Paul J. Cassidy

Fast, high‐resolution in vivo cine magnetic resonance imaging in normal and failing mouse hearts on a vertical 11.7 T system

To establish fast, high‐resolution in vivo cine magnetic resonance imaging (cine‐MRI) on a vertical 11.7‐T MR system and to investigate the stability of normal and failing mouse hearts in the vertical position.

Assessment of motion gating strategies for mouse magnetic resonance at high magnetic fields.

To assess the performance of motion gating strategies for mouse cardiac magnetic resonance (MR) at high magnetic fields by quantifying the levels of motion artifact observed in images and spectra in vivo.

Iron particles for noninvasive monitoring of bone marrow stromal cell engraftment into, and isolation of viable engrafted donor cells from, the heart.

Stem cells offer a promising approach to the treatment of myocardial infarction and prevention of heart failure. We have used iron labeling of bone marrow stromal cells (BMSCs) to noninvasively track cell location in the infarcted rat heart over 16 weeks using cine‐magnetic resonance imaging (cine‐MRI) and to isolate the BMSCs from the grafted hearts using the magnetic properties of the donor cells. BMSCs were isolated from rat bone marrow, characterized by flow cytometry, transduced with lentiviral vectors expressing green fluorescent protein (GFP), and labeled with iron particles. BMSCs were injected into the infarct periphery immediately following coronary artery ligation, and rat hearts were imaged at 1, 4, 10, and 16 weeks postinfarction. Signal voids caused by the iron particles in the BMSCs were detected in all rats at all time points. In mildly infarcted hearts, the volume of the signal void decreased over the 16 weeks, whereas the signal void volume did not decrease significantly in severely infarcted hearts. High‐resolution three‐dimensional magnetic resonance (MR) microscopy identified hypointense regions at the same position as in vivo. Donor cells containing iron particles and expressing GFP were identified in MR‐targeted heart sections after magnetic cell separation from digested hearts. In conclusion, MRI can be used to track cells labeled with iron particles in damaged tissue for at least 16 weeks after injection and to guide tissue sectioning by accurately identifying regions of cell engraftment. The magnetic properties of the iron‐labeled donor cells can be used for their isolation from host tissue to enable further characterization.

Molecular imaging perspectives

Molecular imaging is an emerging technology at the life science/physical science interface which is set to revolutionize our understanding and treatment of disease. The tools of molecular imaging are the imaging modalities and their corresponding contrast agents. These facilitate interaction with a biological target at a molecular level in a number of ways. The diverse nature of molecular imaging requires knowledge from both the life and physical sciences for its successful development and implementation. The aim of this review is to introduce the subject of molecular imaging from both life science and physical science perspectives. However, we will restrict our coverage to the prominent in vivo molecular imaging modalities of magnetic resonance imaging, optical imaging and nuclear imaging. The physical basis of these imaging modalities, the use of contrast agents and the imaging parameters of sensitivity, temporal resolution and spatial resolution are described. Then, the specificity of contrast agents for targeting and sensing molecular events, and some applications of molecular imaging in biology and medicine are given. Finally, the diverse nature of molecular imaging and its reliance on interdisciplinary collaboration is discussed.

In vivo cardiac 1H-MRS in the mouse

The mouse is the predominant animal model to study the effect of gene manipulations. Imaging techniques to define functional effects on the heart caused by genomic alterations are becoming increasingly routine in mice, yet methods for in vivo investigation of metabolic phenotypes in the mouse heart are lacking. In this work, cardiac 1H‐MRS was developed and applied in mouse hearts in vivo using a single‐voxel technique (PRESS). In normal C57Bl/6J mice, stability and reproducibility achieved by dedicated cardiac and respiratory gating was demonstrated by measuring amplitude and zero‐order phase changes of the unsuppressed water signal. Various cardiac metabolites, such as creatine, taurine, carnitine, or intramyocardial lipids were successfully detected and quantified relative to the total water content in voxels as small as 2 μl, positioned in the interventricular septum. The method was applied to a murine model of guanidinoacetate N‐methyltransferase (GAMT) deficiency, which is characterized by substantially decreased myocardial creatine levels. Creatine deficiency was confirmed noninvasively in myocardium of anesthetized GAMT‐/‐ mice. This is the first study to report the application of cardiac 1H‐MRS in mice in vivo. Magn Reson Med 52:1029–1035, 2004.

