Cardiac magnetic resonance (CMR) imaging is widely used in various medical fields related to cardiovascular diseases. Rapid technological innovations in magnetic resonance imaging in recent times ...have resulted in the development of new techniques for CMR imaging. T1 and T2 image mapping sequences enable the direct quantification of T1, T2, and extracellular volume fraction (ECV) values of the myocardium, leading to the progressive integration of these sequences into routine CMR settings. Currently, T1, T2, and ECV values are being recognized as not only robust biomarkers for diagnosis of cardiomyopathies, but also predictive factors for treatment monitoring and prognosis. In this study, we have reviewed various T1 and T2 mapping sequence techniques and their clinical applications.
Cardiac diffusion weighted-magnetic resonance imaging (DWI) has slowly developed due to its technical difficulties. However, this limitation could be overcome by advanced techniques, including a ...stimulated echo technique and a gradient moment nulling technique. This study aimed to develop and validate a high-order DWI sequence, using echo-planar imaging (EPI) and second-order motion-compensated (M012) diffusion gradient applied to cardiac imaging in small-sized animals with fast heart and respiratory rates, and to investigate the feasibility of cardiac DWI, diagnosing acute myocardial injury in isoproterenol-induced myocardial injury rat models. The M012 diffusion gradient sequence was designed for diffusion tensor imaging of the rat myocardium and validated in the polyvinylpyrrolidone phantom. Following sequence optimization, 23 rats with isoproterenol-induced acute myocardial injury and five healthy control rats underwent cardiac MRI, including cine imaging, T1 mapping, and DWI. Diffusion gradient was applied using a 9.4-T MRI scanner (Bruker, BioSpec 94/20, gradient amplitude = 440 mT/m, maximum slew rate = 3440 T/m/s) with double gating (electrocardiogram and respiratory gating). Troponin I was used as a serum biomarker for myocardial injury. Histopathologic examination of the heart was subsequently performed. The developed DWI sequence using EPI and M012 provided the interpretable images of rat hearts. The apparent diffusion coefficient (ADC) values were significantly higher in rats with acute myocardial injury than in the control group (1.847 ± 0.326 * 10
mm
/s vs. 1.578 ± 0.144 * 10
mm
/s, P < 0.001). Troponin I levels were increased in the blood samples of rats with acute myocardial injury (P < 0.001). Histopathologic examinations detected myocardial damage and subendocardial fibrosis in rats with acute myocardial injury. The newly developed DWI technique has the ability to detect myocardial injury in small animal models, representing high ADC values on the myocardium with isoproterenol-induced injury.
Chemotherapy-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.
Rat 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.
Five 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) CONCLUSIONS: Quantitative T1 and T2 mapping CMR is a useful non-invasive tool reflecting subclinical histopathological changes in anthracycline-induced cardiotoxicity.
A reliable, non-invasive diagnostic method is needed for early detection and serial monitoring of cardiotoxicity, a well-known side effect of chemotherapy. This study aimed to assess the feasibility ...of T1-mapping cardiac magnetic resonance imaging (CMR) for evaluating subclinical myocardial changes in a doxorubicin-induced cardiotoxicity rabbit model. Adult male New Zealand White rabbits were injected twice-weekly with doxorubicin and subjected to CMR on a clinical 3T MR system before and every 2-4 weeks post-drug administration. Native T1 and extracellular volume (ECV) values were measured at six mid-left ventricle (LV) and specific LV lesions. Histological assessments evaluated myocardial injury and fibrosis. Three pre-model and 11 post-model animals were included. Myocardial injury was observed from 3 weeks. Mean LV myocardium ECV values increased significantly from week 3 before LV ejection fraction decreases (week 6), and ECVs of the RV upper/lower insertion sites and papillary muscle exceeded those of the LV. The mean native T1 value in the mid-LV increased significantly increased from week 6, and LV myocardium ECV correlated strongly with the degree of fibrosis (r = 0.979, p < 0.001). Myocardial T1 mapping, particularly ECV values, reliably and non-invasively detected early cardiotoxicity, allowing serial monitoring of chemotherapy-induced cardiotoxicity.
