Marius Menza

A quantitative comparison of regional myocardial motion in mice, rabbits and humans using in-vivo phase contrast CMR

BackgroundGenetically manipulated animals like mice or rabbits play an important role in the exploration of human cardiovascular diseases. It is therefore important to identify animal models that closely mimic physiological and pathological human cardiac function.MethodsIn-vivo phase contrast cardiovascular magnetic resonance (CMR) was used to measure regional three-directional left ventricular myocardial motion with high temporal resolution in mice (N=18), rabbits (N=8), and humans (N=20). Radial, long-axis, and rotational myocardial velocities were acquired in left ventricular basal, mid-ventricular, and apical short-axis locations.ResultsRegional analysis revealed different patterns of motion: 1) In humans and rabbits, the apex showed slower radial velocities compared to the base. 2) Significant differences within species were seen in the pattern of long-axis motion. Long-axis velocities during systole were fairly homogeneously distributed in mice, whereas humans showed a dominant component in the lateral wall and rabbits in the base. 3) Rotational velocities and twist showed the most distinct patterns in both temporal evolution and relative contribution of base, mid-ventricle and apex, respectively. Interestingly, a marked difference in rotational behavior during early-systole was found in mice, which exhibited clockwise rotation in all slice locations compared to counter-clockwise rotation in rabbits and humans.ConclusionsPhase contrast CMR revealed subtle, but significantly different regional myocardial motion patterns in mice, rabbits and humans. This finding has to be considered when investigating myocardial motion pattern in small animal models of heart disease.

Dual-Contrast Molecular Imaging Allows Noninvasive Characterization of Myocardial Ischemia/Reperfusion Injury After Coronary Vessel Occlusion in Mice by Magnetic Resonance Imaging

Background— Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion. Methods and Results— Ischemia/reperfusion injury was induced in 10-week-old C57BL/6N mice by temporary ligation of the left anterior descending coronary artery. Activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody directed against a ligand-induced binding site (LIBS) on activated glycoprotein IIb/IIIa (LIBS-MPIOs). After injection and imaging of LIBS-MPIOs, late gadolinium enhancement was used to depict myocardial necrosis; these imaging experiments were also performed in P2Y12−/− mice. All imaging results were correlated to immunohistochemistry findings. Activated platelets were detectable by magnetic resonance imaging via a significant signal effect caused by LIBS-MPIOs in the area of left anterior descending coronary artery occlusion 2 hours after reperfusion. In parallel, late gadolinium enhancement identified the extent of myocardial necrosis. Immunohistochemistry confirmed that LIBS-MPIOs bound significantly to microthrombi in reperfused myocardium. Only background binding was found in P2Y12−/− mice. Conclusions— Dual molecular imaging of myocardial ischemia/reperfusion injury allows characterization of platelet-driven inflammation by LIBS-MPIOs and myocardial necrosis by late gadolinium enhancement. This noninvasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes and highlights the potential of molecular magnetic resonance imaging for characterizing ischemia/reperfusion injury.

Dual Contrast Molecular Imaging Allows Noninvasive Characterization of Myocardial Ischemia/Reperfusion Injury After Coronary Vessel Occlusion in Mice by MRI

Background— Inflammation and myocardial necrosis play important roles in ischemia/reperfusion injury after coronary artery occlusion and recanalization. The detection of inflammatory activity and the extent of myocardial necrosis itself are of great clinical and prognostic interest. We developed a dual, noninvasive imaging approach using molecular magnetic resonance imaging in an in vivo mouse model of myocardial ischemia and reperfusion. Methods and Results— Ischemia/reperfusion injury was induced in 10-week-old C57BL/6N mice by temporary ligation of the left anterior descending coronary artery. Activated platelets were targeted with a contrast agent consisting of microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody directed against a ligand-induced binding site (LIBS) on activated glycoprotein IIb/IIIa (LIBS-MPIOs). After injection and imaging of LIBS-MPIOs, late gadolinium enhancement was used to depict myocardial necrosis; these imaging experiments were also performed in P2Y12−/− mice. All imaging results were correlated to immunohistochemistry findings. Activated platelets were detectable by magnetic resonance imaging via a significant signal effect caused by LIBS-MPIOs in the area of left anterior descending coronary artery occlusion 2 hours after reperfusion. In parallel, late gadolinium enhancement identified the extent of myocardial necrosis. Immunohistochemistry confirmed that LIBS-MPIOs bound significantly to microthrombi in reperfused myocardium. Only background binding was found in P2Y12−/− mice. Conclusions— Dual molecular imaging of myocardial ischemia/reperfusion injury allows characterization of platelet-driven inflammation by LIBS-MPIOs and myocardial necrosis by late gadolinium enhancement. This noninvasive imaging strategy is of clinical interest for both diagnostic and prognostic purposes and highlights the potential of molecular magnetic resonance imaging for characterizing ischemia/reperfusion injury.

