Patrick A. Helm

Postinfarction Myocardial Scarring in Mice: Molecular MR Imaging with Use of a Collagen-targeting Contrast Agent

PURPOSE To prospectively evaluate a gadolinium-based collagen-targeting contrast agent, EP-3533, for in vivo magnetic resonance (MR) imaging of myocardial fibrosis in a mouse model of healed myocardial infarction (MI). MATERIALS AND METHODS All procedures were performed in accordance with protocols approved by the animal care and use committee. MI was induced in eight mice by means of occlusion of the left anterior descending coronary artery followed by reperfusion. Four MR examinations were performed in each animal: one examination before, one examination 1 day after, and two examinations 6 weeks after the MI. For the latter two examinations, electrocardiographically gated inversion-recovery gradient-echo MR images were acquired before and serially (every 5 minutes) after the intravenous injection of either gadopentetate dimeglumine or EP-3533. The image enhancement kinetic properties of the postinfarction scar, normal myocardium, and blood were compared. RESULTS Dynamic T1-weighted MR imaging revealed the washout time constants for EP-3533 to be significantly longer than those for gadopentetate dimeglumine in regions of postinfarction scarring (mean, 194.8 minutes +/-116.8 [standard deviation] vs 25.5 minutes +/- 4.2; P < .05) and in normal myocardium (mean, 45.4 minutes +/- 16.7 vs 25.1 minutes +/- 9.7; P < .05). Findings on postmortem histologic sections stained for collagen correlated well with EP-3533-enhanced areas seen on inversion-recovery MR images. Fifty minutes after EP-3533 injection, the postinfarction scar tissue samples, as compared with the normal myocardium, had a twofold higher concentration of gadolinium. CONCLUSION Use of the gadolinium-based collagen-targeting contrast agent, EP-3533, enabled in vivo molecular MR imaging of fibrosis in a mouse model of healed postinfarction myocardial scarring.

Imaging Two-Dimensional Displacements and Strains in Skeletal Muscle during Joint Motion by Cine DENSE MR

The objective of this study was to apply cine magnetic resonance imaging (MRI) using displacement encoding with stimulated echoes (DENSE) to measure the dynamic two-dimensional (2D) displacement and Lagrangian strain fields in the biceps brachii muscle. Six healthy volunteers underwent cine DENSE MRI during repeated elbow flexion against the load of gravity. Displacement encoded dynamic images of the upper arm were acquired with spatial and temporal resolutions of 1.9 x 1.9 mm(2) and 30 ms, respectively. Pixel-wise Lagrangian displacement and strain fields were calculated from the measured images. We extracted the first and second principal strains (E1 and E2) along the centerline and anterior regions of the muscle. E1 and E2 were relatively uniform along the anterior region. However, E1 and E2 were both non-uniform along the centerline region-normalized values for E1 and E2 varied over the ranges of 0.27-1.35, and 0.45-2.36, respectively. The directions of the first and second principal strains varied throughout the muscle and showed that the direction of principal shortening is not necessarily aligned with fascicle direction. This study demonstrates the utility of cine DENSE MRI for analyzing skeletal muscle mechanics and provides data describing the in vivo mechanics of muscle tissue to a level of detail that has not been previously possible.

Balanced multipoint displacement encoding for DENSE MRI.

Displacement encoding with stimulated echoes (DENSE) is a quantitative imaging technique that encodes tissue displacement in the phase of the acquired signal. Various DENSE sequences have encoded displacement using methods analogous to the simple multipoint methods of phase contrast (PC) MRI. We developed general n‐dimension balanced multipoint encoding for DENSE. Using these methods, phase noise variance decreased experimentally by 73.7%, 65.6%, and 61.9% compared with simple methods, which closely matched the theoretical decreases of 75%, 66.7%, and 62.5% for one‐dimensional (1D), 2D, and 3D encoding, respectively. Phase noise covariances decreased by 99.2% and 99.3% for balanced 2D and 3D encoding, consistent with the zero‐covariance prediction. The direction bias inherent to the simple methods was decreased to almost zero using balanced methods. Reduced phase noise and improved displacement and strain maps using balanced methods were visually observed in phantom and volunteer images. Balanced multipoint encoding can also be applied to PC MRI. Magn Reson Med, 2009.

Spinal Navigation and Imaging: History, Trends, and Future

The clinical practice of spine navigation has rapidly grown with the development of image-based guidance. In this paper, a brief history of spinal navigation is presented and a review of clinical outcomes for pedicle screws placed using the latest technology in the sacral, lumbar and thoracic regions. The clinical evidence demonstrate that intraoperative 3D image guided surgery has a 96.8% success rate. A concluding section detailing existing barriers that limit more widespread adoption and future development efforts is presented.