Objective The purpose of this study was to evaluate the magnetic resonance (MR) characteristics and applicability of new, uniform, extremely small iron-based nanoparticles (ESIONs) with 3–4-nm iron ...cores using contrast-enhanced magnetic resonance angiography (MRA). Materials and Methods Seven types of ESIONs were used in phantom and animal experiments with 1.5T, 3T, and 4.7T scanners. The MR characteristics of the ESIONs were evaluated via phantom experiments. With the ESIONs selected by the phantom experiments, animal experiments were performed on eight rabbits. In the animal experiments, the in vivo kinetics and enhancement effect of the ESIONs were evaluated using half-diluted and non-diluted ESIONs. The between-group differences were assessed using a linear mixed model. A commercially available gadolinium-based contrast agent (GBCA) was used as a control. Results All ESIONs showed a good T1 shortening effect and were applicable for MRA at 1.5T and 3T. The relaxivity ratio of the ESIONs increased with increasing magnetic field strength. In the animal experiments, the ESIONs showed peak signal intensity on the first-pass images and persistent vascular enhancement until 90 minutes. On the 1-week follow-up images, the ESIONs were nearly washed out from the vascular structures and organs. The peak signal intensity on the first-pass images showed no significant difference between the non-diluted ESIONs with 3-mm iron cores and GBCA (p = 1.000). On the 10-minutes post-contrast images, the non-diluted ESIONs showed a significantly higher signal intensity than did the GBCA (p Conclusion In the phantom experiments, the ESIONs with 3–4-nm iron oxide cores showed a good T1 shortening effect at 1.5T and 3T. In the animal experiments, the ESIONs with 3-nm iron cores showed comparable enhancement on the first-pass images and superior enhancement effect on the delayed images compared to the commercially available GBCA at 3T.
Right ventricular (RV) free wall fibrosis is an important component of adverse remodeling with RV dysfunction in pulmonary hypertension (PH). However, no previous reports have compared cardiovascular ...magnetic resonance (CMR) findings and histological analysis for RV free wall fibrosis in PH. We aimed to assess the feasibility of CMR T1 mapping with extracellular volume fraction (ECV) for evaluating the progression of RV free wall fibrosis in PH, and compared imaging findings to histological collagen density through an animal study.
Among 42 6-week-old Wistar male rats, 30 were classified according to disease duration (baseline before monocrotaline injection, and 2, 4, 6 and 8 weeks after injection) and 12 were used to control for aging (4 and 8 weeks after the baseline). We obtained pre and post-contrast T1 maps for native T1 and ECV of RV and left ventricular (LV) free wall for six animals in each disease-duration group. Collagen density of RV free wall was calculated with Masson's trichrome staining. The Kruskall-Wallis test was performed to compare the groups. Native T1 and ECV to collagen density were analyzed with Spearman's correlation.
The mean values of native T1, ECV and collagen density of the RV free wall at baseline were 1541 ± 33 ms, 17.2 ± 1.3%, and 4.7 ± 0.5%, respectively. The values of RV free wall did not differ according to aging (P = 0.244, 0.504 and 0.331, respectively). However, the values significantly increased according to disease duration (P < 0.001 for all). Significant correlations were observed between native T1 and collagen density (r = 0.770, P < 0.001), and between ECV and collagen density for the RV free wall (r = 0.815, P < 0.001) in PH. However, there was no significant difference in native T1 and ECV values for the LV free wall according to the disease duration from the baseline (P = 0.349 and 0.240, respectively).
We observed significantly increased values for native T1 and ECV of the RV free wall without significant increase of the LV free wall according to the disease duration of PH, and findings were well correlated with histological collagen density.
Purpose To evaluate the effect of changes in hematocrit level on myocardial extracellular volume (ECV) fraction, as quantified with cardiac magnetic resonance (MR) imaging in an animal model. ...Materials and Methods Thirteen adult male Sprague-Dawley rats underwent cardiac MR imaging before and after induction of anemia. MR imaging procedures, including unenhanced and contrast material-enhanced T1 mapping, were performed by using a saturation recovery Look-Locker sequence with a 9.4-T unit. An optimized T1 mapping sequence was established in the phantom study. Systolic function of the left ventricle (LV) was calculated from the cine images. Native and postcontrast T1 values of the LV myocardium at the midcavity level and LV blood pool, partition coefficients, and ECV were calculated. Histopathologic examination of the heart was performed after sacrifice. Intergroup comparison of variables was performed with the paired t test. Results The postanemia models exhibited lower hematocrit levels, postcontrast T1 values of the LV pool, and partition coefficients (mean, 45.7% ± 5.2 standard deviation; 563.8 msec ± 155.7; and 29.2 ± 3.5, respectively) than did the preanemia models (mean, 59.0% ± 4.1; 690.2 msec ± 109.7; and 38.2 ± 4.4, respectively) (P < .05 for all comparisons). There were no differences between the pre- and postanemia groups in terms of LV ejection fraction (mean, 72.7% ± 2.1 vs 73.2% ± 4.7; P = .78) and ECV (mean, 15.5% ± 2.0 vs 16.0% ± 1.9; P = .24). Conclusion Myocardial ECV measured with contrast-enhanced T1 mapping cardiac MR imaging did not significantly change despite changes in hematocrit level in anemic rat models. Extrapolation of this finding from animal models to human subjects suggests that ECV measured with MR imaging could be a robust parameter in anemic patients.
