Early Detection and Serial Monitoring of Anthracycline-Induced Cardiotoxicity Using T1-mapping Cardiac Magnetic Resonance Imaging: An Animal Study.

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.

Myocardial Characterization Using Dual-Energy CT in Doxorubicin-Induced DCM: Comparison With CMR T1-Mapping and Histology in a Rabbit Model.

OBJECTIVES: This study sought to evaluate whether patterns of myocardial change in doxorubicin-induced dilated cardiomyopathy determined using dual-energy computed tomography (CT) were similar to characterization by extracellular volume fraction (ECV) using cardiac magnetic resonance (CMR) T1-mapping and collagen volume fraction (CVF) measured using histology. BACKGROUND: Anthracycline chemoagents are effective against a wide range of malignant conditions. However, cardiotoxicity is a well-known adverse effect of these drugs. Dual-energy CT could be as useful as magnetic resonance (MR) to evaluate myocardial change in anthracycline-induced cardiotoxicity. METHODS: A dilated cardiomyopathy rabbit model was generated by injecting 11 adult New Zealand rabbits with 1.0 mg/kg of doxorubicin twice weekly for 16 weeks. Contrast-enhanced dual-energy CT and pre-contrast and post-contrast T1-mapping CMR using a prototype modified Look-Locker inversion recovery on a clinical 3-T scanner were performed on 15 rabbits, including 4 control animals, to calculate ECV at baseline, and at 6, 12, and 16 weeks after doxorubicin administration. RESULTS: The mean ECV values (%) on CT and CMR at 6, 12, and 16 weeks after modeling were significantly higher than those measured at baseline (CT ECV: 35.3%, 41.9%, 42.1% vs. 28.5%; MR ECV: 32.6%, 35.8%, 41.3% vs. 28.8%, respectively; all p < 0.001). CT ECV and MR ECV values were well correlated (r = 0.888; p < 0.001). Both were well correlated with CVF on histology (CT ECV vs. CVF, r = 0.925, p < 0.001 and MR ECV vs. CVF, r = 0.961, p < 0.001, respectively). CONCLUSIONS: Dual-energy CT ECV correlated well with CMR and histology. Dual-energy CT is useful for characterizing doxorubicin-induced cardiomyopathy by measuring ECV fraction; however, further technical improvements are desirable to lower motion artifact and improve image quality of the iodine map.

Dose-dependent influence of short-term intermittent ethanol intoxication on cerebral neurochemical changes in rats detected by ex vivo proton nuclear magnetic resonance spectroscopy.

The aim of this study was to quantitatively assess the effects of short-term intermittent ethanol intoxication on cerebral metabolite changes among sham controls (CNTL), low-dose ethanol (LDE)-exposed, and high-dose ethanol (HDE)-exposed rats, which were determined with ex vivo high-resolution spectra. Eight-week-old male Wistar rats were divided into three groups. Twenty rats in the LDE (n=10) and the HDE (n=10) groups received ethanol doses of 1.5 and 2.5 g/kg, respectively, through oral gavage every 8h for 4days. At the end of the 4-day intermittent ethanol exposure, one-dimensional ex vivo 500-MHz ¹H nuclear magnetic resonance spectra were acquired from 30 samples of the frontal cortex region (from the three groups). Normalized total N-acetylaspartate (tNAA: NAA+NAAG [N-acetylaspartyl-glutamate]), GABA, and glutathione (GSH) levels were significantly lower in the frontal cortex of the HDE-exposed rats than that of the LDE-exposed rats. Moreover, compared to the CNTL group, the LDE rats exhibited significantly higher normalized GABA levels. The six pairs of normalized metabolite levels were positively (+) or negatively (-) correlated in the rat frontal cortex as follows: tNAA and GABA (+), tNAA and aspartate (Asp) (+), myo-Inositol (mIns) and Asp (-), mIns and alanine (+), mIns and taurine (+), and mIns and tNAA (-). Our results suggested that short-term intermittent ethanol intoxication might result in neuronal degeneration and dysfunction, changes in the rate of GABA synthesis, and oxidative stress in the rat frontal cortex. Our ex vivo(1)H high-resolution magic angle spinning nuclear magnetic resonance spectroscopy results suggested some novel metabolic markers for the dose-dependent influence of short-term intermittent ethanol intoxication in the frontal cortex.