Biomedical subjects

Rachel Katz-Brull

Publications and source records attributed to Rachel Katz-Brull.

9 recordsLinked to original sources

PubMed2006

Limits on activation-induced temperature and metabolic changes in the human primary visual cortex.

Changes in cerebral blood flow (CBF) and metabolism are now widely used to map and quantify neural activity, although the underlying mechanism for these changes is still incompletely understood. Magnetic resonance spectroscopy (MRS) at 3T, synchronized with a 32-s block design visual stimulation paradigm, was employed to investigate activation-induced changes in temperature and metabolism in the human primary visual cortex. A marginally significant increase in the local temperature of the visual cortex was found (0.1 degrees C, P = 0.09), excluding the possibility of a temperature decrease (95% confidence interval (CI) = 0.0-0.2 degrees C), which was previously suggested. A comparison with models of thermal equilibrium in the presence of blood flow suggests that an increase in heat production during activation, greater than or at least equal to that produced by the complete oxidative metabolism of the elevated glucose (Glc) utilization accompanying activation, would be required to offset the cooling effects of the increased blood flow. The total pools of glutamate (Glu), glutamine (Gln), myo-Inositol (mI), N-acetylaspartate (NAA), choline (Cho), and lactate (Lac) were not significantly affected by activation. Limits on Lac concentration changes were too weak to constrain theories of the metabolic use of elevated Glc consumption during stimulation, and emphasize the challenges of measuring even large Lac changes accompanying stimulation.

Adult↗

PubMed2005

Direct detection of brain acetylcholine synthesis by magnetic resonance spectroscopy.

The cholinergic system is an important modulatory neurotransmitter system in the brain. Changes in acetylcholine concentration have been previously determined directly in animal models and human brain biopsy specimens, and indirectly, by the effects of drugs, in living humans. Here, we developed a method for direct determination of acetylcholine synthesis in living brain tissue. The method is based on administration of choline, enriched with carbon-13 (stable isotope) in the two methylene positions, and detection of labeled acetylcholine and all other metabolic fates of choline, by carbon-13 magnetic resonance spectroscopy. We tested this method in rat brain slices and found it to be specific for acetylcholine synthesis in both the cortex and hippocampus. This method is potentially useful as a research tool for exploring the cholinergic system role in cognitive processes and memory storage as well as in diseases in which the malfunction of the cholinergic system has been implicated.

Acetylcholine↗

PubMed2004

Decreases in free cholesterol and fatty acid unsaturation in renal cell carcinoma demonstrated by breath-hold magnetic resonance spectroscopy.

Increased utilization of cross-sectional imaging has resulted in increased detection of incidental renal tumors. The noninvasive characterization of renal tissue has important implications for the diagnosis of renal malignancies and treatment monitoring. Recently, multiple breath-hold averaged proton magnetic resonance spectroscopy ((1)H-MRS) performed at high field has enabled the use of this noninvasive metabolic profiling technique for the investigation of the abdomen. Multiple breath-hold averaged (1)H-MRS at high field (3T) was obtained in the kidneys of 10 healthy volunteers and in renal cell carcinoma tumors of 14 patients. The spectra of normal kidneys showed four main groups of resonances: 1) at 5.4-5.6 ppm, attributed to C6 of cholesterol and the unsaturated parts of the olefinic region of fatty acids; 2) at 4.7 ppm, attributed to the residual water signal; 3) at 3.2 ppm, attributed to trimethylamine moiety of choline metabolites; and 4) at 1.3 and 0.9 ppm, attributed to the methylenes and terminal methyls of lipids. The ratio of the signal at 5.4 ppm to that of 1.3 ppm was 19-fold lower in renal cell carcinomas than in healthy kidneys, tied P = 0.0003 Mann-Whitney U-test, suggesting a decrease in both free cholesterol and the degree of unsaturation of fatty acids in the malignant tissue. This metabolic shift is in agreement with previous ex vivo studies of human renal cell carcinoma. The ability to detect renal metabolic shifts noninvasively may improve the specificity of preoperative renal tissue characterization and may provide a new modality for treatment monitoring.

Adult↗

PubMed2004

Elevation of myoinositol is associated with disease containment in progressive multifocal leukoencephalopathy.

MRI, 1H-MR spectroscopy, immunologic, and virologic studies were performed in search of prognostic factors of disease evolution in patients with progressive multifocal leukoencephalopathy (PML). Acute lesions of PML survivors showed twofold higher standard score of the ratio of myoinositol (a glial marker) to creatine compared with lesions in patients whose disease progressed. Concomitantly, JC virus-specific cytotoxic T lymphocytes were only detected in the blood of PML survivors. These results suggest that inflammation limits disease progression.

Adult↗

PubMed2004

Frame-by-frame PRESS 1H-MRS of the brain at 3 T: the effects of physiological motion.

