Sarah Jeuthe

T1 mapping in ischaemic heart disease

A unique feature of cardiac magnetic resonance is its ability to characterize myocardium. Proton relaxation times, T1, T2, and T2* are a reflection of the composition of individual tissues, and change in the presence of disease. Research into T1 mapping has largely been focused in the study of cardiomyopathies, but T1 mapping also shows huge potential in the study of ischaemic heart disease. In fact, the first cardiac T1 maps were used to characterize myocardial infarction. Robust high-resolution myocardial T1 mapping is now available for use as a clinical tool. This quantitative technique is simple to perform and analyse, minimally subjective, and highly reproducible. This review aims to summarize the present state of research on the topic, and to show the clinical potential of this method to aid the diagnosis and treatment of patients with ischaemic heart disease.

Mortality and morbidity in different immunization protocols for experimental autoimmune myocarditis in rats

We aimed to investigate the histological and clinical presentations of experimental autoimmune myocarditis (EAM) induced by different immunization schemes.

Alterations in creatine metabolism observed in experimental autoimmune myocarditis using ex vivo proton magic angle spinning MRS.

Experimental autoimmune myocarditis (EAM) in rodents is an accepted model of myocarditis and dilated cardiomyopathy (DCM). Altered metabolism is thought to play an important role in the pathogenesis of DCM and heart failure (HF). Study of the metabolism may provide new diagnostic information and insights into the mechanisms of myocarditis and HF. Proton MRS (1H‐MRS) has not yet been used to study the changes occurring in myocarditis and subsequent HF. We aimed to explore the changes in creatine metabolism using this model and compare them with the findings in healthy animals.

Comparison of pre- and post-contrast myocardial T1 with histology findings in Experimental autoimmune myocarditis in rats.

Background Magnetic resonance imaging as a noninvasive method offers diagnostic and prognostic information in myocarditis. T1 mapping techniques aim to overcome the limitations of late gadolinium enhancement to assess diffuse fibrosis and inflammatory infiltrates. Using an established animal model of myocarditis, the aim of this study was to measure myocardial T1 before the onset, and in the acute and chronic stages of the disease and to compare its course with histological and immunohistochemistry findings.

T1 mapping allows the study of the development of oedema in a small animal model of Ischemia-Reperfusion

Background Ischemic cell death is characterised by cellular oedema. Reperfusion may be expected to increase myocardial oedema via hyperaemia and osmotic changes. Cardiovascular magnetic resonance (CMR) can be used to detect oedema using T2 weighted imaging, but this technique does not allow the study of possible changes in oedema with reperfusion. The purpose of this study was to examine the development of oedema in a small animal model of Ischemia-Reperfusion using serial T1 mapping.

Cellular mechanisms of metabolic syndrome-related atrial decompensation in a rat model of HFpEF

Heart failure (HF) with preserved ejection fraction (HFpEF) is present in about 50% of HF patients. Atrial remodeling is common in HFpEF and associated with increased mortality. We postulate that atrial remodeling is associated with atrial dysfunction in vivo related to alterations in cardiomyocyte Calcium (Ca) signaling and remodeling. We examined atrial function in vivo and Ca transients (CaT) (Fluo4-AM, field stim) in atrial cardiomyocytes of ZSF-1 rats without (Ln; lean hypertensive) and with metabolic syndrome (Ob; obese, hypertensive, diabetic) and HFpEF. RESULTS At 21weeks Ln showed an increased left ventricular (LV) mass and left ventricular end-diastolic pressure (LVEDP), but unchanged left atrial (LA) size and preserved atrial ejection fraction vs. wild-type (WT). CaT amplitude in atrial cardiomyocytes was increased in Ln (2.9±0.2 vs. 2.3±0.2F/F0 in WT; n=22 cells/group; p<0.05). Studying subcellular Ca release in more detail, we found that local central cytosolic CaT amplitude was increased, while subsarcolemmal CaT amplitudes remained unchanged. Moreover, Sarcoplasmic reticulum (SR) Ca content (caffeine) was preserved while Ca spark frequency and tetracaine-dependent SR Ca leak were significantly increased in Ln. Ob mice developed a HFpEF phenotype in vivo, LA area was significantly increased and atrial in vivo function was impaired, despite increased atrial CaT amplitudes in vitro (2.8±0.2; p<0.05 vs. WT). Ob cells showed alterations of the tubular network possibly contributing to the observed phenotype. CaT kinetics as well as SR Ca in Ob were not significantly different from WT, but SR Ca leak remained increased. Angiotensin II (Ang II) reduced in vitro cytosolic CaT amplitudes and let to active nuclear Ca release in Ob but not in Ln or WT. SUMMARY In hypertensive ZSF-1 rats, a possibly compensatory increase of cytosolic CaT amplitude and increased SR Ca leak precede atrial remodeling and HFpEF. Atrial remodeling in ZSF-1 HFpEF is associated with an altered tubular network in-vitro and atrial contractile dysfunction in vivo, indicating insufficient compensation. Atrial cardiomyocyte dysfunction in vitro is induced by the addition of angiotensin II.

