Proton MR spectroscopy and neuropsychological testing in adrenoleukodystrophy.

PURPOSE: To determine early signs of disease in patients with childhood-onset cerebral adrenoleukodystrophy (COCALD) with the use of proton MR spectroscopy. METHODS: Eleven children with posterior COCALD involvement and three children with anterior COCALD involvement were studied with single-voxel proton MR spectroscopy and neuropsychological testing. Findings were compared with those in five healthy control subjects. RESULTS: Areas of abnormal T2 signal intensity in children with COCALD showed abnormal metabolite ratios relative to those of control subjects as follows: decreased N-acetylaspartate (NAA)/Creatine (Cr) and NAA/Choline (Ch) and increased Ch/Cr. Metabolite ratios from normal-appearing brain regions in the same patients also were abnormal, with reduced NAA/Cr and NAA/Ch and increased Ch/Cr values. The mean metabolite ratios in normal-appearing regions were between those in the abnormal regions and those found in the control subjects. Statistical comparison of these ratios with neuropsychological test scores, which are specific for anterior and posterior brain functions, showed a significant correlation with the abnormal metabolite ratios. Our results indicate that the normal-appearing brain regions in these patients are metabolically abnormal. CONCLUSION: Proton MR spectroscopy could be a useful noninvasive tool to evaluate extent of disease in patients with COCALD.

Proton MR spectroscopy of childhood adrenoleukodystrophy.

PURPOSE: To determine the potential of proton MR spectroscopy to monitor patients with childhood-onset cerebral adrenoleukodystrophy (COCALD). METHODS: Single-voxel MR spectroscopy was performed in 16 children with COCALD (24 examinations) who had had no treatment and in 7 children (13 examinations) who had had bone marrow transplantation. RESULTS: In the untreated children with clinically active COCALD, the metabolite ratios N-acetyl-aspartate (NAA)/creatine (Cr) and NAA/choline (Ch) were decreased while Ch/Cr was increased. This trend agrees well with those reported by other researchers, although different experimental sequences and parameters were used in our study. Comparison of these ratios with those from a control group yielded significant differences in the occipital region. In the children who were clinically stable after bone marrow transplantation, the mean levels of the three ratios were between those of the control subjects and the patients with untreated COCALD: the differences in these ratios approached significance. In patients who had been monitored periodically, MR spectroscopy metabolite ratios correlated well with the dementia rating score, reflecting clinical status. CONCLUSION: There is good correlation between MR spectroscopy metabolite ratios and a patient's clinical status. MR spectroscopy appears to be a useful, noninvasive tool to monitor patients with adrenoleukodystrophy, and it increases the overall sensitivity of MR techniques in clinical applications.

Quantitative magnetic resonance flow and diffusion imaging in porous media.

Quantitative flow and diffusion measurements have been made for water in model porous media, using magnetic resonance micro-imaging methods. The samples consisted of compacted glass beads of various sizes down to 1 mm diameter. Typical flow and diffusion images exhibited a spatial resolution of 117 microns x 117 microns and velocities in the range 1-2 mm/s. Comparison of volume flow rates calculated from the flow velocity maps with values measured directly yielded good agreement in all cases. There was also good agreement between the mean diffusion coefficient of water calculated from the diffusion maps and the bulk diffusion coefficient for pure water at the same temperature. In addition, the mean diffusion coefficient did not depend on the pore sizes in the bead diameter range of 1-3 mm. Our results also show that partial volume effects can be compensated by appropriate thresholding of the images prior to the final Fourier transformation in the flow-encoding dimension.

Magnetic resonance methods for measurement of disease progression in rheumatoid arthritis.

Magnetic resonance imaging methods are described for measurement of disease activity in knee in rheumatoid arthritis patients. Measurements of cartilage thickness, joint effusion volume, and pannus volume have been made. The latter measurement relies on synthetic fractional enhancement images of the response to gadopentetate dimeglumine.

Quantitative P-31 MR spectroscopy of the liver in alcoholic cirrhosis.

To determine the cause of reduced urea synthesis in cirrhosis, absolute concentrations of phosphorus metabolites in the human liver have been measured in vivo with magnetic resonance (MR) spectroscopy. One-dimensional chemical shift imaging was used to obtain phosphorus-31 spectra from five healthy volunteers and five patients with alcoholic cirrhosis. A reference standard included in all studies enabled the calculation of absolute concentrations. In contrast to hepatic metabolite ratios, absolute concentrations reveal that in the cirrhotic patients, concentrations of adenosine triphosphate (ATP) were significantly reduced and concentrations of phosphomonoesters slightly reduced. Intracellular pH was unchanged. Histologic evidence suggests that the amount of ATP per cell was unchanged and could not account for the reduced urea production. Instead, urea synthesis depends on the functional liver cell mass, which was reduced by 31% in alcoholic cirrhosis. Quantitative in vivo P-31 MR spectroscopy of liver has potential clinical applications and can supplement the more generally used P-31 metabolite ratios.

