparent-T1 mapping values were compared between the two groups.Results:The mean apparent-T1 mapping values of the kidneys were significantly higher in patients with chronic HBV infection compared to the control group (1445 ± 129 ms vs. 1306 ± 115 ms, P = 0.003). Inter-class correlation coefficient measurement analysis showed excellent agreement.Conclusion:Renal apparent-T1 mapping MRI may help show the early stage of renal parenchymal disease without apparent renal dysfunction in chronic HBV infection.

Arginine Metabolites as Biomarkers of Myocardial Ischaemia, Assessed with Cardiac Magnetic Resonance Imaging in Chronic Kidney Disease.

(1) Background: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with chronic kidney disease (CKD). Myocardial oxygenation and perfusion response to stress, using oxygen-sensitive cardiovascular magnetic resonance (OS-CMR) and stress T1 mapping respectively, are impaired in CKD patients with and without known coronary artery disease (CAD). Endothelial dysfunction, assessed by circulating levels of asymmetric dimethylarginine (ADMA) and homoarginine (HMA), promotes atherosclerosis. We hypothesized that in CKD patients, worsening endothelial dysfunction is associated with worsening myocardial oxygenation and perfusion as assessed by change in OS-CMR signal intensity (Δ OS-CMR SI) and stress T1 (ΔT1) values. (2) Methods: 38 patients with advanced CKD underwent cardiovascular magnetic resonance (CMR) scanning at 3 Tesla. OS-CMR and T1 mapping images were acquired both at rest and after adenosine stress and analyzed semi-quantitatively. Serum ADMA and HMA concentrations were assessed using mass spectrometry. (3) Results: There was no significant correlation between Δ OS-CMR SI and ADMA or HMA. Interestingly, there was a significant negative correlation seen between Δ T1 and ADMA (r = −0.419, p = 0.037, n = 30) but not between Δ T1 and HMA. (4) Conclusions: Stress T1 response is impaired in CKD patients and is independently associated with higher circulating ADMA concentrations.

Technical Note: Fully automatic segmental relaxometry (FASTR) for cardiac magnetic resonance T1 mapping.

Cardiac relaxometry techniques, particularly T1 mapping, have recently gained clinical importance in various cardiac pathologies. Myocardial T1 and extracellular volume are usually calculated from manual identification of left ventricular epicardial and endocardial regions. This is a laborious process, particularly for large volume studies. Here we present a fully automated relaxometry framework (FASTR) for segmental analysis of T1 maps (both native and postcontrast) and partition coefficient (λ). Patients (N=11) were imaged postacute myocardial infarction on a 1.5T clinical scanner. The scan protocol involved CINE-SSFP imaging, native, and post-contrast T1 mapping using the Modified Look-Locker Inversion (MOLLI) recovery sequence. FASTR consisted of automatic myocardial segmentation of spatio-temporally coregistered CINE images as an initial guess, followed by refinement of the contours on the T1 maps to derive segmental T1 and λ. T1 and λ were then compared to those obtained from two trained expert observers. Robust endocardial and epicardial contours were achieved on T1 maps despite the presence of infarcted tissue. Relative to experts, FASTR resulted in myocardial Dice coefficients (native T1: 0.752±0.041; postcontrast T1: 0.751±0.057) that were comparable to interobserver Dice (native T1: 0.803±0.045; postcontrast T1: 0.799±0.054). There were strong correlations observed for T1 and λ derived from experts and FASTR (native T1: r=0.83; postcontrast T1: r=0.87; λ: r=0.78; P<0.0001), which were comparable to inter-expert correlation coefficients (native T1: r=0.90; postcontrast T1: r=0.93; λ: r=0.80; P<0.0001). Our fully automated framework, FASTR, can generate accurate myocardial segmentations for native and postcontrast MOLLI T1 analysis without the need for manual intervention. Such a design is appealing for high volume clinical protocols.

Deep neural network ensemble for on-the-fly quality control-driven segmentation of cardiac MRI T1 mapping.