Cold ischaemic time and time after transplantation alter segmental myocardial velocities after heart transplantation

OBJECTIVES The aim of this study was to investigate changes in segmental, three-directional left ventricular (LV) velocities in patients after heart transplantation (Tx). METHODS Magnetic resonance tissue phase mapping was used to assess myocardial velocities in patients after Tx (n = 27) with normal LV ejection fraction (63 ± 5%) and those without signs of rejection. Regional wall motion and dyssynchrony were analysed in relation to cold ischaemic time (150 ± 57 min, median = 154 min), age of the donor heart (35 ± 13 years, median = 29 years), time after transplantation (32 ± 26 months, median = 31 months) and global LV morphology and function. RESULTS Segmental myocardial velocities were significantly altered in patients with cold ischaemic times >155 min resulting in an increase in peak systolic radial velocities (2 of 16 segments, P = 0.03-0.04) and reduced segmental diastolic long-axis velocities (5 of 16 segments, P = 0.01-0.04). Time after transplantation (n = 8 patients <12 months after Tx vs n = 19 >12 months) had a significant influence on systolic radial velocities (increased in 2 of 16 segments, P = 0.01-0.04) and diastolic long-axis velocities (reduced in 5 of 16 segments, P = 0.02-0.04). Correlation analysis and multiple regression revealed significant relationships of cold ischaemic time (R = -0.384, P = 0.048), the donor hearts age (β= 0.9, P = 0.01) and time from transplantation (β= -0.36, P = 0.03) with long-axis diastolic dyssynchrony. CONCLUSIONS Time after transplantation and cold ischaemic time strongly affect segmental systolic and diastolic motion in patients after Tx. The understanding of alterations in regional LV motion in the transplanted heart under stable conditions is essential in order to utilize this methodology in the future as a potentially non-invasive means of diagnosing transplant rejection.

In vitro study to simulate the intracardiac magnetohydrodynamic effect.

Blood flow causes induced voltages via the magnetohydrodynamic (MHD) effect distorting electrograms (EGMs) made during magnetic resonance imaging. To investigate the MHD effect in this context MHD voltages occurring inside the human heart were simulated in an in vitro model system inside a 1.5 T MR system.

Myocardial dysfunction in patients with aortic stenosis and hypertensive heart disease assessed by MR tissue phase mapping

To identify abnormalities of myocardial velocities in patients with left ventricular pressure overload using magnetic resonance tissue phase mapping (TPM).

Coronary magnetic resonance imaging after routine implantation of bioresorbable vascular scaffolds allows non-invasive evaluation of vascular patency

Background Evaluation of recurrent angina after percutaneous coronary interventions is challenging. Since bioresorbable vascular scaffolds (BVS) cause no artefacts in magnetic resonance imaging (MRI) due to their polylactate-based backbone, evaluation of vascular patency by MRI might allow for non-invasive assessment and triage of patients with suspected BVS failure. Methods Patients with polylactate-based ABSORB-BVS in proximal coronary segments were examined with 3 Tesla MRI directly (baseline) and one year after implantation. For assessment of coronary patency, a high-resolution 3D spoiled gradient echo pulse sequence with fat-saturation, T2-preparation (TE: 40 ms), respiratory and end-diastolic cardiac gating, and a spatial resolution of (1.08 mm)3 was positioned parallel to the course of the vessel for bright blood imaging. In addition, a 3D navigator-gated T2-weighted variable flip angle turbo spin echo (TSE) sequence with dual-inversion recovery black-blood preparation and elliptical k-space coverage was applied with a voxel size of (1.14 mm)3. For quantitative evaluation lumen diameters of the scaffolded areas were measured in reformatted bright and black blood MR angiography data. Results 11 patients with implantation of 16 BVS in the proximal coronary segments were included, of which none suffered from major adverse cardiac events during the one year follow up. Vascular patency in all segments implanted with BVS could be reliably assessed by MRI at baseline and after one year, whereas segments with metal stents could not be evaluated due to artefacts. Luminal diameter within the BVS remained constant during the one year period. One patient with atypical angina after BVS implantation was noninvasively evaluated showing a patent vessel, also confirmed by coronary angiography. Conclusions Coronary MRI allows contrast-agent free and non-invasive assessment of vascular patency after ABSORB-BVS implantation. This approach might be supportive in the triage and improvement of diagnostic workflows in patients with postinterventional angina and scaffold implantation. Trial registration German Register of Clinical Studies DRKS00007456

