Biomedical subjects

Chris A Flask

Publications and source records attributed to Chris A Flask.

4 recordsLinked to original sources

PubMed2006

The mTOR pathway is regulated by polycystin-1, and its inhibition reverses renal cystogenesis in polycystic kidney disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is a common genetic disorder that frequently leads to renal failure. Mutations in polycystin-1 (PC1) underlie most cases of ADPKD, but the function of PC1 has remained poorly understood. No preventive treatment for this disease is available. Here, we show that the cytoplasmic tail of PC1 interacts with tuberin, and the mTOR pathway is inappropriately activated in cyst-lining epithelial cells in human ADPKD patients and mouse models. Rapamycin, an inhibitor of mTOR, is highly effective in reducing renal cystogenesis in two independent mouse models of PKD. Treatment of human ADPKD transplant-recipient patients with rapamycin results in a significant reduction in native polycystic kidney size. These results indicate that PC1 has an important function in the regulation of the mTOR pathway and that this pathway provides a target for medical therapy of ADPKD.

Animals↗

PubMed2006

Blood attenuation with SSFP-compatible saturation (BASS).

PURPOSE: To investigate a rapid flow-suppression method for improving the contrast-to-noise ratio (CNR) between the vessel wall and the lumen for cardiovascular imaging applications. MATERIALS AND METHODS: In this study a new dark-blood steady-state free precession (SSFP) sequence utilizing two excitation pulses per TR was developed. The first pulse is applied immediately adjacent to the slice of interest, while the second is a conventional slice-selective pulse designed to excite an SSFP signal for the static spins in the slice of interest. The slice-selective pulse is followed by fully refocused gradients along all three imaging axes over each TR. The signal amplitude (SA) from the moving spins excited by the "saturation" pulse is attenuated since they are not fully refocused at the TE. RESULTS: This work provides confirmation, by both simulation and experiments, that modest adaptations of the basic True-FISP structure can limit unwanted "bright blood" signal within the vessels while simultaneously preserving the contrast and speed advantages of this well-established rapid imaging method. CONCLUSION: Animal imaging trials confirm that dark-blood contrast is achieved with the BASS sequence, which substantially reverses the lumen-to-muscle CNR of a conventional True-FISP "bright blood" acquisition from 14.77 (bright blood) to -13.96 (dark blood) with a modest increase (24.2% of regular TR of SSFP for this implementation) in acquisition time to accommodate the additional slab-selective excitation pulse and gradient pulses.

Animals↗

PubMed2003

Keyhole Dixon method for faster, perceptually equivalent fat suppression.

PURPOSE: To reduce the acquisition time associated with the two-point Dixon fat suppression technique by combining a keyhole in-phase (Water + Fat) k-space data set with a full out-of-phase (Water - Fat) k-space data set and optimizing the keyhole size with a perceptual difference model. MATERIALS AND METHODS: A set of keyhole Dixon images was created by varying the number of lines in the keyhole data set. Off-resonance correction was incorporated into the image reconstruction process to improve the homogeneity of the fat suppression. A perceptual difference model (PDM) was validated with human observer experiments and used to compare the keyhole images to images from a full two-point Dixon acquisition. The PDM was used to determine the smallest keyhole width required to obtain perceptual equivalence to images obtained from the full two-point Dixon method. RESULTS: In experimental phantom studies, the keyhole Dixon image reconstructed from 96 of 192 Water + Fat k-space lines and 192 Water - Fat k-space lines was perceptually equivalent to the full (192 + 192) two-point Dixon images, resulting in a 25% reduction in scan time. Clinical images of a volunteer's knee, orbits, and abdomen created from the smallest, perceptually equivalent keyhole width resulted in a 27%-38% reduction in total scan time. CONCLUSION: This method improves the temporal efficiency of the conventional two-point Dixon technique and may prove especially useful for high-field systems where specific absorption rate (SAR) limits will constrain radiofrequency (RF)-based fat suppression techniques.

Adipose Tissue↗

PubMed2003

Radial alternating TE sequence for faster fat suppression.

This study describes a steady-state sequence that uses a radial k-space trajectory and alternating echo times (TEs) between even and odd k-space views. The sequence generated a single data set that was used to reconstruct images with inherent fat suppression. This fat suppression results from the fat phase variation in alternate echoes giving rise to cancellation in the central portion of k-space. This new fat-suppression method provides inherent fat suppression in half the acquisition time relative to the radial two-point Dixon method. The improvement in k-space sampling efficiency is demonstrated in phantom and clinical images, and through measured point-spread functions (PSFs). As a result, the radial alternating TE sequence offers improved temporal resolution over a radial version of the two-point Dixon sequence by requiring fewer total projections to obtain the same effective resolution in water-based tissues.

Adipose Tissue↗