Biomedical subjects

A Z Faranesh

Publications and source records attributed to A Z Faranesh.

6 recordsLinked to original sources

PubMed2012

MRI roadmap-guided transendocardial delivery of exon-skipping recombinant adeno-associated virus restores dystrophin expression in a canine model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) cardiomyopathy patients currently have no therapeutic options. We evaluated catheter-based transendocardial delivery of a recombinant adeno-associated virus (rAAV) expressing a small nuclear U7 RNA (U7smOPT) complementary to specific cis-acting splicing signals. Eliminating specific exons restores the open reading frame resulting in translation of truncated dystrophin protein. To test this approach in a clinically relevant DMD model, golden retriever muscular dystrophy (GRMD) dogs received serotype 6 rAAV-U7smOPT via the intracoronary or transendocardial route. Transendocardial injections were administered with an injection-tipped catheter and fluoroscopic guidance using X-ray fused with magnetic resonance imaging (XFM) roadmaps. Three months after treatment, tissues were analyzed for DNA, RNA, dystrophin protein, and histology. Whereas intracoronary delivery did not result in effective transduction, transendocardial injections, XFM guidance, enabled 30±10 non-overlapping injections per animal. Vector DNA was detectable in all samples tested and ranged from <1 to >3000 vector genome copies per cell. RNA analysis, western blot analysis, and immunohistology demonstrated extensive expression of skipped RNA and dystrophin protein in the treated myocardium. Left ventricular function remained unchanged over a 3-month follow-up. These results demonstrated that effective transendocardial delivery of rAAV-U7smOPT was achieved using XFM. This approach restores an open reading frame for dystrophin in affected dogs and has potential clinical utility.

Animals↗

PubMed2000

Ultrafast pulse sequence techniques for cardiac magnetic resonance imaging.

Cardiac magnetic resonance imaging is a rapidly emerging field that has seen tremendous advances in the past decade. Central to the development of effective imaging strategies has been the advent of high-performance gradient hardware and the exploitation of their speed characteristics through specialized pulse sequences well suited for cardiac imaging. These advances have facilitated unprecedented acquisition times that now approach echocardiographic frame rates, while maintaining excellent image quality. This article provides a detailed overview of advanced pulse sequence technology and approaches currently taken to maximize speed performance and image quality. In particular, segmented K-space techniques that include single-echo and multiecho spoiled gradient-echo imaging as well as steady-state free precession imaging are discussed. Finally, spiral and fast spin-echo techniques are explored. Examples of common applications of these pulse sequences are presented.

Echo-Planar Imaging↗

PubMed1999

A novel object-independent "balanced" reference scan for echo-planar imaging.

Interleaved echo-planar imaging (EPI) is susceptible to significant ghosting artifacts, resulting primarily from system time delays that cause data matrix misregistration. Most EPI applications rely on "reference scans" to measure delays, and post-processing algorithms are used to correct these errors. Unfortunately, delay estimates made with most reference scan techniques are object dependent, since they are biased by magnetic field inhomogeneities and chemical shift. The current work describes the effects of field inhomogeneities and their influence on system time delay estimation. Subsequently, a new, object-independent "balanced" reference method using two readout echo trains is proposed for time delay measurements.

Algorithms↗

PubMed1999

Referenceless interleaved echo-planar imaging.

Interleaved echo-planar imaging (EPI) is an ultrafast imaging technique important for applications that require high time resolution or short total acquisition times. Unfortunately, EPI is prone to significant ghosting artifacts, resulting primarily from system time delays that cause data matrix misregistration. In this work, it is shown mathematically and experimentally that system time delays are orientation dependent, resulting from anisotropic physical gradient delays. This analysis characterizes the behavior of time delays in oblique coordinates, and a new ghosting artifact caused by anisotropic delays is described. "Compensation blips" are proposed for time delay correction. These blips are shown to remove the effects of anisotropic gradient delays, eliminating the need for repeated reference scans and postprocessing corrections. Examples of phantom and in vivo images are shown.

Algorithms↗

PubMed1999

Multi-echo segmented k-space imaging: an optimized hybrid sequence for ultrafast cardiac imaging.

Cardiac magnetic resonance imaging requires high temporal resolution to resolve motion and contrast uptake with low total scan times to avoid breathing artifacts. While spoiled gradient echo (SPGR) imaging is robust and reproducible, it is relatively inefficient and requires long breath-holds to acquire high time resolution movies of the heart. Echo planar imaging (EPI) is highly efficient with excellent signal-to-noise ratio (SNR) behavior; however, it is particularly difficult to use in the heart because of its sensitivity to chemical shift, susceptibility, and motion. EPI may also require reference scans, which are used to measure hardware delays and phase offsets that cause ghosting artifacts; these reference scans are more difficult and less reliable in the heart. Consequently, a hybrid EPI/SPGR sequence is proposed for application to rapid cardiac imaging. A detailed optimization of SNR and echo train length for multi-echo sequences is presented. It is shown that significant reductions in total scan time are possible while maintaining good image quality. This will allow complete motion sampling of the entire heart in one to three breath-holds, necessary for MR cardiac dobutamine stress testing. Improved speed performance also permits sampling of three to six slices every heartbeat for bolus injection perfusion studies.

Echo-Planar Imaging↗

PubMed1998

In vivo measurement of T*2 and field inhomogeneity maps in the human heart at 1.5 T.

Cardiac echo-planar imaging suffers invariably from regions of severe distortion and T*2 decay in the myocardium. The purpose of this work was to perform local measurements of T*2 and field inhomogeneities in the myocardium and to identify the sources of focal signal loss and distortion. Field inhomogeneity maps and T*2 were measured in five normal volunteers in short-axis slices spanning from base to apex. It was found that T*2 ranged from 26 ms (SD = 7 ms, n = 5) to 41 ms (SD = 11 ms, n = 5) over most of the heart, and peak-to-peak field inhomogeneity differences were 71 Hz (SD = 14 Hz, n = 5). In all hearts, regions of severe signal loss were consistently adjacent to the posterior vein of the left ventricle; T*2 in these regions was 12 ms (SD = 2 ms, n = 5), and the difference in resonance frequency with the surrounding myocardium was 70-100 Hz. These effects may be caused by increased magnetic susceptibility from deoxygenated blood in these veins.

Artifacts↗