Yin Wu

MR diffusion tensor imaging study of postinfarct myocardium structural remodeling in a porcine model

This study aimed to investigate postinfarct left ventricular (LV) fiber structural alterations by ex vivo diffusion tensor imaging (DTI) in a porcine heart model. In vivo cardiac MR imaging was first performed to measure ventricular function in six adult pigs with septal infarction near apex induced by the LAD ligation 13 weeks earlier. Hearts were then excised from the infarct pigs (n = 6) and six intact controls (n = 6) and fixed in formalin. High‐resolution DTI was employed to examine changes in fractional anisotropy (FA), apparent diffusion coefficient (ADC), and transmural helix angle distribution in the infarct, adjacent and remote regions as compared to the sham regions in the controls. FA values were found to decrease in the infarct and differ between the adjacent and remote regions. ADC increase in the infarct region was substantial, while changes in the adjacent and remote regions were insignificant. Structurally, the double‐helix myocardial structure shifted toward more left‐handed around the infarcted myocardium. Accordingly, the histological analysis revealed clear fiber structural degradation in the adjacent region. These findings confirmed the subtle alterations in the myocardial fiber quality and structure not only in the infarcted but also in the surrounding noninfarcted myocardium or borderzone. Magn Reson Med 58:687–695, 2007.

C-Reactive Protein Promotes Cardiac Fibrosis and Inflammation in Angiotensin II–Induced Hypertensive Cardiac Disease

C-reactive protein (CRP) is a risk factor or biomarker for cardiovascular diseases, including hypertension. The present study investigated the functional importance of human CRP in hypertensive cardiac remodeling by a chronic infusion of angiotensin II (Ang II) into mice that express human CRP. Compared with the wild-type mice, although Ang II infusion caused an equally high systolic blood pressure, levels of human CRP were further elevated, and cardiac remodeling was markedly exacerbated in mice that express human CRP, resulting in a significant reduction in the left ventricular ejection fraction and fractional shortening and an increase in cardiac fibrosis (collagen I and III and &agr;-smooth muscle actin) and inflammation (interleukin 1&bgr; and tumor necrosis factor-&agr;). The enhancement in cardiac remodeling in mice that express human CRP was associated with further upregulation of the Ang II type I receptor and transforming growth factor-&bgr;1 and overactivation of both transforming growth factor-&bgr;/Smad and nuclear factor-&kgr;B signaling pathways. Furthermore, in vitro studies in cardiac fibroblasts revealed that CRP alone was able to significantly induce expression of the Ang II type I receptor, collagen I/III, and &agr;-smooth muscle actin, as well as proinflammation cytokines (interleukin 1&bgr; and tumor necrosis factor-&agr;), which was further enhanced by addition of Ang II. In conclusion, CRP is not only a biomarker but also a mediator in Ang II-mediated cardiac remodeling. Enhanced upregulation of the Ang II type I receptor and activation of the transforming growth factor-&bgr;/Smad and nuclear factor-&kgr;B signaling pathways may be the mechanisms by which CRP promotes cardiac fibrosis and inflammation under high Ang II conditions.

Proarrhythmic risk of embryonic stem cell–derived cardiomyocyte transplantation in infarcted myocardium