Preclinical 4D-flow magnetic resonance phase contrast imaging of the murine aortic arch

Purpose Cardiovascular diseases remain the number one death cause worldwide. Preclinical 4D flow phase contrast magnetic resonance imaging can provide substantial insights in the analysis of aortic pathophysiologies in various animal models. These insights may allow a better understanding of pathophysiologies, therapy monitoring, and can possibly be translated to humans. This study provides a framework to acquire the velocity field within the aortic arch. It analyses important flow values at different locations within the aortic arch. Imaging parameters with high temporal and spatial resolution are provided, that still allow combining this time-consuming method with other necessary imaging-protocols. Methods A new setup was established where a prospectively gated 4D phase contrast sequence is combined with a highly sensitive cryogenic coil on a preclinical magnetic resonance scanner. The sequence was redesigned to maintain a close to steady state condition of the longitudinal magnetization and hence to overcome steady state artifacts. Imaging parameters were optimized to provide high spatial and temporal resolution. Pathline visualizations were generated from the acquired velocity data in order to display complex flow patterns. Results Our setup allows data acquisition with at least two times the rate than that of previous publications based on Cartesian encoding, at an improved image quality. The “steady state” sequence reduces observed artifacts and provides uniform image intensity over the heart cycle. This made possible quantification of blood speed and wall shear stress (WSS) within the aorta and its branches. The highest velocities were observed in the ascending aorta with 137.5 ± 8 cm/s. Peak velocity values in the Brachiocephalic trunk were 57 ± 12 cm/s. Quantification showed that the peak flow occurs around 20 ms post R-wave in the ascending aorta. The highest mean axial wall shear stress was observed in the analysis plane between the left common carotid artery (LCCA) and the left subclavian artery. A stable image quality allows visualizing complex flow patterns by means of streamlines and for the first time, to the best of our knowledge, pathline visualizations from 4D flow MRI in mice. Conclusion The described setup allows analyzing pathophysiologies in mouse models of cardiovascular diseases in the aorta and its branches with better image quality and higher spatial and temporal resolution than previous Cartesian publications. Pathlines provide an advanced analysis of complex flow patterns in the murine aorta. An imaging protocol is provided that offers the possibility to acquire the aortic arch at sufficiently high resolution in less than one hour. This allows the combination of the flow assessment with other multifunctional imaging protocols.

4D tissue phase mapping: clinically viable acquisition protocol and new method of visualisation

Background Tissue phase mapping (TPM) has been shown to be capable of providing insights into healthy and diseased motion [1]. Typically 3 short-axis slices are acquired, providing full 3-directional velocity vectors but only in 2D slices, preventing the calculation of potentially important parameters such as through-plane strain rate. More recently, several studies have presented 4DTPM [2,3], however acquisition times can be unfeasibly long, image quality, temporal and spatial resolution is generally poor, and visualising the data is a challenge. This abstract presents initial application of EnSight (CEI, USA) visualisation to 4DTPM data, acquired with a duration, quality and resolution which do not prevent clinical translation. Methods A navigator-gated black-blood TPM sequence [4] was adapted to allow 3D acquisitions. A 3D slab with matrix size 120x160x8 (75% slice oversampling) was acquired with spatial resolution of 2x2x4mm and temporal resolution of 24.4ms (40 phases) in a healthy volunteer. PEAKGRAPPA [5] factor 5 led to acquisition time of 16m45s. Images were manually segmented using MATLAB (The Mathworks, MA) before importing into EnSight. Vector arrows were used at each pixel to represent speed at each position.

Effect of cold ischemic times and time after transplantation on regional myocardial motion after heart transplantation

Background Transplant rejection affects the course and survival after heart transplantation (HTx). As a non-invasive alternative to myocardial biopsy, which is the gold standard used for screening and for the diagnosis of rejection, regional left ventricular (LV) myocardial motion analysis has been suggested. But myocardial biopsy is invasive and its diagnostic value is restricted by high sample errors due to the patchy distribution of early rejection. Alterations of regional wall motion [1], especially in diastole, might be sensitive for the diagnosis. However, evaluation by echocardiography is limited in this context and LV motion after HTx differs from the motion of native hearts. We assessed the influence of cold ischemic time (CIT) and time after HTx on myocardial velocities in stable HTx patients.