Richard L. Ehman

Translational molecular self-diffusion in magnetic resonance imaging. II. Measurement of the self-diffusion coefficient.

By varying slice-selective gradients in successive data acquisitions, the first in vitro measurements of molecular self-diffusion coefficients were performed in a magnetic resonance imager at 0.35 Tesla. Reasonably accurate measurements were found by the MRI method in comparison with 2.3 T NMR spectrometer measurements on the same samples, and in comparison to reported literature values. Thus, in addition to T1, T2, mobile proton density, flow velocity, magnetic susceptibility, and chemical shift, molecular self-diffusion coefficients are now added to the list of biophysical parameters measurable by magnetic resonance imaging in the noninvasive characterization of biological systems.

Enhanced MRI of tumors utilizing a new nitroxyl spin label contrast agent

Nitroxyl spin labels have been shown to be effective in vivo contrast agents for magnetic resonance imaging (MRI) of the central nervous system, myocardium, and urinary tract. A new pyrrolidine nitroxyl contrast agent (PCA) with better resistance to in vivo metabolic inactivation than previously tested agents was studied for its potential to enhance subcutaneous neoplasms in an animal model. Twenty-two contrast enhancement trials were performed on a total of 15 animals 4-6 weeks after implantation with human renal adenocarcinoma. Spin echo imaging was performed using a .35 T animal imager before and after intravenous administration of PCA in doses ranging from 0.5 to 3mM/kg. The intensity of tumor tissue in the images increased an average of 35% in animals receiving a dose of 3 mM/kg. The average enhancement with smaller doses was proportionately less. Tumor intensity reached a maximum within 15 min of injection. The average intensity difference between tumor and adjacent skeletal muscle more than doubled following administration of 3 mM/kg of PCA. Well-perfused tumor tissue was more intensely enhanced than adjacent poorly perfused and necrotic tissue.

Relative intensity of abdominal organs in MR images.

Knowledge of the normal relative intensity of organs and tissues is a valuable aid to clinical interpretation of magnetic resonance images. In this study the in vivo spin echo image intensities of normal parenchymal organs and other structures in the upper abdomen were evaluated for eight parameter combinations. The examinations of 40 patients were used. Image intensity and calculated TI, T2, and spin density values were obtained for liver, spleen, pancreas, renal cortex, renal medulla, bone marrow, skeletal muscle, and fat. Repetition times (TR) of 500, 1,000, 1,500, and 2,000 ms and echo times of 28 and 56 ms were used. The T1 and T2 values and relative spin density were calculated using a new algorithm. Liver had the smallest relative standard deviation of T1 of all the tissues studied. For comparison purposes, relative image intensities were calculated by normalizing them to the intensity of liver in the same image. The resulting compiled data show the normal ranks and ranges for relative intensity for the tissues in each of eight types of spin echo images. Although images with short TR and echo time (TE) are known to display the greatest T1 contrast, the mean relative intensities of all tissues except muscle and fat in the TR = 500 and TE = 28 ms images were within 20% of liver. A much larger spread in the normal relative intensities was observed with longer TE and TR.

Translational molecular self-diffusion in magnetic resonance imaging. I. Effects on observed spin-spin relaxation

The reduced T2 (spin-spin) relaxation times (T2obs less than 200 ms) measured on pure fluids on our 0.35T magnetic resonance imagers stimulated an investigation into this phenomenon. The cause for the short T2obs of fluids was found to be translational molecular self-diffusion of hydrogen nuclei through the pulsed slice-selective magnetic gradient in the imagers. Similar reductions in biological tissue T2obs were also attributed to molecular self-diffusion.

Diradical nitroxyl spin label contrast agents for magnetic resonance imaging. A comparison of relaxation effectiveness.

The proton relaxation enhancement characteristics of seven potential MRI contrast agents containing two nitroxyl spin labels per molecule (diradicals) were compared with eight similar agents with only one spin label per molecule (monoradicals). Diradical nitroxyls were evaluated to test the hypothesis that multiple paramagnetic centers in one molecule will result in stronger proton relaxation enhancement characteristics, allowing effective contrast enhancement at lower molar concentrations and thus a reduced osmotic load and greater safety. The acute toxicity of these agents is believed to be largely related to osmotic load. Five of seven diradical nitroxyls tested had spin-lattice relaxivities that were substantially greater than all eight of the monoradicals tested. The spin-spin relaxation properties of these agents and other pertinent characteristics are favorable for contrast enhancement. The results indicate that diradical nitroxyl spin labels may be used advantageously for the design of safer, more effective MRI contrast agents.

Magnetic resonance imaging in the diagnosis of acute renal allograft rejection and its differentiation from acute tubular necrosis. Experimental study in the dog.

This study was designed to evaluate the potential utility of magnetic resonance imaging (MRI) for the diagnosis of acute renal allograft rejection and its differentiation from acute tubular necrosis (ATN). Eighteen canines were used. Five animals served as controls. ATN was induced in six animals by cross-clamping of the left renal artery for 90 minutes. In order to study acute renal allograft rejection, seven animals were subjected to exchange allograft transplantation of the left kidney. MRI was performed with a 0.35T superconductive magnet. A double spin-echo technique was used with varying TR and TE parameters. The spin echo images were analyzed for morphology, signal intensity, T1 and T2 relaxation times, and spin density. The most useful MRI criteria for the diagnosis of ATN and acute rejection were found to be the renal size, the intensity difference between cortex and medulla (corticomedullary contrast), and the T1 relaxation time of the cortex. Normal kidneys showed maximal corticomedullary contrast (19% +/-2) on images obtained with TR = 0.5 sec and TE = 28 msec. Cortical T1 relaxation time was 551 msec + /-73. In the ATN group, the kidneys were slightly swollen (P = ns) and the corticomedullary contrast (11% + /-3) was reduced by 42% (P less than .01). T1 of the cortex (689 + /-142) was increased by 25% (P less than .10). In acute rejection, significant renal enlargement was noted (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of chemical structure on nitroxyl spin label magnetic relaxation characteristics

Abstract An attempt was made to develop guidelines for the design of new contrast agents using nitroxyl spin labels (NSL). The structural parameters of ring size and of substituents were correlated with the stability towards reduction and the relaxation effectiveness using 5 piperidine and 5 pyrrolidine nitroxyls containing the same substituents. The susceptibility of NSL to reduction was assessed by EPR spectroscopy. The relaxation effectiveness of NSL on protons in buffer and plasma solution was measured on a NMR spectrometer. The ring size and substituents has a decisive effect on the stability of NSL, whereby the ring size effect was dominant. In the case of spin—lattice relaxivities (R 1 ) and spin-spin relaxivities (R 2 ), the ring size and the substitution effect were marginal in buffer solution, while in plasma these effects were more pronounced. A number of guidelines were proposed for the design of suitable NSL contrast agents for MRI.