BACKGROUND Cellular replacement strategies using embryonic stem cells (ESCs) and their cardiac derivatives are emerging as novel experimental therapeutic paradigms for the treatment of post-myocardial infarction (MI) left ventricular (LV) dysfunction; however, their potential proarrhythmic risk remains unclear. OBJECTIVE The purpose of this study was to investigate the functional effect and proarrhythmic risk of ESC transplantation in a mouse model of MI. METHODS We compared the functional effects and proarrhythmic risk of direct intramyocardial transplantation of 3 × 10(5) undifferentiated mouse ESCs (MI+ESC group, n = 33) and mouse ESC-derived cardiomyocytes (MI+ESC-CM group, n = 40) versus culture medium (MI group, n = 33) at the infarct border zone in a mouse model of acute MI. LV performance was assessed with serial cardiac magnetic resonance imaging (MRI) at 1 and 3 week(s) post-MI, and invasive LV pressure measurement was assessed (dP/dt) at 4 weeks before sacrifice for histological examination. Furthermore, electrophysiological study was also performed in another set of animals in each group (n = 24) to assess for proarrhythmias after transplantation. RESULTS In vitro cellular electrophysiological study demonstrated that ESC-CMs exhibit arrhythmogenesis including automaticity, lengthened action potential duration, and depolarized resting membrane potential. At 4 weeks, the MI+ESC-CM group (21/40, 53%) had a higher mortality rate compared with those in the MI group (10/33, 30%, P = .08) and in the MI+ESC group (7/33, 21%, P = .012). Electrophysiological study showed a significantly higher incidence of inducible ventricular tachyarrhythmias in the MI+ESC-CM group (13/24, 54%) compared with in the MI group (6/24, 21%, P = .039) and in the MI+ESC group (5/24, 21%, P = .017). Cardiac MRI showed similar improvement in LV ejection fraction in the MI+ESC and MI+ESC-CM groups compared with in the MI group at 1 week (27.5% ± 3.8%; 30.3% ± 5.2% vs. 12.4% ± 1.4%; P < .05) and 3 weeks (29.8% ± 3.9%; 27.0% ± 4.8% vs. 10.6% ± 2.8%; P < .05) post-MI, respectively. Furthermore, invasive hemodynamic assessment at 4 weeks showed significant similar improvement in LV +dP/dt in the MI+ESC (2,644 ± 391 mmHg/s, P < .05) and MI+ESC-CM groups (2,539 ± 389 mmHg/s; P < .05) compared with in the MI group (2,042 ± 406 mmHg/s). CONCLUSIONS Our results demonstrate that transplantation of undifferentiated ESCs and ESC-CMs provides similar improvement in cardiac function post-MI. However, transplantation of ESC-CMs is associated with a significantly higher prevalence of inducible ventricular tachyarrhythmias and early mortality than transplantations with ESCs.

MR study of the effect of infarct size and location on left ventricular functional and microstructural alterations in porcine models

To investigate the effect of infarct size and location on left ventricular (LV) functional and microstructural alterations in well‐established porcine models.

MR Study of Postnatal Development of Myocardial Structure and Left Ventricular Function

To investigate postnatal development of left ventricular (LV) cardiac function and myocardium structure.

Transmural heterogeneity of left ventricular myocardium remodeling in postinfarct porcine model revealed by MR diffusion tensor imaging

To investigate the transmural heterogeneity of left ventricular myocardium structural remodeling.

A review of optimization and quantification techniques for chemical exchange saturation transfer MRI toward sensitive in vivo imaging.

Chemical exchange saturation transfer (CEST) MRI is a versatile imaging method that probes the chemical exchange between bulk water and exchangeable protons. CEST imaging indirectly detects dilute labile protons via bulk water signal changes following selective saturation of exchangeable protons, which offers substantial sensitivity enhancement and has sparked numerous biomedical applications. Over the past decade, CEST imaging techniques have rapidly evolved owing to contributions from multiple domains, including the development of CEST mathematical models, innovative contrast agent designs, sensitive data acquisition schemes, efficient field inhomogeneity correction algorithms, and quantitative CEST (qCEST) analysis. The CEST system that underlies the apparent CEST-weighted effect, however, is complex. The experimentally measurable CEST effect depends not only on parameters such as CEST agent concentration, pH and temperature, but also on relaxation rate, magnetic field strength and more importantly, experimental parameters including repetition time, RF irradiation amplitude and scheme, and image readout. Thorough understanding of the underlying CEST system using qCEST analysis may augment the diagnostic capability of conventional imaging. In this review, we provide a concise explanation of CEST acquisition methods and processing algorithms, including their advantages and limitations, for optimization and quantification of CEST MRI experiments.

