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T L Richards

Publications and source records attributed to T L Richards.

At least 37 records · Page 2Linked to original sources
PubMed1995

Incorporation of a phosphonium analogue of choline into the rat brain as measured by magnetic resonance spectroscopy.

A clear understanding of choline metabolism is important in our goal to modify demyelination and remyelination in multiple sclerosis. To develop a technique capable of measuring metabolic changes in the brain, we have studied the incorporation of a phosphonium analogue of choline (P-choline) in tissue extracts of rats. After feeding adult rats a choline-deficient diet supplemented with P-choline, the analogue was not detectable by in vivo volume-localized 1H spectroscopy. However, in vitro 31P measurements of brain extracts revealed an 11% incorporation of P-choline into phosphatidylcholine. We report that P-choline incorporates preferentially into the lipid pool over the lipid precursor pool and we provide evidence that the choline peak resolved by in vivo 1H spectroscopy is only composed of small molecular weight choline-containing compounds.

Animals↗
PubMed1995

Experimental allergic encephalomyelitis in non-human primates: MRI and MRS may predict the type of brain damage.

Volume-localized proton spectroscopy and T2-weighted MRI were performed on 23 monkeys with experimental allergic encephalomyelitis (EAE). The purpose of this study was to determine the relationships between temporal changes in lesion activity (measured on T2-weighted MRI), MRS [N-acetyl aspartate (NAA), creatine (CR), choline (CHO)], and the histologic definition of disease determined post-mortem. Animals were scanned in the same areas of the brain once a week before and after sensitization to myelin basic protein (BP). Histologic lesion types were predicted by a combination of preceding MRI and MRS measurements. Acutely fatal EAE lesions were large and monophasic as visualized by MRI, and increased CHO (p < 0.02, n = 16) and CHO/CR ratio (p < 0.001, n = 16) were detected by MRS at disease onset. Chronic EAE lesions were preceded by multiple inflammatory attacks as visualized by MRI and consistently low levels of NAA (p < 0.02, n = 13) and NAA/CR (p < 0.01, n = 13) which occurred after the initial attack. MRI negative brain regions (from animals that were sensitized to BP) were associated with low CHO/CR (p < 0.1, n = 5). The temporal correlation of MRI lesion activity and absolute MRS proton metabolites shows promise for predicting the subsequent duration and histologic type of lesions in EAE in non-human primates.

Animals↗
PubMed1995

Proton magnetic resonance spectroscopy investigation of hyperventilation in subjects with panic disorder and comparison subjects.

OBJECTIVE: The purpose of this study was to investigate differential effects of hyperventilation on brain lactate in patients with panic disorder and comparison subjects as a possible mechanism for explaining previous observations of an excess rise in brain lactate among panic disorder subjects during lactate infusion. METHOD: Seven treatment-responsive patients with panic disorder and seven healthy comparison subjects were studied with proton magnetic resonance spectroscopy to measure brain lactate during controlled, voluntary hyperventilation over a period of 20 minutes. Hyperventilation was regulated with the use of capnometry to maintain end-tidal PCO2 at approximately 20 mm Hg during the period of hyperventilation. Blood lactate was measured prior to and at the end of hyperventilation. RESULTS: At baseline the two groups had similar brain lactate levels. Panic disorder subjects exhibited significantly greater rises in brain lactate than comparison subjects in response to the same level of hyperventilation. Blood lactate levels before and after 20 minutes of hyperventilation were not significantly different between groups. CONCLUSIONS: Controlled hyperventilation increases brain lactate and does so disproportionately in subjects with panic disorder. This increase in brain lactate may result from decreased cerebral blood flow due to hypocapnia, and individuals with panic disorder may have greater sensitivity to this regulatory mechanism.

Adult↗
PubMed1995

Experimental allergic encephalomyelitis in non-human primates: diffusion imaging of acute and chronic brain lesions.

Diffusion imaging and T2-weighted magnetic resonance imaging were performed on 16 monkeys with experimental allergic encephalomyelitis (EAE), a model of the human demyelinating disease MS. The purpose of this study was to determine whether local changes in diffusion image intensity could be correlated with the formation of acute and chronic demyelinating lesions. Diffusion image analysis was restricted to the internal capsule of the brain because of its anatomic orientation of fiber pathways. Acute inflammatory EAE lesions were large and monophasic, as visualized by T2-weighted MRI, and were accompanied by a decrease in the diffusion MR image signal with the diffusion-sensitizing gradient in all three orthogonal directions (n = 27 brain regions, P < 0.005). Chronic demyelinating lesions were preceded by multiple inflammatory attacks, as visualized by MRI, and by a decrease in diffusion MR image signal with the diffusion-sensitizing gradient in the two orthogonal directions perpendicular to the fibers of the internal capsule (n = 18 brain regions, P < 0.005). However, for the chronic group, there was no significant change in the diffusion MR image signal with diffusion-sensitizing gradient parallel to the fibers of the internal capsule at the terminal scan, suggesting little change in the water diffusion within the nerve fibers. These results suggest that diffusion imaging holds promise for measuring subtle changes in water diffusion due to different types of brain damage.