Demonstration of endothelial adhesion of sickle cells in vivo: a distinct role for deformable sickle cell discocytes.

Different morphologic and density classes of sickle cells (SS) may play distinct roles in the generation of vasoocclusion, explaining the complexity of this phenomena. The densest SS red blood cells (RBCs) (SS4) can induce vasoocculsion in ex vivo microcirculatory preparations as well as in an intact animal model. Previous studies of the interaction of SS deformable discocytes with endothelial monolayers or the rat ex vivo mesocecum preparation have shown adhesion that is desmopressin (dDAVP)-stimulated, von Willebrand factor (vWF)-mediated, and limited to the small venules. However, in vivo adhesion of SS RBCs to the endothelium has neither been demonstrated nor characterized; and, in particular, the relation of adhesion to vasoocclusion is unknown. Using an intact animal model that involves injecting saline-washed, density-defined SS RBCs into the femoral artery of a rat, we find that: (1) Quantitative studies of RBCs retained in the rat thigh using 99mTc-labeled RBCs and gamma camera imaging showed that dDAVP induces a threefold increase in retention of normal (AA) cells and deformable SS discocytes (SS2). (2) electron microscopy and Microfil injection show that the retention of SS2 cells is due to adhesion to the vascular endothelium with no evidence of obstruction. (3) H-1 magnetic resonance imaging showed that retention of SS4 cells induced a dose-dependent increase in tissue edema (presumable secondary to tissue hypoxia), while retention of AA or SS2 cells produced no change. We conclude that endothelial adhesion of deformable SS discocytes can be demonstrated in an in vivo animal model, that this adhesion is enhanced by dDAVP (presumably related to, but not necessarily limited to the release of vWF), and that this phenomenon per se does not lead to vasoocclusion. Nevertheless, adhesion of deformable SS discocytes may have consequences. We hypothesize that adhesion of SS discocytes could narrow the lumen of postcapillary venules and facilitate secondary trapping of SS4 cells and lead to subsequent vasoocclusion.

Endorectal surface coil MR imaging of prostatic carcinoma with the inversion-recovery sequence.

The value of inversion-recovery (IR) sequences in the diagnosis and staging of prostatic carcinoma with magnetic resonance (MR) imaging was studied. Twenty-six patients with carcinoma of the prostate were imaged at 1.5 T with an endorectal surface coil and with a variety of IR sequences and a set of spin-echo (SE) sequences for comparison. Ex vivo prostate specimens were imaged again at the same field strength. The two images were correlated with histologic sections. Cancer was identified with MR imaging in 96% of patients. Of the tumors more than 4 mm in diameter, 87% were identified on T2-weighted SE images, whereas only 26% were identified on IR images. However, IR images may be more useful in local staging of carcinoma. Gross capsular infiltration was present in only two patients; however, it was detectable (and excluded in five other patients) by means of IR images. It was not detectable on SE images. The high quality of images obtained with the endorectal coil was confirmed. The authors conclude that addition of the IR sequence to MR imaging with the endorectal coil may improve the usefulness of this examination.

In vivo quantitation of water content in muscle tissues by NMR imaging.

The water contents of phantoms and muscle tissues were determined directly from NMR imaging experiments. The method involves the calculation of corrected proton densities using relaxation time determinations and suitable calibration phantoms. Comparison with the values obtained from the oven-dry method yields good agreement in normal rat skeletal tissue and in rats injected with red blood cells from sickle cell patients.

Modeling sickle cell vasoocclusion in the rat leg: quantification of trapped sickle cells and correlation with 31P metabolic and 1H magnetic resonance imaging changes.

We have developed an animal model to elucidate the acute effects of perfusion abnormalities on muscle metabolism induced by different density-defined classes of erythrocytes isolated from sickle cell anemia patients. Technetium-99m (99mTc)-labeled, saline-washed normal (AA), homozygous sickle (SS), or high-density SS (SS4) erythrocytes were injected into the femoral artery of the rat and quantitative 99mTc imaging, 31P magnetic resonance spectroscopy by surface coil at 2 teslas, and 1H magnetic resonance imaging at 0.15 tesla were performed. Between 5 and 25 microliters of SS4 cells was trapped in the microcirculation of the thigh (or 1-6 x 10(7) cells per cubic centimeter of tissue). In contrast, fewer SS discocytes (SS2) or AA cells were trapped (an equivalent packed cell volume of less than 6.7 microliters and 0.3 microliters, respectively). After injection of SS4 cells an initial increase in inorganic phosphate was observed in the region of the thigh served by the femoral artery, intracellular pH decreased, and subsequently the proton relaxation time T1 reached a broad maximum at 18-28 hr. When T1 obtained at this time was plotted against the volume of cells trapped, an increase of T1 over the control value of 411 +/- 48 msec was found that was proportional to the number of cells trapped. We conclude that the densest SS cells are most effective at producing vasoocclusion. The extent of the change detected by 1H magnetic resonance imaging is dependent on the amount of cells trapped in the microcirculation and the magnitude of the initial increase of inorganic phosphate.