The relative distribution of membranous and cytoplasmic met is a prognostic indicator in stage I and II colon cancer.

PURPOSE: The association hepatocyte growth factor receptor (Met) tyrosine kinase with prognosis and survival in colon cancer is unclear, due in part to the limitation of detection methods used. In particular, conventional chromagenic immunohistochemistry (IHC) has several limitations including the inability to separate compartmental measurements. Measurement of membrane, cytoplasm, and nuclear levels of Met could offer a superior approach to traditional IHC. EXPERIMENTAL DESIGN: Fluorescent-based IHC for Met was done in 583 colon cancer patients in a tissue microarray format. Using curvature and intensity-based image analysis, the membrane, nuclear, and cytoplasm were segmented. Probability distributions of Met within each compartment were determined, and an automated scoring algorithm was generated. An optimal score cutpoint was calculated using 500-fold crossvalidation of a training and test data set. For comparison with conventional IHC, a second array from the same tissue microarray block was 3,3'-diaminobenzidine immunostained for Met. RESULTS: In crossvalidated and univariate Cox analysis, the membrane relative to cytoplasm Met score was a significant predictor of survival in stage I (hazard ratio, 0.16; P = 0.006) and in stage II patients (hazard ratio, 0.34; P < or = 0.0005). Similar results were found with multivariate analysis. Met in the membrane alone was not a significant predictor of outcome in all patients or within stage. In the 3,3'-diaminobenzidine-stained array, no associations were found with Met expression and survival. CONCLUSIONS: These data indicate that the relative subcellular distribution of Met, as measured by novel automated image analysis, may be a valuable biomarker for estimating colon cancer prognosis.

Toward single breath-hold whole-heart coverage coronary MRA using highly accelerated parallel imaging with a 32-channel MR system.

Coronary MR angiography (CMRA) is generally confined to the acquisition of multiple targeted slabs with coverage dictated by the competing constraints of signal-to-noise ratio (SNR), physiological motion, and scan time. This work addresses these obstacles by demonstrating the technical feasibility of using a 32-channel coil array and receiver system for highly accelerated volumetric breath-hold CMRA. The use of the 32-element array in unaccelerated CMRA studies provided a baseline SNR increase of as much as 40% over conventional cardiac-optimized phased array coils, which resulted in substantially enhanced image quality and improved delineation of the coronary arteries. Modest accelerations were used to reduce breath-hold durations for tailored coverage of the coronary arteries using targeted multi-oblique slabs to as little as 10 s. Finally, high net accelerations were combined with the SNR advantages of a 3D steady-state free precession (SSFP) technique to achieve previously unattainable comprehensive volumetric coverage of the coronary arteries in a single breath-hold. The merits and limitations of this simplified volumetric imaging approach are discussed and its implications for coronary MRA are considered.

32-element receiver-coil array for cardiac imaging.

A lightweight 32-element MRI receiver-coil array was designed and built for cardiac imaging. It comprises an anterior array of 21 copper rings (75 mm diameter) and a posterior array of 11 rings (107 mm diameter) that are arranged in hexagonal lattices so as to decouple nearest neighbors, and curved around the left side of the torso. Imaging experiments on phantoms and human volunteers show that it yields superior performance relative to an eight-element cardiac array as well as a 32-element whole-torso array for both traditional nonaccelerated cardiac imaging and 3D parallel imaging with acceleration factors as high as 16.

Short breath-hold, volumetric coronary MR angiography employing steady-state free precession in conjunction with parallel imaging.

An ECG-gated, 3D steady-state free precession (SSFP) technique in conjunction with sensitivity encoding (SENSE)-based parallel imaging was implemented for short breath-hold, volumetric coronary MR angiograpy (CMRA). Two parallel imaging acquisition strategies (employing 1 R-R and 2 R-R intervals, respectively) were developed to achieve 1) very short breath-hold times (12 s for a heart rate of 60 bpm), and 2) small acquisition windows to minimize sensitivity to physiologic motion. Both strategies were examined in CMRA applications over a range of heart rates. A four-point scale blinded reading (with 4 indicating the most desirable features) revealed substantial image quality improvements for the accelerated data as compared to the nonaccelerated approach. The 1 R-R interval scheme yielded an image score of 3.39 +/- 0.60, and was found to be particularly suitable for low heart rates (P = 0.0008). The 2 R-R interval strategy yielded an image score of 3.35 +/- 0.64, and was more appropriate for higher heart rates (P = 0.03). The results demonstrate that 3D SSFP combined with parallel imaging is a versatile method for short breath-hold CMRA while maintaining high spatial resolution. This strategy permits imaging of the major coronary artery distributions in two to three breath-holds using targeted slabs, and offers the potential for single breath-hold, large-volume CMRA.

Radiofrequency power deposition utilizing thermal imaging.

Wavelength effects influence radiofrequency (RF) power deposition distributions and limit magnetic resonance (MR) medical applications at very high magnetic fields. The power depositions in spherical saline gel phantoms were deduced from proton resonance shift thermal maps at both 1.5 T and 3.0 T over a range of conductivities. Phase differences before and after RF heating were measured for both a quadrature head coil and a circular surface coil. A long echo time (TE) pulse sequence with a 3D phase unwrap algorithm provided increased thermal sensitivity. The measured thermal maps agreed with a model of eddy-current heating by circularly polarized oscillating RF fields in a conducting dielectric sphere. At 3.0 T, thermal maps were acquired with a <0.32 degrees C temperature rise at 4 W. Proton resonance shift thermal maps provided a measure of hot spots in very-high-field MR imaging (MRI), in which both the phase sensitivity and signal-to-noise ratio (SNR) were increased. The method provides a means of studying the heat distribution generated by RF coils excited by clinical pulse sequences.

Conformation and structure of polymeric contrast agents for medical imaging.

The structure of Gd-DTPA-polylysine, Gd-DOTA-polylysine, Gd-SCN-Bz-DOTA-polylysine, and Gd-DTPA-poly(glu:lys) was investigated with circular dichroism, gel permeation chromatography, low angle light scattering, and proton longitudinal relaxivity. Molecular modeling calculations were performed and predicted helical secondary structure for charged Gd-chelator residues, i.e., Gd-DTPA, when the DTPA conjugation levels reached 90% and higher. This helical secondary structure was observed with circular dichroism. The conformational transition from coiled to extended linear was observed also by gel permeation chromatography and by proton relaxivity measurements. The helical secondary structure was not observed when the chelator was changed to DOTA. The residue charge interactions were eliminated in this case since the Gd-DOTA complex had no net charge. For this construct, the gel permeation and relaxivity measurements indicated a coiled conformation. An extended linear conformation was regained when the chelator complex was changed to Gd-SCN-Bz-DOTA, which had a net negative charge. The functional aspects of these structures were investigated by MR imaging of an animal tumor model. The linear extended polymer constructs gave 10-fold higher tumor signals then the coiled-collapsed constructs, indicating a much higher degree of trans-endothelial transport in the tumors.