Acute Disease↗
PubMed1994

Preliminary application of magnetic resonance spectroscopy to investigate lactate-induced panic.

OBJECTIVE: To characterize changes associated with lactate-induced panic, proton magnetic resonance spectroscopy (MRS) was used to measure brain lactate during intravenous infusion of 0.5-M sodium lactate in panic disorder patients and comparison subjects. METHOD: Eight panic disorder subjects, five medicated and three unmedicated, and eight healthy comparison subjects were studied at baseline, during lactate infusion (5 meq/kg over 20 minutes), and after infusion. Localized proton MRS was used to acquire averaged spectra every 5 minutes from a 27-ml sampling volume in the insular cortex and adjacent regions. Brain lactate levels, quantitatively estimated in relationship to N-acetyl aspartate, were compared to blood lactate levels. RESULTS: The procedure was generally well tolerated; one panic subject requested early termination before lactate infusion. Significant rises in brain lactate levels occurred for all subjects during infusion. The panic patients who responded to lactate (N = 3) had significantly higher brain lactate levels before, during, and after infusion than did the comparison subjects (N = 8) and medicated patients who were lactate nonresponders (N = 4). After infusion the panic patients with lactate-induced panic exhibited a striking dissociation between decreasing blood lactate and further increases in brain lactate levels. CONCLUSIONS: These preliminary observations indicate that brain lactate increases during a standard lactate infusion. Lactate-induced panic is associated with greater increases than in comparison subjects and with prolonged elevations in brain lactate that are decoupled from falling blood lactate levels after completion of lactate infusion. Further investigation is necessary to clarify the mechanism(s) responsible for these findings and establish whether a causal relationship to the occurrence of lactate-induced panic exists.

Adult↗
PubMed1993

Diffusion imaging of experimental allergic encephalomyelitis.

Diffusion-weighted magnetic resonance imaging (MRI) was compared with T2-weighted MRI in longitudinal studies of experimental allergic encephalomyelitis (EAE), an animal model of multiple sclerosis, in five monkeys (Macaca fascicularis). In a region of the brain that had highly directional myelinated fibers (internal capsule) sequential changes were identified on diffusion-weighted images on and before the day these changes were detected on conventional T2-weighted images. Changes were also identified on diffusion-weighted images in brain areas that did not develop T2-weighted abnormalities. This result suggests that diffusion-weighted image intensities are sensitive to pathologic conditions of the brain that can not be seen on T2-weighted images.

Animals↗
PubMed1992

MRS detection of whole brain lactate rise during 1 M sodium lactate infusion in rats.

Proton magnetic resonance spectroscopy (1H MRS) performed in vivo on nine Sprague Dawley rats detected a threefold increase in whole brain lactate during intravenous 1 mol/L sodium lactate infusion. Significant increases in whole brain lactate were detected within 5 min after starting lactate infusion, progressively rose to a maximum level estimated at 3.2 +/- 1.5 mmol/L (all values +/- SD) immediately postinfusion, then decreased towards baseline levels during the next hr. Venous lactate concentration, increasing from 2.3 +/- 2.4 mmol/L to 43.0 +/- 8.0 mmol/L during the infusion, exhibited a steeper rise and then decreased more rapidly in comparison to changes in whole brain lactate. These data suggest MRS can be used in vivo to study acute changes in brain lactate associated with increasing blood lactate concentrations.

Animals↗
PubMed1992

In vivo phosphorus NMR spectroscopy of skin using a crossover surface coil.

A modified crossover surface coil with minimal B1 field penetration was used for collection of skin phosphorus NMR spectra. Projection imaging experiments show that the coil-sensitive volume is uniform at the phosphorus frequency, but strikingly nonuniform at the proton frequency. Experiments with an in vitro phosphorus phantom, designed to simulate skin and underlying tissue, demonstrated that 45.1% (+/- 1.2%) of total signal was derived from Sprague-Dawley rat skin and 19.3% (+/- 1.4%) of total signal was derived from Fischer-344 rat skin. 31P MR spectra of rat skin in vivo permitted resolution of four phosphorus compounds: nucleoside triphosphates, phosphocreatine (PCr), inorganic phosphate (Pi), and phosphomonoester. Spectra collected after skin flap surgery in Fischer-344 rats showed a 50.1% (+/- 7.6%) reduction in the ratio of PCr/Pi within 30 min of surgery, compared to presurgical PCr/Pi levels (P less than 0.01). Skin phosphorus spectra are potentially useful for assessment of skin flap and skin graft viability.