Wall-Motion Based Analysis of Global and Regional Left Atrial Mechanics

Atrial fibrillation is an increasingly prevalent cardiovascular disease; changes in atrial structure and function induced by atrial fibrillation and its treatments are often spatially heterogeneous. However, spatial heterogeneity of function is difficult to assess with standard imaging techniques. This paper describes a method to assess global and regional mechanical function by combining cardiac magnetic resonance imaging and finite-element surface fitting. We used this fitted surface to derive measures of left atrial volume, regional motion, and spatial heterogeneity of motion in 23 subjects, including healthy volunteers and atrial fibrillation patients. We fit the surfaces using a Newton optimization scheme in under 1 min on a standard laptop, with a root mean square error of 2.3±0.5 mm, less than 9% of the mean fitted radius, and an inter-operator variability of less than 10%. Fitted surfaces showed clear definition of the phases of left atrial motion (filling, passive emptying, active contraction) in both volume-time and regional radius-time curves. Averaged surfaces of healthy volunteers and atrial fibrillation patients provided evidence of substantial regional variation in both amount and timing of regional motion, indicating spatial heterogeneity of function, even in healthy adults.

A four-dimensional model-based method for assessing cardiac contractile dyssynchrony in mice

Four-dimensional (4D), or equivalently, 3D + time, analysis is useful for comprehensive assessment cardiac function, especially in the asymmetric left ventricle (LV) after myocardial infarction (MI). This paper presents a 4D-model-based method for ultrasound assessment of cardiac contractile function in mice. Echocardiographic image sequences were acquired at high frequency (30 MHz) from the hearts of C57Bl/6 mice. Image sequences were acquired at contiguous slice locations encompassing the entire 3D LV. In order to reconstruct continuous, dynamic 3D LVs from the images using a 4D mathematical cardiac model, endocardial and epicardial contours were segmented for all image slice locations through one cardiac cycle. In the 4D model, shape and continuity constraints were applied in order to normalize irregularities caused by noise or non-uniform distribution of image data. Root mean square error (RMSE) was calculated between the model-fitted 4D LV and the actual LV surface measured from image data. RMSE was 0.23 mm (~4.5% of epicardial diameter) for the epicardial surface, and 0.20 mm (6.4% of endocardial diameter) for the endocardial surface. 3D regional wall thickening was calculated from the 4D LV surface, and LV dyssynchrony was assessed by analyzing the time to peak strain (Tpeak). This 3D analysis of contractile function in post-MI mouse hearts revealed >80% reduction of peak radial displacement, a 10-15 ms delay in Tpeak in the infarct zone, and a SD_Tpeak of 6-10 ms over the entire 3D LV. In summary, the 4D-model-based method was successfully used for analyzing cardiac dyssynchrony in the 3D murine LV, and it proved advantageous over conventional 2D methods because it was more comprehensive and noise-robust.

Quantification of global and regional left atrial function in paroxysmal atrial fibrillation using CMR derived 4-D wall motion analysis

Methods Eight healthy volunteers (6 male, mean 29.7 yrs) and 6 patients (6 male, mean 61.7 yrs) with paroxysmal AF underwent imaging during sinus rhythm on a 1.5 T scanner. Steady state free procession imaging of the LA, acquired in an axial stack and parasagittal at 6 mm slice thickness with no interslice gap, was retrospectively reconstructed into 25 phases per R-R interval. Segmentation of the LA wall was performed manually using ARGUS software (Siemens Medical Solutions). The following landmarks were identified manually at each phase and used to construct a spherical coordinate system: four pulmonary vein ostia and four points on the mitral annulus (superior, inferior, left, right). Using MATLAB, contour points were fitted with a 16-element mesh to obtain a continuous description of changes in atrial radius through space and time. LA volume and radial fractional shortening of each element were calculated for each phase and subject. Elements were separated into superior, inferior, septal and free walls for regional analysis. Differences between patients and volunteers were determined with an unpaired t-test.

2091 Manganese enhanced mri demonstrates a predominant role for nNOS, not eNOS, in modulating L-Type calcium channel flux in the heart

Introduction Modulation of L-Type Calcium Channel (LTCC) flux plays an important role in calcium cycling and contractility. Based upon localization within the cardiomyocyte, prevailing opinion is that neuronal nitric oxide synthase (nNOS) modulates sarcoplasmic reticular calcium release, while endothelial NOS (eNOS) modulates LTCC flux. Counter to this hypothesis, a recent in vitro study suggests that nNOS modulates LTCC flux. Since Mn2+ enters the myocyte through the LTCC in proportion to Ca2+ flux and shortens T1, Mn-enhanced MRI may be used to probe in vivo LTCC flux.