Steffen Bohl

Delayed enhancement cardiac magnetic resonance imaging reveals typical patterns of myocardial injury in patients with various forms of non-ischemic heart disease

Background Late gadolinium-hyperenhancement (LHE) on cardiac Magnetic Resonance Imaging (CMR) has been linked to cardiovascular risk in ischemic and non-ischemic heart disease. We aimed to systematically categorize LHE-patterns in a variety of non-ischemic heart diseases (NIHD) and to explore their relationship with left ventricular (LV) function. Methods In a retrospective database search, 156 patients with NIHD who exhibited LHE on CMR were identified. All images were re-analyzed stepwise. LHE was correlated to LV functional parameters. Cardiac magnetic resonance (CMR) was conducted on 1.5xa0T scanners. Results Typically, LHE spared the subendocardium. Consistent LHE-patterns were observed in myocarditis, hypertrophic and dilated cardiomyopathy and systemic vasculitis. No conclusive LHE-patterns were observed in patients with aortic stenosis, arterial hypertension, lupus erythematosus, sarcoidosis, ventricular arrhythmia and in a mixed subgroup of rare NIHDs. There was no significant relationship between LHE and ejection fraction. There was no correlation between enddiastolic volume and LHE in either myocarditis (Pxa0=xa00.13) or dilated cardiomyopathy (Pxa0=xa00.62). LHE was unrelated to LV-mass in aortic stenosis (Pxa0=xa00.13) and hypertrophic cardiomyopathy (Pxa0=xa00.38). Conclusions Distinct LHE patterns exist in various NIHDs and their visualization may ultimately aid diagnosis. Unlike in ischemic heart disease, the structure-function relationship does not appear to be strong.

Advanced methods for quantification of infarct size in mice using three-dimensional high-field late gadolinium enhancement MRI

Conventional methods to quantify infarct size after myocardial infarction in mice are not ideal, requiring either tissue destruction for histology or relying on nondirect measurements such as wall motion. We therefore implemented a fast, high-resolution method to directly measure infarct size in vivo using three-dimensional (3D) late gadolinium enhancement MRI (3D-LGE). Myocardial T1 relaxation was quantified at 9.4 Tesla in five mice, and reproducibility was tested by repeat imaging after 5 days. In a separate set of healthy and infarcted mice (n = 8 of each), continuous T1 measurements were made following intravenous or intraperitoneal injection of a contrast agent (0.5 micromol/g gadolinium-diethylenetriamine pentaacetic acid). The time course of T1 contrast development between viable and nonviable myocardium was thereby determined, with optimal postinjection imaging windows and inversion times identified. Infarct sizes were quantified using 3D-LGE and compared with triphenyltetrazolium chloride histology on day 1 after infarction (n = 8). Baseline myocardial T1 was highly reproducible: the mean value was 952 +/- 41 ms. T1 contrast peaked earlier after intravenous injection than with intraperitoneal injection; however, contrast between viable and nonviable myocardium was comparable for both routes (P = 0.31), with adequate contrast remaining for at least 60 min postinjection. Excellent correlation was obtained between infarct sizes derived from 3D-LGE and histology (r = 0.91, P = 0.002), and Bland-Altman analysis indicated good agreement free from systematic bias. We have validated an improved 3D MRI method to noninvasively quantify infarct size in mice with unsurpassed spatial resolution and tissue contrast. This method is particularly suited to studies requiring early quantification of initial infarct size, for example, to measure damage before intervention with stem cells.

Refined approach for quantification of in vivo ischemia-reperfusion injury in the mouse heart

Cardiac ischemia-reperfusion experiments in the mouse are important in vivo models of human disease. Infarct size is a particularly important scientific readout as virtually all cardiocirculatory pathways are affected by it. Therefore, such measurements must be exact and valid. The histological analysis, however, remains technically challenging, and the resulting quality is often unsatisfactory. For this report we have scrutinized each step involved in standard double-staining histology. We have tested published approaches and challenged their practicality. As a result, we propose an improved and streamlined protocol, which consistently yields high-quality histology, thereby minimizing experimental noise and group sizes.