Assessment of cardiac function and myocardial morphology using small animal Look-Locker inversion recovery (SALLI) MRI in rats.

Small animal magnetic resonance imaging is an important tool to study cardiac function and changes in myocardial tissue. The high heart rates of small animals (200 to 600 beats/min) have previously limited the role of CMR imaging. Small animal Look-Locker inversion recovery (SALLI) is a T1 mapping sequence for small animals to overcome this problem. T1 maps provide quantitative information about tissue alterations and contrast agent kinetics. It is also possible to detect diffuse myocardial processes such as interstitial fibrosis or edema. Furthermore, from a single set of image data, it is possible to examine heart function and myocardial scarring by generating cine and inversion recovery-prepared late gadolinium enhancement-type MR images. The presented video shows step-by-step the procedures to perform small animal CMR imaging. Here it is presented with a healthy Sprague-Dawley rat, however naturally it can be extended to different cardiac small animal models.

T1 measurements in a rat model of acute myocardial ischemia/reperfusion

Background Myocardial ischemia causes local edema, leading to prolongation of both T1 and T2. In clinical MRI, T2weighted techniques are commonly used to visualize myocardial edema. The aim was to study the acute T1 changes in-vivo in a novel closed chest animal model of myocardial ischemia/reperfusion using T1 mapping by SALLI in order to test if this parametric approach could provide additional diagnostic information as compared to conventional MRI.

Clinical and histological presentations of experimental autoimmune myocarditis in rats using different immunization schemes

Background Myocarditis is an inflammatory cardiac disease with a wide range of symptoms and various etiologies. The diagnostic workup and the treatment of myocarditis remain highly controversial. Therefore, there is a high demand for reliable animal models. Experimental autoimmune myocarditis (EAM) represents a model of human myocarditis and heart failure. In this study we investigated the histological, functional and clinical presentations of EAM induced by different immunization schemes. Methods Male young Lewis rats were divided into 5 groups immunized by porcine myocardial myosin: 1 mg subcutaneously (SC) on day 0 and 7; 0.25 mg subcutaneously into rear footpads (RF) on day 0; 0.5 mg RF on day 0; and 1 mg RF on day 0; and a sham group, injected with a vehicle solution without myosin into the RF on day 0. Rats were sacrificed on day 21 after assessment of left ventricular (LV) function by cardiac magnetic resonance imaging and cardiac catheterization under isoflurane anesthesia. The ventricle weight was measured and the location, type and degree of myocardial inflammatory infiltrates were determined by conventional histology and immunohistochemistry (CD 68). Results Rats immunized in the RF showed a mortality of 20%, 20% and 44% for the 0.25 mg, 0.5 mg and 1 mg myosin doses respectively, while the SC group and the RF sham group yielded a mortality of 0%. Morbidity as defined by inflammatory infiltrates on HE staining was 22% in the SC immunized rats, 0% in the RF sham group and 100% in all actively RF immunized groups. Histologically we observed macrophage-rich inflammatory infiltrates in both ventricles. All RF groups immunized with myosin showed augmented relative ventricle weight and spleen weight, increased LV end-diastolic pressure, reduced LV developed pressure and reduced LV ejection fraction, without any dose-dependend effect. Conclusions

Assessment of acute myocardial ischemia with unenhanced T1 mapping MR imaging

Methods 8 rats had an inflatable balloon coronary occluder surgically inserted via thoracotomy. They were allowed to recover for 10-14 days. MRI was performed to obtain baseline measurement of ventricular function. T1 mapping was performed using the Small-Animal LookLocker Inversion Recovery (SALLI) technique. Without removing the animals from the scanner, the left coronary artery was occluded for 30 minutes. Myocardial function and T1 were measured during ischemia. MRI was performed on a whole-body 3.0-T MR unit with a 70 mm solenoid coil for rats. After generation of survey images and of a long-axis set of cine images, a stack of LV short-axis cine images was acquired to assess global function. Short axis SALLI MR imaging was performed using the same short axis orientation in the mid ventricle, distal to the occluder. Typical SALLI parameters were as follows: 64 x 64 mm field of view, 0.60 x 0.60 mm pixel size, 3.0 mm-thick sections, 5.2/2.2, 10° flip angle, 4000 ms AD, 4000 ms RD, 12 phases (i.e., temporal resolution of 16.7 ms at 300 beats per minute), temporal undersampling factor of two, three signals acquired, and acquisition time of 8 minutes 30 seconds per slice. SALLI imaging was repeated throughout the duration of ischemia. Images were transferred to a dedicated software package and T1 values were obtained for the left ventricle at baseline, and then for both the ischemic region of interest identified by myocardial hypokinesis and a remote zone unaffected by the coronary occlusion.