Recent developments in artificial intelligence have generated increasing interest to deploy automated image analysis for diagnostic imaging and large-scale clinical applications. However, inaccuracy from automated methods could lead to incorrect conclusions, diagnoses or even harm to patients. Manual inspection for potential inaccuracies is labor-intensive and time-consuming, hampering progress towards fast and accurate clinical reporting in high volumes. To promote reliable fully-automated image analysis, we propose a quality control-driven (QCD) segmentation framework. It is an ensemble of neural networks that integrate image analysis and quality control. The novelty of this framework is the selection of the most optimal segmentation based on predicted segmentation accuracy, on-the-fly. Additionally, this framework visualizes segmentation agreement to provide traceability of the quality control process. In this work, we demonstrated the utility of the framework in cardiovascular magnetic resonance T1-mapping - a quantitative technique for myocardial tissue characterization. The framework achieved near-perfect agreement with expert image analysts in estimating myocardial T1 value (r=0.987,p<.0005; mean absolute error (MAE)=11.3ms), with accurate segmentation quality prediction (Dice coefficient prediction MAE=0.0339) and classification (accuracy=0.99), and a fast average processing time of 0.39 second/image. In summary, the QCD framework can generate high-throughput automated image analysis with speed and accuracy that is highly desirable for large-scale clinical applications.

Molecular Mechanisms of Adenosine Stress T1 Mapping.

Adenosine stress T1 mapping is an emerging magnetic resonance imaging method to investigate coronary vascular function and myocardial ischemia without application of a contrast agent. Using gene-modified mice and 2 vasodilators, we elucidated and compared the mechanisms of adenosine myocardial perfusion imaging and adenosine T1 mapping. Wild-type (WT), A2AAR-/- (adenosine A2A receptor knockout), A2BAR-/- (adenosine A2B receptor knockout), A3AR-/- (adenosine A3 receptor knockout), and eNOS-/- (endothelial nitric oxide synthase knockout) mice underwent rest and stress perfusion magnetic resonance imaging (n=8) and T1 mapping (n=10) using either adenosine, regadenoson (a selective A2AAR agonist), or saline. Myocardial blood flow and T1 were computed from perfusion imaging and T1 mapping, respectively, at rest and stress to assess myocardial perfusion reserve and T1 reactivity (ΔT1). Changes in heart rate for each stress agent were also calculated. Two-way ANOVA was used to detect differences in each parameter between the different groups of mice. Myocardial perfusion reserve was significantly reduced only in A2AAR-/- compared to WT mice using adenosine (1.06±0.16 versus 2.03±0.52, P<0.05) and regadenoson (0.98±026 versus 2.13±0.75, P<0.05). In contrast, adenosine ΔT1 was reduced compared with WT mice (3.88±1.58) in both A2AAR-/- (1.63±1.32, P<0.05) and A2BAR-/- (1.55±1.35, P<0.05). Furthermore, adenosine ΔT1 was halved in eNOS-/- (1.76±1.46, P<0.05) versus WT mice. Regadenoson ΔT1 was approximately half of adenosine ΔT1 in WT mice (1.97±1.50, P<0.05), and additionally, it was significantly reduced in eNOS-/- mice (-0.22±1.46, P<0.05). Lastly, changes in heart rate was 2× greater using regadenoson versus adenosine in all groups except A2AAR-/-, where heart rate remained constant. The major findings are that (1) although adenosine myocardial perfusion reserve is mediated through the A2A receptor, adenosine ΔT1 is mediated through the A2A and A2B receptors, (2) adenosine myocardial perfusion reserve is endothelial independent while adenosine ΔT1 is partially endothelial dependent, and (3) ΔT1 mediated through the A2A receptor is endothelial dependent while ΔT1 mediated through the A2B receptor is endothelial independent.

Ultrahigh-field cardiovascular magnetic resonance T1 and T2 mapping for the assessment of anthracycline-induced cardiotoxicity in rat models: validation against histopathologic changes

