Collagenase treatment reduces the anisotropy of ultrasonic backscatter in rat myocardium by reducing collagen crosslinks.

Dysregulation of collagen deposition, degradation, and crosslinking in the heart occur in response to increased physiological stress. Collagen content has been associated with ultrasonic backscatter (brightness), and we have shown that the anisotropy of backscatter can be used to measure myofiber alignment, that is, variation in the brightness of a left ventricular short-axis ultrasound. This study investigated collagen's role in anisotropy of ultrasonic backscatter; female Sprague-Dawley rat hearts were treated with a collagenase-containing solution, for either 10 or 30 min, or control solution for 30 min. Serial ultrasound images were acquired at 2.5-min intervals throughout collagenase treatment. Ultrasonic backscatter was assessed from anterior and posterior walls, where collagen fibrils are predominately aligned perpendicular to the angle of insonification, and the lateral and septal walls, where collagen is predominately aligned parallel to the angle of insonification. Collagenase digestion reduced backscatter anisotropy within the myocardium. Collagen remains present in the myocardium throughout collagenase treatment, but crosslinking is altered within 10 min. These data suggest that crosslinking of collagen modulates the anisotropy of ultrasonic backscatter. An Anisotropy Index, derived from differences in backscatter from parallel and perpendicularly aligned fibers, may provide a noninvasive index to monitor the progression and state of myocardial fibrosis.

Myocardial Fiber Mapping of Rat Hearts, Using Apparent Backscatter, with Histologic Validation.

Myocardial fiber architecture is a physiologically important regulator of ejection fraction, strain and pressure development. Apparent ultrasonic backscatter has been shown to be a useful method for recreating the myocardial fiber architecture in human-sized sheep hearts because of the dependence of its amplitude on the relative orientation of a myofiber to the angle of ultrasonic insonification. Thus, the anisotropy of the backscatter signal is linked to and provides information about the fiber orientation. In this study, we sought to determine whether apparent backscatter could be used to measure myofiber orientation in rodent hearts. Fixed adult-rat hearts were imaged intact, and both a transmural cylindrical core and transmural wedge of the left ventricular free wall were imaged. Cylindrical core samples confirmed that backscatter anisotropy could be measured in rat hearts. Ultrasound and histologic analysis of transmural myocardial wedge samples confirmed that the apparent backscatter could be reproducibly mapped to fiber orientation (angle of the fiber relative to the direction of insonification). These data provided a quantitative relationship between the apparent backscatter and fiber angle that was applied to whole-heart images. Myocardial fiber architecture was successfully measured in rat hearts. Quantifying myocardial fiber architecture, using apparent backscatter, provides a number of advantages, including its scalable use from rodents to man, its rapid low-cost acquisition and minimal contraindications. The method outlined in this study provides a method for investigators to begin detailed assessments of how the myocardial fiber architecture changes in preclinical disease models, which can be immediately translated into the clinic.

Toward 3-D Echocardiographic Determination of Regional Myofiber Structure.

As a step toward the goal of relating changes in underlying myocardial structure to observed altered cardiac function in the hearts of individual patients, this study addresses the feasibility of creating echocardiography-derived maps of regional myocardial fiber structure for entire, intact, excised sheep hearts. Backscatter data were obtained from apical echocardiographic images acquired with a clinical ultrasonic imaging system and used to determine local fiber orientations in each of seven hearts. Systematic acquisition across the entire heart volume provided information sufficient to give a complete map for each heart. Results from the echocardiography-derived fiber maps compare favorably with corresponding results derived from diffusion tensor magnetic resonance imaging. The results of this study provide evidence of the feasibility of using echocardiographic methods to generate individualized whole heart fiber maps for patients.

Echocardiographic-based assessment of myocardial fiber structure in individual, excised hearts.

The objective of this study was to assess the feasibility of using echocardiographic imaging as an approach for determining the myocardial fiber structure of intact, individual hearts. Seven formalin-fixed, ex vivo sheep hearts were imaged using a commercially available echocardiographic imaging system, and the intrinsic fiber structure for the reconstructed short-axis cross section was determined for a specific distance from the apex of each heart. Diffusion tensor magnetic resonance (DT-MR) images of each heart were acquired and fiber maps were created for comparison with the fiber structure obtained from the corresponding reconstructed echocardiographic images. These two methods of obtaining the fiber structure showed relatively good agreement, suggesting that measurements of fiber orientation for individual hearts can be derived from echocardiographic images. Further development of this method may provide a clinically useful approach for mapping the fiber orientation in individual patients over the heart cycle.

Imaging of Her2-targeted magnetic nanoparticles for breast cancer detection: comparison of SQUID-detected magnetic relaxometry and MRI.

Both magnetic relaxometry and magnetic resonance imaging (MRI) can be used to detect and locate targeted magnetic nanoparticles, noninvasively and without ionizing radiation. Magnetic relaxometry offers advantages in terms of its specificity (only nanoparticles are detected) and the linear dependence of the relaxometry signal on the number of nanoparticles present. In this study, detection of single-core iron oxide nanoparticles by superconducting quantum interference device (SQUID)-detected magnetic relaxometry and standard 4.7 T MRI are compared. The nanoparticles were conjugated to a Her2 monoclonal antibody and targeted to Her2-expressing MCF7/Her2-18 (breast cancer cells); binding of the nanoparticles to the cells was assessed by magnetic relaxometry and iron assay. The same nanoparticle-labeled cells, serially diluted, were used to assess the detection limits and MR relaxivities. The detection limit of magnetic relaxometry was 125 000 nanoparticle-labeled cells at 3 cm from the SQUID sensors. T(2)-weighted MRI yielded a detection limit of 15 600 cells in a 150 µl volume, with r(1) = 1.1 mm(-1) s(-1) and r(2) = 166 mm(-1) s(-1). Her2-targeted nanoparticles were directly injected into xenograft MCF7/Her2-18 tumors in nude mice, and magnetic relaxometry imaging and 4.7 T MRI were performed, enabling direct comparison of the two techniques. Co-registration of relaxometry images and MRI of mice resulted in good agreement. A method for obtaining accurate quantification of microgram quantities of iron in the tumors and liver by relaxometry was also demonstrated. These results demonstrate the potential of SQUID-detected magnetic relaxometry imaging for the specific detection of breast cancer and the monitoring of magnetic nanoparticle-based therapies.

Multi-exponential signal decay from diffusion in a single compartment.

Multi-exponential decays in diffusion experiments are typically fitted to sums of exponentially decaying components; often this is taken as evidence for spins in multiple distinct compartments. Here we examine the signal decay due to diffusion in a single cylinder, for short diffusion times (lightly restricted). The signals are well-modeled by a sum of two exponentials, despite the single compartment housing the spins. The results agree with a previous theoretical examination of the problem. The implication for biological systems is that multiple decay signal components may not correspond to multiple physical compartments.