Biomedical subjects

J W Pan

Publications and source records attributed to J W Pan.

At least 37 records · Page 2Linked to original sources

PubMed1999

Measurement of the tricarboxylic acid cycle rate in human grey and white matter in vivo by 1H-[13C] magnetic resonance spectroscopy at 4.1T.

13C isotopic labeling data were obtained by 1H-observed/13C-edited magnetic resonance spectroscopy in the human brain in vivo and analyzed using a mathematical model to determine metabolic rates in human grey matter and white matter. 22.5-cc and 56-cc voxels were examined for grey matter and white matter, respectively. When partial volume effects were ignored, the measured tricarboxylic acid cycle rate was 0.72+/-0.22 (mean +/- SD) and 0.29+/-0.09 micromol min(-1) g(-1) (mean +/- SD) in voxels of approximately 70% grey and approximately 70% white matter, respectively. After correction for partial volume effects using a model with two tissue compartments, the tricarboxylic acid cycle rate in pure grey matter was higher (0.80+/-0.10 mol min(-1) g(-1); mean +/- SD) and in white matter was significantly lower (0.17+/-0.01 micromol min(-1) g(-1); mean +/- SD). In 1H-observed/13C-edited magnetic resonance spectroscopy labeling studies, the larger concentrations of labeled metabolites and faster metabolic rates in grey matter biased the measurements heavily toward grey matter, with labeling time courses in 70% grey matter appearing nearly identical to labeling in pure grey matter.

Brain↗

PubMed1999

Ketosis and epilepsy: 31P spectroscopic imaging at 4.1 T.

PURPOSE: To determine whether changes in the high-energy phosphates occur with use of the ketogenic diet in patients with intractable epilepsy. METHODS: 31P magnetic resonance spectroscopic imaging studies were performed at 4.1 T in seven patients with intractable epilepsy (four Lennox-Gastaut syndrome, one absence, one primary generalized tonic-clonic, and one partial complex) before and after institution of the ketogenic diet. Coronal 1H anatomic imaging also was performed to provide correlation to the 31P data. RESULTS: Taking the patients as a group, the ratio of phosphocreatine (PC)/gamma-adenosine triphosphate (ATP) measured at baseline (regular diet) compared with that measured after the ketogenic diet showed a small but significant increase from 0.61+/-0.08 to 0.69+/-0.08 (p < 0.05). Comparing the ratio of PCr inorganic phosphorus (Pi) measured at baseline with the postketogenic diet, there was a significant increase from 2.45+/-0.27 to 2.99+/-0.44 (p < 0.05). CONCLUSIONS: As a group, improvement of energy metabolism occurs with use of the ketogenic diet. This is in agreement with the chronic ketosis studies performed earlier in rodents.

Adenosine Triphosphate↗

PubMed1999

Rett syndrome: 1H spectroscopic imaging at 4.1 Tesla.

Rett syndrome, a neurodevelopmental disorder predominantly affecting girls, is characterized by regression of psychomotor development, communication dysfunction, and hand stereotypies. Brain morphologic studies demonstrate increased neuronal packing density and reduced dendritic arborizations, suggesting an arrest or interruption of normal maturation. Numerous neurotransmitter systems have been implicated. Among these, cerebrospinal fluid glutamate levels are elevated and glutamate receptors, particularly in putamen, are reduced. Therefore, 1H spectroscopy at 4.1 Tesla was used to evaluate glutamate, creatine, and N-acetylaspartate in six girls with Rett syndrome and four normal sibling controls. The ratio of creatine to N-acetylaspartate was significantly elevated in white matter, primarily reflecting reduced N-acetylaspartate levels, and normal in gray matter. The glutamate to N-acetylaspartate ratio was elevated in gray matter and normal in white matter. These findings are consistent with previous neuropathologic and neurochemical findings and indicate the feasibility of imaging these metabolites in vivo.

Aspartic Acid↗

PubMed1998

Measurements of human cerebral GABA at 4.1 T using numerically optimized editing pulses.

The goal of this work was to develop and evaluate a numerically optimized inversion pulse to be used with a homonuclear editing sequence to measure human cerebral GABA in vivo at 4.1 T in the occipital lobe. The optimized pulse was constructed using pallindromic symmetry with 30 pulses and 29 delays. The optimized pulse provided greater selectivity than the equivalent bandwidth matched DANTE pulse and sinc shaped DANTE. The improved selectivity reduced the co-editing of the macromolecule resonance, permitting the GABA edited doublet to be resolved in vivo. Using cerebral creatine as a reference, 7.1 mM, the measured GABA level was 1.15 +/- 0.13 mM in the occipital lobe.

Humans↗

PubMed1998

Quantitative spectroscopic imaging of the human brain.