BackgroundChemotherapy-induced cardiotoxicity is a well-recognized adverse effect of chemotherapy. Quantitative T1-mapping cardiovascular magnetic resonance (CMR) is useful for detecting subclinical myocardial changes in anthracycline-induced cardiotoxicity. The aim of the present study was to histopathologically validate the T1 and T2 mapping parameters for the evaluation of diffuse myocardial changes in rat models of cardiotoxicity.MethodsRat models of cardiotoxicity were generated by injecting rats with doxorubicin (1 mg/kg, twice a week). CMR was performed with a 9.4 T ultrahigh-field scanner using cine, pre-T1, post-T1 and T2 mapping sequences to evaluate the left ventricular ejection fraction (LVEF), native T1, T2, and extracellular volume fraction (ECV). Histopathological examinations were performed and the association of histopathological changes with CMR parameters was assessed.ResultsFive control rats and 36 doxorubicin-treated rats were included and classified into treatment periods. In the doxorubicin-treated rats, the LVEF significantly decreased after 12 weeks of treatment (control vs. 12-week treated: 73 ± 4% vs. 59 ± 9%, P = 0.01). Increased native T1 and ECV were observed after 6 weeks of treatment (control vs. 6-week treated: 1148 ± 58 ms, 14.3 ± 1% vs. 1320 ± 56 ms, 20.3 ± 3%; P = 0.005, < 0.05, respectively). T2 values also increased by six weeks of treatment (control vs. 6-week treated: 16.3 ± 2 ms vs. 10.3 ± 1 ms, P < 0.05). The main histopathological features were myocardial injury, interstitial fibrosis, inflammation, and edema. The mean vacuolar change (%), fibrosis (%), and inflammation score were significantly higher in 6-week treated rats than in the controls (P = 0.03, 0.03, 0.02, respectively). In the univariable analysis, vacuolar change showed the highest correlation with native T1 value (R = 0.60, P < 0.001), and fibrosis showed the highest correlation with ECV value (R = 0.78, P < 0.001). In the multiple linear regression analysis model, vacuolar change was a significant factor for change in native T1 (P = 0.01), and vacuolar change and fibrosis were significant factors for change in ECV (P = 0.006, P < 0.001, respectively) by adding other histopathological parameters (i.e., inflammation and edema scores)ConclusionsQuantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.

Myocardial T1 and T2 Mapping by Magnetic Resonance in Patients With Immune Checkpoint Inhibitor–Associated Myocarditis

BackgroundMyocarditis is a potentially fatal complication of immune checkpoint inhibitor (ICI) therapy. Data on the utility of cardiovascular magnetic resonance (CMR) T1 and T2 mapping in ICI myocarditis are limited. ObjectivesThis study sought to assess the value of CMR T1 and T2 mapping in patients with ICI myocarditis. MethodsIn this retrospective study from an international registry of patients with ICI myocarditis, clinical and CMR findings (including T1 and T2 maps) were collected. Abnormal T1 and T2 were defined as 2 SD above site (vendor/field strength specific) reference values and a z-score was calculated for each patient. Major adverse cardiovascular events (MACE) were a composite of cardiovascular death, cardiogenic shock, cardiac arrest, and complete heart block. ResultsOf 136 patients with ICI myocarditis with a CMR, 86 (63%) had T1 maps and 79 (58%) also had T2 maps. Among the 86 patients (66.3 ± 13.1 years of age), 36 (41.9%) had a left ventricular ejection fraction <55%. Across all patients, mean z-scores for T1 and T2 values were 2.9 ± 1.9 (p < 0.001) and 2.2 ± 2.1 (p < 0.001), respectively. On Siemens 1.5-T scanner (n = 67), native T1 (1,079.0 ± 55.5 ms vs. 1,000.3 ± 22.1 ms; p < 0.001) and T2 (56.2 ± 4.9 ms vs. 49.8 ± 2.2 ms; p < 0.001) values were elevated compared with reference values. Abnormal T1 and T2 values were seen in 78% and 43% of the patients, respectively. Applying the modified Lake Louise Criteria, 95% met the nonischemic myocardial injury criteria and 53% met the myocardial edema criteria. Native T1 values had excellent discriminatory value for subsequent MACE, with an area under the curve of 0.91 (95% confidence interval: 0.84 to 0.98). Native T1 values (for every 1-unit increase in z-score, hazard ratio: 1.44; 95% confidence interval: 1.12 to 1.84; p = 0.004) but not T2 values were independently associated with subsequent MACE. ConclusionsThe use of T1 mapping and application of the modified Lake Louise Criteria provides important diagnostic value, and T1 mapping provides prognostic value in patients with ICI myocarditis.