Experimental myocardial infarction (MI) in mice is an important disease model, in part due to the ability to study genetic manipulations. MRI has been used to assess cardiac structural and functional changes after MI in mice, but changes in myocardial perfusion after acute MI have not previously been examined. Arterial spin labeling noninvasively measures perfusion but is sensitive to respiratory motion and heart rate variability and is difficult to apply after acute MI in mice. To account for these factors, a cardiorespiratory-gated arterial spin labeling sequence using a fuzzy C-means algorithm to retrospectively reconstruct images was developed. Using this method, myocardial perfusion was measured in remote and infarcted regions at 1, 7, 14, and 28 days post-MI. Baseline perfusion was 4.9 6 0.5 mL/gÁmin and 1 day post-MI decreased to 0.9 6 0.8 mL/gÁmin in infarcted myocardium (P < 0.05 versus baseline) while remaining at 5.2 6 0.8 mL/gÁmin in remote myocardium. During the subsequent 28 days, perfusion in the remote zone remained unchanged, while a partial recovery of perfusion in the infarct zone was seen. This technique, when applied to genetically engineered mice, will allow for the investigation of the roles of specific genes in myocardial perfusion during infarct healing. Magn Reson Med 63:648-657, 2010. V C 2010 Wiley-Liss, Inc.Key words: arterial spin labeling; myocardial perfusion; myocardial infarction; fuzzy C-means; mouse Mice are widely used as models of human disease in biomedical research. Similarities in the cardiovascular systems of mice and humans, the low cost of mouse studies, the relative ease of genetic manipulation of mice, and improved surgical techniques have led to increased use of mouse models of myocardial infarction (MI) (1-3). Cardiac MRI has been used to study structural and functional left ventricular (LV) remodeling in mice following MI (3-5). However, measurement of myocardial perfusion in mice by MRI during acute MI and subsequently during the processes of infarct healing and post-MI LV remodeling has not previously been performed.Arterial spin labeling (ASL) provides quantitative measurements of blood flow and has been used for quantification of cerebral blood flow (6,7) and myocardial perfusion (8-11) in humans. In small animals, ASL has been performed in both mice (12-15) and rats (16)(17)(18)(19)(20)(21)(22)(23)(24)(25). Prior murine studies have examined myocardial perfusion at baseline (12-15), with differing anesthesia (13), in response to a vasodilator (13,15), and for phenotyping of genetically altered mice (14,15). Only two prior studies have measured perfusion after MI in mice, and those measurements were restricted only to the remote myocardium at 4 weeks following MI (12,14). ASL has been more widely used in rats (22) and has been used to assess changes in myocardial perfusion in response to dobutamine (17), adenosine (25), methods of anesthesia (23,24), diabetes (18,19) and following coronary stenosis (20,21) and MI (20,21). Similar to mouse studies, measurements...

ObjectiveA number of promising experimental therapies for Duchenne muscular dystrophy (DMD) are emerging. Clinical trials currently rely on invasive biopsies or motivation-dependent functional tests to assess outcome. Quantitative muscle magnetic resonance imaging (MRI) could offer a valuable alternative and permit inclusion of non-ambulant DMD subjects. The aims of our study were to explore the responsiveness of upper-limb MRI muscle-fat measurement as a non-invasive objective endpoint for clinical trials in non-ambulant DMD, and to investigate the relationship of these MRI measures to those of muscle force and function.Methods15 non-ambulant DMD boys (mean age 13.3 y) and 10 age-gender matched healthy controls (mean age 14.6 y) were recruited. 3-Tesla MRI fat-water quantification was used to measure forearm muscle fat transformation in non-ambulant DMD boys compared with healthy controls. DMD boys were assessed at 4 time-points over 12 months, using 3-point Dixon MRI to measure muscle fat-fraction (f.f.). Images from ten forearm muscles were segmented and mean f.f. and cross-sectional area recorded. DMD subjects also underwent comprehensive upper limb function and force evaluation.ResultsOverall mean baseline forearm f.f. was higher in DMD than in healthy controls (p<0.001). A progressive f.f. increase was observed in DMD over 12 months, reaching significance from 6 months (p<0.001, n = 7), accompanied by a significant loss in pinch strength at 6 months (p<0.001, n = 9) and a loss of upper limb function and grip force observed over 12 months (p<0.001, n = 8).ConclusionsThese results support the use of MRI muscle f.f. as a biomarker to monitor disease progression in the upper limb in non-ambulant DMD, with sensitivity adequate to detect group-level change over time intervals practical for use in clinical trials. Clinical validity is supported by the association of the progressive fat transformation of muscle with loss of muscle force and function.