CINE-MR Imaging of the Normal and Infarcted Rat Heart Using an 11.7 T Vertical Bore MR System

MR imaging is uniquely placed to non-invasively study rodent cardiac structure and function. High-field MR scanners commonly have a vertical bore, and the purpose of this work was to demonstrate CINE-MR imaging in normal and infarcted rat hearts after determining hemodynamic stability when positioned vertically for imaging. Optimisation of imaging parameters was carried out prior to assessment of cardiac function in a group of normal and infarcted rat hearts. Rat hemodynamics were unaltered when vertical for 90 minutes, compared with horizontal measurements and rat cardiac parameters were measured accurately and reproducibly with our optimized CINE-MR protocol. A flip angle of 17.5 degrees was shown to provide optimal contrast for the assessment of structure and function, and, in contrast to our findings in mice, respiratory gating was not found to be essential. Hence, we conclude that vertical bore MR systems can be used to measure in vivo cardiac function in normal and infarcted rat hearts.

Serial high resolution 3D–MRI after aortic banding in mice: band internalization is a source of variability in the hypertrophic response

AbstractTransverse aortic constriction (TAC) is used as a model of left ventricular hypertrophy and failure; however, there is extensive variability in the hypertrophic response. In 43 mice that underwent TAC with a 7–0 polypropylene suture, 13 were identified by echocardiography with initial LV hypertrophy that halted or regressed over time. Post–mortem examination on 7 of these mice found the constricting band to be intact, but partially internalized into the aortic lumen, allowing blood flow around the stenosis. To confirm this prospectively in vivo we then followed 12 mice after TAC for 6 weeks, using a new high resolution 3D–MRI method to measure minimal aortic arch cross–sectional area (CSA). Three of the 12 mice developed a significantly increased aortic CSA (0.31 ± 0.15 on day 2 vs. 1.11 ± 0.29 mm2 on day 42; P < 0.05), which was independently confirmed by dissection. These mice had internalized part of the band within the aortic lumen and, by week 6, showed significantly less LV hypertrophy and better systolic function. Nine of the 12 mice showed no change in aortic CSA. Band internalization could be prevented when two banding sutures were placed side–by–side (n = 10). This is the first observation that a significant subset of animals following TAC bypass the stenosis resulting in partial regression of hypertrophy.

Long-term stability of cardiac function in normal and chronically failing mouse hearts in a vertical-bore MR system

We previously demonstrated stability of ventricular volumes and cardiac function in normal and in chronically failing mouse hearts in MR systems with a vertical-bore magnet for up to 1 h. However, in order to exploit the benefits of an increased magnetic field strength of these MR systems in more time-consuming studies required by, for example MR spectroscopy, we investigated whether cardiac function and ventricular volumes of healthy and infarcted mice would be affected in vertical position over a prolonged period. We applied high-resolution MR cine imaging on an 11.7 T vertical MR system to monitor cardiac functional parameters of normal and chronically failing mouse hearts over a period of 3 h in an upright position, with a temporal resolution of ≤15 min. We monitored left-ventricular volumes and cardiac functional parameters in both groups. In normal mice, we detected a decrease of left-ventricular end-systolic volumes by 8 μl and an approximately 23% increase of ejection fraction over time indicating a small but detectable degree of orthostatic dysregulation. Observed changes were more pronounced in mice with heart failure. Despite significant changes in left-ventricular volumes and function, absolute values measured for all functional cardiac parameters are consistent with near-physiological conditions. Thus, mice can be studied in high-field MR systems positioned vertically for 3 h.

Electromagnetic characterisation of MR RF coils using the transmission-line modelling method

The Transmission-Line Modelling (TLM) method is applied to the electromagnetic characterisation of RF coils and samples for magnetic resonance imaging ()MRI. Theoretical verification was performed using a simple surface coil. Experimental verification was performed using Alderman-Grant and birdcage coils constructed for use on a 7 T micro-imaging system. The modelling method enabled electromagnetic characteristics of frequency response, electromagnetic field generation, energy stored and power loss to be determined. From these parameters, coil resonant modes.B1 field profiles, voltages, currents, quality factor (Q),π/2 pulse length, and the equivalent lumped-element circuit components of resistance, inductance and capacitance were calculated. Equations are presented that enable a comprehensive electromagnetic characterisation of the RF coil and sample to be achieved based on the results of the TLM simulations. The use of the TLM method is extended to include the design of safe arbitrary multi-nuclear pulse sequences such that the specific absorption rate (SAR) of tissue, and RF coil component safety limits are not exceeded.