Objective: The purpose of this study was to evaluate the magnetic resonance (MR) characteristics and applicability of new, uniform, extremely small iron-based nanoparticles (ESIONs) with 3-4-nm iron ...cores using contrast-enhanced magnetic resonance angiography (MRA). Materials and Methods: Seven types of ESIONs were used in phantom and animal experiments with 1.5T, 3T, and 4.7T scanners. The MR characteristics of the ESIONs were evaluated via phantom experiments. With the ESIONs selected by the phantom experiments, animal experiments were performed on eight rabbits. In the animal experiments, the in vivo kinetics and enhancement effect of the ESIONs were evaluated using half-diluted and non-diluted ESIONs. The between-group differences were assessed using a linear mixed model. A commercially available gadolinium-based contrast agent (GBCA) was used as a control. Results: All ESIONs showed a good T1 shortening effect and were applicable for MRA at 1.5T and 3T. The relaxivity ratio of the ESIONs increased with increasing magnetic field strength. In the animal experiments, the ESIONs showed peak signal intensity on the first-pass images and persistent vascular enhancement until 90 minutes. On the 1-week follow-up images, the ESIONs were nearly washed out from the vascular structures and organs. The peak signal intensity on the first-pass images showed no significant difference between the non-diluted ESIONs with 3-mm iron cores and GBCA (p = 1.000). On the 10-minutes post-contrast images, the non-diluted ESIONs showed a significantly higher signal intensity than did the GBCA (p < 0.001). Conclusion: In the phantom experiments, the ESIONs with 3-4-nm iron oxide cores showed a good T1 shortening effect at 1.5T and 3T. In the animal experiments, the ESIONs with 3-nm iron cores showed comparable enhancement on the first-pass images and superior enhancement effect on the delayed images compared to the commercially available GBCA at 3T.
Objective: T1 mapping provides valuable information regarding cardiomyopathies. Manual drawing is time consuming and prone to subjective errors. Therefore, this study aimed to test a DL algorithm for ...the automated measurement of native T1 and extracellular volume (ECV) fractions in cardiac magnetic resonance (CMR) imaging with a temporally separated dataset. Materials and Methods: CMR images obtained for 95 participants (mean age ± standard deviation, 54.5 ± 15.2 years), including 36 left ventricular hypertrophy (12 hypertrophic cardiomyopathy, 12 Fabry disease, and 12 amyloidosis), 32 dilated cardiomyopathy, and 27 healthy volunteers, were included. A commercial deep learning (DL) algorithm based on 2D U-net (Myomics-T1 software, version 1.0.0) was used for the automated analysis of T1 maps. Four radiologists, as study readers, performed manual analysis. The reference standard was the consensus result of the manual analysis by two additional expert readers. The segmentation performance of the DL algorithm and the correlation and agreement between the automated measurement and the reference standard were assessed. Interobserver agreement among the four radiologists was analyzed. Results: DL successfully segmented the myocardium in 99.3% of slices in the native T1 map and 89.8% of slices in the post-T1 map with Dice similarity coefficients of 0.86 ± 0.05 and 0.74 ± 0.17, respectively. Native T1 and ECV showed strong correlation and agreement between DL and the reference: for T1, r = 0.967 (95% confidence interval CI, 0.951-0.978) and bias of 9.5 msec (95% limits of agreement LOA, -23.6-42.6 msec); for ECV, r = 0.987 (95% CI, 0.980-0.991) and bias of 0.7% (95% LOA, -2.8%-4.2%) on per-subject basis. Agreements between DL and each of the four radiologists were excellent (intraclass correlation coefficient ICC of 0.98-0.99 for both native T1 and ECV), comparable to the pairwise agreement between the radiologists (ICC of 0.97-1.00 and 0.99-1.00 for native T1 and ECV, respectively). Conclusion: The DL algorithm allowed automated T1 and ECV measurements comparable to those of radiologists.