1H-MRS at high field has been increasingly utilized to study brain metabolism in healthy and pathological states. The aim of this work was to determine the effects of physiological motion on the results of this exam in the presence of the increased susceptibility differences at high field. Single voxel spectra of various regions in the human brain were acquired using frame-by-frame PRESS 1H-MRS at a 0.5 Hz sampling rate. The frame-by-frame variations of the FID phase and the frequency and fractional amplitude variations of the residual water-signal were analyzed. In the human brain the standard deviations of these variations were 3.9 +/- 0.5 degrees, 0.83 +/- 0.32 Hz, and 0.028 +/- 0.013 of the mean amplitude (n=15). In a motionless phantom, smaller phase and frequency variations were detected in water-suppressed acquisitions. However, the end effects of physiological motion on PRESS 1H-MRS of the brain at 3 T were negligible.

Algorithms↗

PubMed2003

Breathhold abdominal and thoracic proton MR spectroscopy at 3T.

The clinical utility of proton MR spectroscopy ((1)H-MRS) has been well demonstrated in the brain, prostate, and breast. The aims of this work were to investigate 1) the feasibility of abdominal and thoracic (1)H-MRS at 3T, 2) the benefits of breathholding to MRS in these regions, and 3) the utility of multiple breathhold averaging for MRS. Breathholding either eliminated or markedly reduced phase and frequency shifts and outer voxel contamination that were associated with the motion of the abdomen and the thorax during breathing. Breathholding was found to be essential to spectroscopic investigation of the thorax. Spectra of renal cell carcinoma metastases in the abdomen and thorax were obtained utilizing multiple breathhold averaging. These spectra exhibited a resonance at 3.2 ppm attributed to the trimethylamine moiety of choline metabolites. The results of this study suggest a practical strategy for implementation of (1)H-MRS in the body.

Abdomen↗

PubMed2002

Choline in the aging brain.

Proton magnetic resonance spectroscopy has been increasingly utilized in brain research to monitor non-invasively metabolites such as N-acetyl aspartate (NAA), creatine (Cr) and choline (Cho). We present here studies of the effect of aging on the ratios of these metabolites measured in the rat brain in vivo and on choline transport and lipid synthesis in rat brain slices, in vitro. The in vivo studies indicated that the ratios of Cho/NAA and Cho/Cr increased in the aged hippocampus, whereas the ratio of Cr/NAA was similar in the aged and adult hippocampus. These three ratios remained similar in the cortex of adult and aged rats. The in vitro studies revealed that in the aged cortex and the aged hippocampus the activity of the low-affinity choline uptake increased, possibly compensating for a decrease in the high-affinity uptake activity and the rate of choline diffusion. The incorporation of choline into phospholipids exhibited high and low affinity kinetics which were not modified by aging.

Aging↗

PubMed2002

Clinical utility of proton magnetic resonance spectroscopy in characterizing breast lesions.

Proton magnetic resonance spectroscopy ((1)H MRS) of the breast has been proposed as an adjunct to the magnetic resonance imaging (MRI) examination to improve the specificity of distinguishing malignant breast tumors from benign breast tumors. In this review, we carry out a pooled analysis of the clinical breast (1)H MRS studies undertaken to date to determine the factors that influence the diagnostic performance of this method. In total, five studies of breast (1)H MRS from four independent centers around the world have been published to date. Altogether, 153 tumors were examined, 100 of which were confirmed histologically to be malignant and 53 of which were benign. The lesions presenting a detectable composite choline signal in their corresponding (1)H MR spectra were diagnosed as malignant, whereas the lesions with no choline signal were diagnosed as benign. The sensitivity and specificity of breast (1)H MRS for detecting breast cancer were 83% (95% confidence interval [CI] = 73% to 89%) and 85% (95% CI = 71% to 93%), respectively, and both values could be as high as 92% after technical exclusions. In a subgroup of 20 young women, the sensitivity and the specificity of the method approached 100%. The factors limiting the sensitivity of the examination were mainly technical. The use of the composite choline signal as a marker for malignancy in breast (1)H MRS is a robust method with highly reliable interpretation, because it is based on the appearance of a single peak. The method is likely to provide even better results with technologic advances in breast MRS that lead to the improved detection of the composite choline signal.

Age Factors↗

PubMed2002

Metabolic markers of breast cancer: enhanced choline metabolism and reduced choline-ether-phospholipid synthesis.

Specific genetic alterations during malignant transformation may induce the synthesis and breakdown of choline phospholipids, mediating transduction of mitogenic signals. The high level of water-soluble choline metabolites in cancerous breast tumors, relative to benign lesions and normal breast tissue, has been used as a diagnostic marker of malignancy. To unravel the biochemical pathways underlying this phenomenon, we used tracer kinetics and 13C and 31P magnetic resonance spectroscopy to compare choline transport, routing, and metabolism to phospholipids in primary cultures of human mammary epithelial cells and in MCF7 human breast cancer cells. The rate of choline transport under physiological choline concentrations was 2-fold higher in the cancer cells. The phosphorylation of choline to phosphocholine and oxidation of choline to betaine yielded 10-fold higher levels of these metabolites in the cancer cells. However, additional incorporation of choline to phosphatidylcholine was similar in both cell types. Thus, enhanced choline transport and augmented synthesis of phosphocholine and betaine are dominant pathways responsible for the elevated presence of choline metabolites in cancerous breast tumors. Uniquely, reduced levels and synthesis of a choline-ether-phospholipid may also serve as a metabolic marker of breast cancer.

Betaine↗