Animals↗
PubMed1992

Localized magnetic resonance spectroscopy measurement of brain lactate during intravenous lactate infusion in healthy volunteers.

Proton magnetic resonance spectroscopy (1H MRS) localized to the left temporal-parietal region in 8 healthy volunteers detected a 2.1-fold +/- 0.7-fold increase (all values +/-SD) in brain lactate during intravenous infusion of 0.5 molar (M) sodium lactate (5 meq/kg over 20 minutes). Significant increases in brain lactate occurred within 5-10 minutes after starting lactate infusion, progressively rose during the infusion, then decreased towards baseline levels during 30 minutes post-infusion. Venous lactate concentration increased from 0.8 +/- 0.2 mM to 10.9 +/- 4.1 mM or 13.6-fold during the infusion. Flow phantom findings in vitro suggest attenuation of 1H MRS blood lactate signal from arteries and veins as a result of flow velocity effects. Correlations between paired blood and brain lactate measurements at each sampling time indicate a non-linear relationship between compartments during lactate infusion.

Adult↗
PubMed1991

1H NMR spectroscopic imaging of the monkey brain using binomial water suppression in a stimulated-echo sequence.

A new proton, two-dimensional pulse sequence for 1H NMR spectroscopic imaging (chemical shift imaging) was tested in phantoms and in the monkey brain. The pulse sequence consisted of one binomial chemically selective pulse and two spatially selective pulses in the stimulated-echo sequence. The point-spread function (which is influenced by k-space filtering and the number of phase-encoded steps) of a 1 mm source phantom was measured using a 16 x 16 spatial matrix and was found to have a FWHM of 10 mm (100 mm field of view) with very little rippling outside the main lobe. The binomial excitation profile was measured in order to correct the NMR intensity for the variable flip angles. Spectroscopic images were measured in the monkey brain with a 15 mm slice thickness and a 16 x 16 spatial matrix. Proton spectra derived from the brain contained sharp resonances of choline, creatine and N-acetyl aspartate with minimal lipid contamination. Proton spectra derived from the subcutaneous fat and adipose tissue behind the eyes contained large lipid resonances.

Animals↗
PubMed1991

Proton MR spectroscopy in multiple sclerosis: value in establishing diagnosis, monitoring progression, and evaluating therapy.

MR imaging is currently the technique of choice for evaluating brain lesions in patients with multiple sclerosis (MS). In addition to MR imaging, proton MR spectroscopy has shown potential in diagnosing MS and monitoring the progression of treatment. Spatially localized proton spectroscopy has been used to evaluate changes in choline, creatine, N-acetyl aspartate (NAA), lipids, and lactate in MS patients and in animal models of MS. The main spectroscopic findings are a decrease in the NAA:creatine ratio and an increase in the choline:creatine ratio in brain regions that include plaques defined by MR imaging. Proton MR spectroscopy along with MR imaging may be helpful in distinguishing those early lesions that might respond to therapy from late irreversible lesions. Preliminary evidence suggests that although the proton spectra acquired from patients with various brain diseases are similar (high choline, low NAA), there are differences in other resonances (lipids, lactate, glutamate, inositol) that could potentially help in diagnosing MS. Changes in proton metabolites potentially can be used to differentiate between the different stages of the MS lesion (hyperacute and edematous lesions, demyelinated lesions, and subacute to chronic plaques). It is hypothesized that successful treatment of demyelination and neuronal damage will be accompanied by changes in the proton spectrum (high choline:creatine ratio will lower to normal values and low NAA:creatine values will rise to normal values).

Animals↗
PubMed1989

Measurement of tissue oxidation-reduction state with carbon-13 nuclear magnetic resonance spectroscopy.

The oxidation state of tissues influences their response to cancer therapy. We have devised a novel approach to the measurement of thiol redox which is based on the relative nuclear magnetic resonance signal intensity from carbon-13 adjacent to sulfur in metabolites of the redox-sensitive phosphorothioate drug, S-2-(3-methylaminopropylamino)ethylphosphorothioic acid (WR3689). Incubation of WR3689 metabolites under oxidizing conditions results in quantifiable changes in the 13C nuclear magnetic resonance spectrum stoichiometrically related to the degree of oxidation in mouse liver homogenate in vitro. Drug oxidation is competitive with the oxidation of tissue-derived thiol groups under these conditions. Noninvasive measurement of redox state may assist in designing more effective strategies for altering normal and malignant tissue response to cancer therapy.