Muscle damage, edema, and fat infiltration are hallmarks of a range of neuromuscular diseases. The T 2 of water, T 2,w , in muscle lengthens with both myocellular damage and inflammation and is typically measured using multiple spin-echo or Carr-Purcell-Meiboom-Gill acquisitions. However, microscopic fat infiltration in neuromuscular diseases prevents accurate T 2,w quantitation as the longer T 2 of fat, T 2,f , masks underlying changes in the water component. Fat saturation can be inconsistent across the imaging volume and removes valuable physiological fat information. A new method is presented that combines iterative decomposition of water and fat with echo asymmetry and least squares estimation with a Carr-Purcell-Meiboom-Gill-sequence. The sequence results in water and fat separated images at each echo time for use in T 2,w and T 2,f quantification. With knowledge of the T 2,w and T 2,f , a T 2 -corrected fat fraction map can also be calculated. Monte-Carlo simulations and measurements in phantoms, volunteers, and a patient with inclusion body myositis are demonstrated. In healthy volunteers, uniform T 2,w and T 2 -corrected fat fraction maps are present within all muscle groups. However, muscle-specific patterns of fat infiltration and edema are evident in inclusion body myositis, which demonstrates the power of separating and quantifying the fat and water components. Magn Reson Med 66:1293-1302, 2011. V C 2011 Wiley Periodicals, Inc.Key words: water-fat separation; T 2 relaxometry; muscular dystrophy; edema Neuromuscular diseases commonly involve a range of skeletal muscle pathologies including inflammation, muscle wasting, and fat infiltration (1,2). As the molecular and genetic basis of many of these diseases becomes increasingly understood, there is a need for reliable methods to sensitively monitor disease progression and response to new treatments. For example, gene therapies have shown promise in the potential treatment of the disabling and eventually fatal condition Duchenne muscular dystrophy (3,4).MRI is emerging as a suitable method to monitor neuromuscular disease due to its sensitivity to key processes in the diseased muscle such as edema and fat infiltration (5,6). In contrast to muscle biopsy, which currently provides an established indicator of disease, MRI offers a repeatable, noninvasive, whole-organ approach for use in longitudinal clinical trials. Furthermore, MRI can quantify physical properties such as T 2 relaxation times and fat fractions within affected muscles.The T 2 of skeletal muscle increases with both damage and edema (7-9). Together, these ''edema-like'' regions appear bright on T 2 weighted imaging. In mouse models of limb girdle muscular dystrophy, T 2 values are elevated relative to controls, although following gene therapy T 2 values return to near-control levels (10). T 2 measurements in mouse models are simplified by the lack of fat infiltration that hallmarks these diseases in human patients. In humans, invasive replacement of muscle fibers in dystrophic muscle by fa...

Atherosclerosis is a complex disease whose spatial distribution is hypothesized to be influenced by the local hemodynamic environment. The use of transgenic mice provides a mechanism to study the relationship between hemodynamic forces, most notably wall shear stress (WSS), and the molecular factors that influence the disease process. Phase contrast MRI using rectilinear trajectories has been used to measure boundary conditions for use in computational fluid dynamic models. However, the unique flow environment of the mouse precludes use of standard imaging techniques in complex, curved flow regions such as the aortic arch. In this article, two‐dimensional and three‐dimensional spiral cine phase contrast sequences are presented that enable measurement of velocity profiles in curved regions of the mouse vasculature. WSS is calculated directly from the spatial velocity gradient, enabling WSS calculation with a minimal set of assumptions. In contrast to the outer radius of the aortic arch, the inner radius has a lower time‐averaged longitudinal WSS (7.06 ± 0.76 dyne/cm2 vs. 18.86 ± 1.27 dyne/cm2; P < 0.01) and higher oscillatory shear index (0.14 ± 0.01 vs. 0.08 ± 0.01; P < 0.01). This finding is in agreement with humans, where WSS is lower and more oscillatory along the inner radius, an atheroprone region, than the outer radius, an atheroprotective region. Magn Reson Med, 2011. © 2011 Wiley Periodicals, Inc.