Attenuation of Left Ventricular Adverse Remodeling With Epicardial Patching After Myocardial Infarction

BACKGROUND Previous studies suggested that epicardial patch applied to the infarcted site after acute myocardial infarction (MI) can alleviate left ventricular (LV) remodeling and improve cardiac performance; however, the effects of regional epicardial patch on chronic phase of LV remodeling remain unclear. METHODS AND RESULTS We studied 20 pigs with MI induced by distal embolization and impaired LV ejection fraction (LVEF < 45%) as detected by gadolinium-enhanced cardiac magnetic resonance imaging (MRI). Eight weeks post-MI, all animal underwent open chest procedure for sham surgery (control, n = 12) or patch implantation over the infarcted lateral LV wall (patch group, n = 12). In the patch group, +dP/dt increased and LV end-diastolic pressure decreased at 20 weeks compared with immediately post-MI and at 8 weeks (P < .05), but not in the control group (P > .05). As determined by cardiac MRI, LV end-diastolic and end-systolic volumes increased at 20 weeks compared with 8 weeks in both groups (P < .05). However, the increase in LV end-diastolic volume (+14.1 +/- 1.8% vs. +6.6 +/- 2.1%, P = .015) and LV end-systolic volume (+12.1 +/- 2.4% vs. -4.7 +/- 3.7%, P = .0015) were significantly greater in the control group compared with the patch group. Furthermore, the percentage increase in LVEF (+17.3 +/- 4.9% vs. +4.1 +/- 3.9%, P = .048) from 8 to 20 weeks was significantly greater in the patch group compared with the control group. Histological examination showed that LV wall thickness at the infarct region and adjacent peri-infarct regions were significantly greater in the patch group compared with the control group (P < .05). CONCLUSION Regional application of a simple, passive synthetic epicardial patch increased LV wall thickness at the infarct region, attenuated LV dilation, and improved LVEF and +dP/dt in a large animal model of MI.

Diffusion Tensor MRI Study of Myocardium Structural Remodeling after Infarction in Porcine Model

Investigation of infarct myocardium structure will lead to better understanding of functional adaptation and remodeling. Diffusion tensor magnetic resonance imaging (DTI) provides a means for rapid and nondestructive characterization of the three-dimensional fiber architecture of myocardium. DTI studies were performed on 10 excised, formalin-fixed hearts of both infarct (two months after left anterior descending coronary artery (LAD) occlusion surgery, n=4) and control (n=6) porcine. Each slice was divided into eight segments, and fractional anisotropy (FA) value and helix angle were measured in multiples short-axis slices, respectively. Infarct myocardium exhibited decreased FA value, flatter helix angle courses fluctuating around small helix angle with greater standard error of the mean (SEM) and smaller range of helix angle. The results provide structure information of infarct myocardium

Comparison of image sensitivity between conventional tensor‐based and fast diffusion kurtosis imaging protocols in a rodent model of acute ischemic stroke

Diffusion kurtosis imaging (DKI) can offer a useful complementary tool to routine diffusion MRI for improved stratification of heterogeneous tissue damage in acute ischemic stroke. However, its relatively long imaging time has hampered its clinical application in the emergency setting. A recently proposed fast DKI approach substantially shortens the imaging time, which may help to overcome the scan time limitation. However, to date, the sensitivity of the fast DKI protocol for the imaging of acute stroke has not been fully described. In this study, we performed routine and fast DKI scans in a rodent model of acute stroke, and compared the sensitivity of diffusivity and kurtosis indices (i.e. axial, radial and mean) in depicting acute ischemic lesions. In addition, we analyzed the contrast‐to‐noise ratio (CNR) between the ipsilateral ischemic and contralateral normal regions using both conventional and fast DKI methods. We found that the mean kurtosis shows a relative change of 47.1 ± 7.3% between the ischemic and contralateral normal regions, being the most sensitive parameter in revealing acute ischemic injury. The two DKI methods yielded highly correlated diffusivity and kurtosis measures and lesion volumes (R2 ⩾ 0.90, p < 0.01). Importantly, the fast DKI method exhibited significantly higher CNR of mean kurtosis (1.6 ± 0.2) compared with the routine tensor protocol (1.3 ± 0.2, p < 0.05), with its CNR per unit time (CNR efficiency) approximately doubled when the scan time was taken into account. In conclusion, the fast DKI method provides excellent sensitivity and efficiency to image acute ischemic tissue damage, which is essential for image‐guided and individualized stroke treatment. Copyright