Amifostine↗
PubMed1989

Magnetic resonance imaging and peripheral blood abnormalities in experimental allergic encephalomyelitis.

Experimental allergic encephalomyelitis (EAE) was induced in twelve cynomologous macaques (Macaca fascicularis) by sensitization to autologous myelin basic protein (BP) in complete Freund's adjuvant (CFA). The white blood cell (WBC) count, absolute number of lymphocytes and absolute numbers of CD4+ and CD8+ T-cell subsets were measured weekly. Using magnetic resonance imaging (MRI), the animals were monitored twice weekly for the development of central nervous system (CNS) lesions. Conventional spin-warp imaging was performed using a General Electric CSI-II NMR imager/spectrometer (2 Tesla magnet). CNS lesions were detected by MRI in all of the animals sensitized to myelin BP. Longitudinal analysis of their peripheral blood leukocytes revealed a progressive leukocytosis and lymphopenia, which always preceded the onset of clinical signs and almost always also preceded the formation of detectable CNS lesions. These results suggest that frequent analysis of T-cell subsets may provide a more accurate means of predicting episodes of disease activity than clinical or MRI evaluation.

Animals↗
PubMed1989

Separation of lipids from lactate in experimental allergic encephalomyelitis by zero quantum NMR techniques.

Using localized proton spectroscopy, the author and associates previously have observed an increase in the resonance at 1.2 +/- 0.2 ppm in the brain of monkeys with experimental allergic encephalomyelitis (EAE). In proton nuclear magnetic resonance (NMR) spectroscopy, the lactate methyl protons resonate at dose to the same chemical shift frequency as the lipid methylene protons (1.2 +/- 0.2 ppm). Noninvasive zero quantum NMR techniques were used to separate lipids from lactate in the brain during the course of EAE development. Out of 53 zero quantum NMR measurements (from three animals), 16 measurements were made at a time when a resonance at 1.2 ppm appeared (after the animals developed EAE). In all these cases, lactate was not detectable. The fact that the resonance (identified as lipids with zero quantum techniques) correlated with histochemical Oil red O staining suggests that these mobile NMR signals are associated with demyelination.

Animals↗
PubMed1989

MR appearance of gallstones in vitro at 1.5 T: correlation with chemical composition.

Gallstones from 63 patients were evaluated by in vitro 1.5-T MR imaging, with T1- and T2-weighted images, and in 14 cases, a fat-suppression sequence (short-T1 inversion recovery imaging). Subsequent chemical analysis was performed on 43 gallstones. In vitro proton MR spectroscopy was performed on 14 stones. On T1-weighted MR images, foci of increased signal were seen in 46 of 63 stones (faint in 17, moderate in nine, and bright in 20). T2-weighted images showed areas of increased signal in 18 of 63 stones (faint in 15, moderate in three). T1-weighted MR imaging patterns were homogeneously dark (17), homogeneously bright (two), homogeneously faint (three), rimmed (dark rim and bright center, 32), and laminated (nine). Short-T1 inversion recovery imaging suppressed the foci of increased signal in 13 of 14 cases. Despite imaging characteristics suggestive of high lipid content, spectroscopy revealed only a single peak corresponding to a large water-proton signal. The T1 relaxation times of the water were shortened, ranging from 0.006 to 0.92 sec, explaining the increased signal seen on MR images of the gallstones. MR imaging characteristics (signal intensity, relative signal area, or imaging patterns) did not correlate with chemical composition. We hypothesize that different structural relationships must exist within gallstones of similar chemical content that alter the water bonding and hence the MR imaging characteristics.

Cholelithiasis↗
PubMed1987

Measurement of lactate accumulation by in vivo proton NMR spectroscopy during global cerebral ischemia in rats.

In vivo 1H NMR spectral editing techniques were used to monitor cerebral lactate production during remotely controlled temporary forebrain ischemia in rats. The lactate/N-acetylaspartate (NAA) ratio correlated with survival after ischemia and subsequent reperfusion. The lactate/NAA ratio that predicted death after ischemia in rats was estimated to be approximately 1.3.

Animals↗
PubMed1987

Lactate accumulation in ischemic- and anoxic-isolated rat hearts assessed by H-1 spectroscopy.

Proton magnetic resonance (MR) spectroscopy with homonuclear editing was used to assess lactate accumulation in ischemic and anoxic hearts perfused according to the Langendorff method. An increase in the lactate signal was observed after 5 minutes of ischemia and after 10 to 20 minutes of anoxia. This study demonstrates that proton MR spectroscopy can be used to monitor the time course of MR-visible lactate levels in ischemic and anoxic isolated rat hearts.

Animals↗