T2-mapping of ischaemia/reperfusion-injury in the in vivo mouse heart

Introduction Oedema is a key feature of acute ischaemia/reperfusion (IR) injury. As such, it is a diagnostic and potentially therapeutic target, assessable using MRI. To date, its application in the mouse heart is limited due to the challenges associated with low SNR inherent in T2-weighting, miniscule anatomy, and rapid motion. Absolute quantification of transverse relaxation time (T2-mapping) circumvents SNR constraints and may be an alternative to T2weighted imaging. We have therefore measured myocardial T2 in IR-mice and related T2-maps to the histological area-at-risk (AAR)

Single Lipoprotein Apheresis Session Improves Cardiac Microvascular Function in Patients With Elevated Lipoprotein(a): Detection by Stress/Rest Perfusion Magnetic Resonance Imaging: Cardiac Perfusion after Lp(a) Apheresis

The aim of this study was to explore the effects of a single lipoprotein apheresis session on myocardial stress/rest (S/R) perfusion in patients with elevated lipoprotein(a) (Lp(a)) and coronary artery disease using cardiac magnetic resonance imaging. Twenty patients with Lp(a)u2003>u200360u2003mg/dL and coronary artery disease were randomized into a control or a treatment group. Both groups underwent cardiac magnetic resonance imaging with assessment of left ventricular function, perfusion and viability, and the treatment group underwent lipoprotein apheresis immediately afterwards. Repeat magnetic resonance imaging was performed at 24u2003h for both groups and at 96u2003h for just the treatment group. The transmyocardial perfusion gradient (i.e. endo‐epi ratio [EER]) was determined and a comprehensive parameter of resting and adenosine‐induced stress perfusion was derived (EER‐S/R). While the hematocrit remained unchanged, apheresis reduced lipoproteins and rheological parameters: Lp(a)u2003−u200355.1%, total cholesterolu2003−u200334.5%, low density lipoprotein (LDL)u2003−u200354.6%, Lp(a)‐corrected LDLu2003−u200354.3%, high density lipoproteinu2003−u200317.4%, apolipoprotein Bu2003−u200339.2%, plasma viscosityu2003−u200310.7%, and fibrinogenu2003−u200330.6% at 24u2003h (Pu2003<u20030.05 for all). At 96u2003h these parameters, except for plasma viscosity, apolipoprotein B and Lp(a)‐corrected LDL, recovered but did not reach baseline values (Pu2003<u20030.05 for all). The EER‐S/R at 24u2003h was lowered by therapy (ΔEER‐S/R 5%; Pu2003<u20030.03), whereas this effect disappeared at 96u2003h. The ejection fraction (EF) was slightly improved at 24u2003h (67.07u2003±u20036.28% vs. 64.89u2003±u20036.39%; ΔEF 2.2%, Pu2003<u20030.05) and returned to baseline at 96u2003h. In the control group no corresponding changes were detected. In conclusion, cardiac magnetic resonance imaging detects subtle treatment‐related changes in regional myocardial perfusion in patients with elevated Lp(a) and coronary artery disease undergoing lipoprotein apheresis.

Single lipoprotein apheresis session improves cardiac microvascular function in patients with elevated lipoprotein(a)

The aim of this study was to explore the effects of a single lipoprotein apheresis session on myocardial stress/rest (S/R) perfusion in patients with elevated lipoprotein(a) (Lp(a)) and coronary artery disease using cardiac magnetic resonance imaging. Twenty patients with Lp(a)u2003>u200360u2003mg/dL and coronary artery disease were randomized into a control or a treatment group. Both groups underwent cardiac magnetic resonance imaging with assessment of left ventricular function, perfusion and viability, and the treatment group underwent lipoprotein apheresis immediately afterwards. Repeat magnetic resonance imaging was performed at 24u2003h for both groups and at 96u2003h for just the treatment group. The transmyocardial perfusion gradient (i.e. endo‐epi ratio [EER]) was determined and a comprehensive parameter of resting and adenosine‐induced stress perfusion was derived (EER‐S/R). While the hematocrit remained unchanged, apheresis reduced lipoproteins and rheological parameters: Lp(a)u2003−u200355.1%, total cholesterolu2003−u200334.5%, low density lipoprotein (LDL)u2003−u200354.6%, Lp(a)‐corrected LDLu2003−u200354.3%, high density lipoproteinu2003−u200317.4%, apolipoprotein Bu2003−u200339.2%, plasma viscosityu2003−u200310.7%, and fibrinogenu2003−u200330.6% at 24u2003h (Pu2003<u20030.05 for all). At 96u2003h these parameters, except for plasma viscosity, apolipoprotein B and Lp(a)‐corrected LDL, recovered but did not reach baseline values (Pu2003<u20030.05 for all). The EER‐S/R at 24u2003h was lowered by therapy (ΔEER‐S/R 5%; Pu2003<u20030.03), whereas this effect disappeared at 96u2003h. The ejection fraction (EF) was slightly improved at 24u2003h (67.07u2003±u20036.28% vs. 64.89u2003±u20036.39%; ΔEF 2.2%, Pu2003<u20030.05) and returned to baseline at 96u2003h. In the control group no corresponding changes were detected. In conclusion, cardiac magnetic resonance imaging detects subtle treatment‐related changes in regional myocardial perfusion in patients with elevated Lp(a) and coronary artery disease undergoing lipoprotein apheresis.