Andrew L. Alexander

A new nonionic macrocyclic gadolinium(III) chelate as a potential magnetic-resonance-imaging contrast agent

A new GdIII complex of a 17-membered macrocycle with three pendant carboxymethyl groups has been synthesized; the ligand has been obtained in a single step from diethylenetriaminepentaacetic dianhydride (pentetic dianhydride) and 1,4-butanediamine (putrescine). An X-ray crystal analysis has shown that the complex is a nonionic metal chelate with a coordinated water molecule. The near-zero electrical conductivity, 1 omega-1 cm2 mol-1, of a 1 mM solution indicated that the metal chelate is essentially undissociated. The NMR T1 relaxivity is 2.5 s-1 mM-1 at a resonance field of 64 MHz, and 3.4 s-1 mM-1 at 250 MHz. This new GdIII complex is a potentially important magnetic resonance imaging contrast agent.

Comparison of illumination wavelengths for detection of atherosclerosis by optical fluorescence spectroscopy

Illumination wavelengths between 270 and 470 nm are evaluated to determine which wavelength produces the greatest difference between the fluorescence emission spectra of normal and atheromatous arterial tissues. Atherosclerotic plaques are considered as a diseased class and are further subdivided into three diseased subclasses-fibrous plaques, complicated plaques, and hard calcified plaques. The Mahalanobis distance squared, a statistical figure of merit describing class separability, is used to compare the illumination wavelengths. Classification accuracies are also estimated and used for comparison. Optimum classification performance is found to occur with illumination in the wavelength range 314 to 334 nm, except for hard calcified plaques, which are more accurately classified with illumination wavelengths longer than 380 nm. The issue of how much information is required from the fluorescence emission spectra to accurately classify tissue is also investigated.

Magnetic resonance guidance of percutaneous ethanol injection in liver

RATIONALE AND OBJECTIVES Percutaneous ethanol injection (PEI) is used as a form of treatment for cancer, particularly malignant hepatic tumors. Little is known about the intratumoral distributions of ethanol following PEI. We assessed, using magnetic resonance (MR) imaging, the distribution of ethanol in liver and the concentration of ethanol needed to kill tumor cells in vivo. METHODS MR imaging studies were performed using phantoms of alcohol, ex vivo bovine liver, and healthy human volunteers. A variety of pulse sequences were tested for their ability to maximize the signal intensity from alcohol while minimizing the signal from liver tissues as well as the regions of necrosis following ethanol injection. A cell culture model of in vitro cytotoxicity was developed to predict the target concentration of alcohol necessary for killing tumor cells. RESULTS At 1.5 T, we found that an inversion-recovery spin-echo sequence using an inversion time of 250 msec and an echo time of 150 msec in combination with water saturation pulses effectively suppressed the tissue water signal from human liver while obtaining a clear signal from the ethanol. The cytotoxicity experiments suggested that a concentration of 20% or more ethanol is sufficient to completely kill all the tumor cells. CONCLUSION A critical concentration of ethanol (e.g., 10%) is necessary for full tumoricidal effect. MR imaging should be able to determine the volume of distribution and the intratumoral concentrations of ethanol, thus potentially allowing researchers to achieve the requisite concentrations for maximal tumoricidal effects.

Detection of atherosclerosis via magnetic resonance imaging

Magnetic resonance imaging (MRI) of atherosclerotic lipids using a stimulated-echo diffusion- weighted (STED) sequence is demonstrated. The STED sequence exploits the large difference in diffusion between lipid (primarily cholesteryl ester) and water. The optimization of the STED sequence is discussed. The results of lipid imaging are corroborated with nuclear magnetic resonance (NMR) spectroscopy. This technique is non-invasive, and therefore, it is potentially useful in following the progression of the disease in animal models and in humans.

Fluorescence spectroscopy of normal and atheromatous human aorta: optimum illumination wavelength

The purpose of this investigation was to determine which illumination wavelength produces the largest differences between the fluorescence emission spectra of normal and atheromatous vascular tissue. The fluorescence spectra for 12 excitation wavelengths ranging between 270 nm and 470 nm were examined and compared. The Hotelling trace, a figure of merit describing class separability, was used to compare the excitation wavelengths. Preliminary results indicate that illumination in the range from 314 nm to 334 nm consistently performed well. Wavelengths in the 364 nm to 436 nm range also showed promising performance for a limited data set. These results were found to be relatively independent of the catheter angel and distance to the tissue.

Optimum illumination wavelength for fluorescence spectroscopy of atheromatous plaque

Seven illumination wavelengths from 270 to 364 nm were investigated for their ability to produce differences in the fluorescence spectra between normal aorta and atheromatous plaque. Differences in the spectra were evaluated using the Hotelling trace and ROC methods. The results indicate that large spectral differences and, therefore, good classification can be obtained with illumination in the range from about 304 to 334 nm and that the performance drops off rapidly on either end of the illumination range.