Using a one-dimensional rapid imaging technique, we have found that injection of lanthanide chelates such as Gd(DTPA)2- leads to a significant decrease (50%) in rat brain signal intensity at 1.45 T using T2-weighted pulse sequences; however, no effect of comparable size is observed with T1-weighted pulse sequences. The transient effect and its kinetics were followed with a temporal resolution of between 1 and 8 s. Experiments with different lanthanide chelates show that the observed decrease in signal intensity correlates with the magnetic moment of each agent but not with their longitudinal relaxivity. Three-dimensional chemical-shift resolved experiments demonstrate significant line broadening in brain during infusion with Dy(DTPA)2-. Our results show that the cause of this effect is the difference in susceptibility between the capillaries, containing the contrast agent, and the surrounding tissue. As a result of these susceptibility differences, field gradients are produced in the tissue and diffusion of water through these gradients leads to a loss of spin phase coherence and thus a decrease in signal intensity. We propose this as a new type of contrast agent mechanism in NMR. The effect and its kinetics are likely to be related to important physiological parameters such as cerebral blood volume and cerebral blood flow, and do not depend on a breakdown of the blood-brain barrier as do conventional contrast agent techniques.

Previous measurements of the hydroxyl (OH-) ion content of the calcium phosphate crystals of bone mineral have indicated a substantial depletion or near-absence of OH-, despite its presumed status as a constituent of the hydroxyapatite lattice. Analytical methods for determining bone crystal OH- content have depended on procedures or assumptions that may have biased the results, such as chemical pretreatment to eliminate interference from the organic matrix. We demonstrate a two-dimensional solid-state nuclear magnetic resonance (NMR) spectroscopy technique that detects the proton spectrum of bone crystals while suppressing the interfering matrix signals, eliminating the need for specimen pretreatment other than cryogenic grinding. Results on fresh-frozen and ground whole bone of several mammalian species show that the bone crystal OH- is readily detectable; a rough estimate yields an OH- content of human cortical bone of about 20% of the amount expected in stoichiometric hydroxyapatite. This finding sheds light on the biochemical processes underlying normal and abnormal bone mineral metabolism.

We calculate the effects of subvoxel variations in magnetic susceptibility on MR image intensity for spin-echo (SE) and gradient-echo (GE) experiments for a range of microscopic physical parameters. The model used neglects the overlap of gradients from one magnetic inclusion to the next, and so is valid for low volume fractions and weak perturbations of the magnetic field. Transverse relaxation is predicted to deviate significantly from linear exponential decay in both SE and GE at a particle radius of 2.5 microns. Calculated changes in transverse relaxation rates for SE and GE increase linearly with volume fraction of high-susceptibility regions of 5 microns diameter, but increase with about the 3/2 power of volume fraction of regions with 15 micron spacing between centers. This sensitivity to the actual size and spacing of magnetized regions may allow them to be measured on the basis of contrast. without being resolved in images. GE and SE decay rates are approximately twice as sensitive to long cylinders of 5 microns diameter than to spheres of the same size, for diffusion constants of 2.5 micron 2/ms. Calculated changes in transverse decay rates increase with approximately the square of field and susceptibility variation for 5-microns spheres and a diffusion constant of 2.5 microns 2/ms. This exponent is smaller for cylindrical magnetized regions of the same size, and also depends on the diffusion constant. We discuss possible applications of our theoretical results to the analysis of the effects of high-susceptibility contrast agents in brain. Experimental data from the literature are compared with calculated signal changes according to the model. The monotonic dependence of decay rates on the volume of distribution of the contrast agent suggests that cerebral blood volume and flow could be measured using MR contrast.

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Proton NMR spectroscopy has proven useful in the detection of cancer in lymph node tissue. However, due to the high fat content of this type of tissue, 2D 1H COSY measurements (requiring acquisition times of 4-5 h or longer) are necessary to obtain the spectral information necessary for diagnosis. T2-filtered proton magic-angle spinning (MAS) NMR spectroscopy provides 1D spectra of lymph nodes in approximately 20 min with sufficient spectral resolution allowing for identification of changes in cellular chemistry due to the presence of malignant cells. MAS data from lymph nodes of five control and six rats with mammary adenocarcinoma (R13762) demonstrated increases in the signal intensity of resonances associated primarily with lactate (delta = 4.12 ppm) P < 0.0004, creatines/lysine (delta = 3.04 ppm) P < 0.0032, and glutamate/ glutamine (delta = 2.36 ppm) P < 0.0002 in metastatic compared with normal lymph nodes. The infiltration of lymph nodes by malignant cells is an important prognostic factor for many cancers. The rapid assessment of node tissue without the introduction of sampling errors (inherent in currently employed histological procedures) would allow postoperative therapy decisions to be made more efficiently.

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