A method to provide B1 correction and cerebrospinal fluid (CSF) referencing is developed and applied to spectroscopic imaging of the human brain at 4.1 T using a volume head coil. The B1 image allows rapid determination of the spatially dependent B1 that is then used to compensate for the B1 sensitivity of the spectroscopic sequence. The reference signal is acquired from CSF located in a lateral ventricular position using a point-resolved echo spectroscopy (PRESS) acquisition. The CSF spectrum is also corrected for B1 dependence. Together with T2 and T1 corrections, this method is used to provide quantitative values of N-acetylaspartate (NAA), creatine (Cr), and choline (Ch). The metabolite concentrations obtained from a spectroscopic imaging slice through the ventricles in seven normal controls are in good agreement with previously published literature values. This method is applied in a patient with secondary progressive multiple sclerosis, showing separate areas of abnormalities in both NAA and Cr.

Aspartic Acid↗

PubMed1997

Biological and clinical MRS at ultra-high field.

The advantages of performing spectroscopic studies at higher field strengths include increased SNR, improved spectral resolution for J-coupled resonances, and improvements in the selectivity of spectral editing schemes. By using pulse sequences that minimize the required echo time, refocus J-evolution, employ low peak B1 requiring pulses and take advantage of spectroscopic imaging methods, these advantages can also be utilized in clinical applications of spectroscopy at high field. In addition to the static measurements measurements of N-acetyl aspartate (NAA), creatine (CR) and choline (CH) which can be performed at 1.5 T, high resolution measurements of glutamate, glutamine, GABA and the incorporation of 13C labeled glucose into glutamate are possible with improved spatial and spectral resolution. These methods have been utilized in patients with seizure disorders and multiple sclerosis to identify, characterize and map the metabolic changes associated with these diseases and their treatment.

Brain↗

PubMed1997

13C editing of glutamate in human brain using J-refocused coherence transfer spectroscopy at 4.1 T.

The method of single quantum 13C editing is analyzed and implemented with water suppressed J-refocused coherence transfer spectroscopy. Analysis of the 13C inversion pulse demonstrates that it is optimally placed into the second echo of the J-refocused sequence. We have used this method to acquire 13C-edited spectra of glutamate from phantoms and in vivo. The turnover of 13C4-labeled glutamate in human brain in vivo was observed in parasagittal gray matter using a volume head coil at 4.1 T with a time resolution of 5.3 min.

Brain↗

PubMed1997

Thalamic thought disorder: on being "a bit addled".

Humans can generate and maintain relatively coherent trains of thought in natural discourse. The neural mediation of this ability and the phenomenology of its breakdown are not well understood. We report a case of a woman with paramedian thalamic strokes involving the mammillothalamic tract, intralaminar nuclei, parts of the dorsomedial and ventral lateral nuclei bilaterally. She presented with a dense amnesia and confusion typical of the syndrome of bilateral paramedian thalamic infarcts. Her Tc-99m HMPAO brain SPECT scan showed decreased thalamic and basal ganglia blood flow. General diminution of cerebral blood flow and areas of further diminution in the right frontal, left temporal and left temporoparietal regions were also observed. Although her amnesia was characteristic of diencephalic amnesia, her most striking clinical feature was a bizarre, disconnected and at times incoherent speech output. Analysis of her speech revealed relatively preserved lexical and morpho-syntactic linguistic production. By contrast, analysis of the macrostructure of her discourse revealed frequent unpredictable topic shifts that were completely unconstrained by contextual factors. Many of her shifts were intrusions from previous topics. We interpret her severely disordered speech output as representing the surface manifestations of a thought disorder (rather than as a language disorder per se) characterized by an inability to maintain and appropriately shift themes that normally guide discourse. Median and intralaminar thalamic nuclei appear to be critical for the neurophysiologic regulation of thalamocortical and striatocortical circuits, which in turn may be critical for the functional regulation of contextually appropriate transitions of thought.

Aged↗

PubMed1997

Studies of polymorphic DNA fingerprinting and lipid pattern of Mycobacterium tuberculosis patient isolates in Japan.

Strain differentiation by DNA restriction fragment length polymorphism (RFLP) has been used mainly for the epidemiological purpose of Mycobacterium tuberculosis infection. In this study, we tried to connect the molecular and phenotypic characteristics of M. tuberculosis patient isolates by comparing the DNA fingerprints obtained by RFLP using IS6110 and lipid patterns using two-dimensional thin-layer chromatography (2-D TLC) with silica gel, since M. tuberculosis has a lipid-rich cell envelope which contributes to the virulence and immunomodulatory properties. We found that 66 isolates of M. tuberculosis from tuberculosis patients showed that the occurrence of IS6110 varied from 1 to 24 copies. The IS6110 patterns were highly variable among isolates. Fifty different RFLP patterns were observed, and 12 RFLP patterns were shared by two or more strains. By computerized analysis of the RFLP patterns of M. tuberculosis patient isolates, we found that 95% of the isolates fell into seven clusters, from A to G, with at least two isolates in each (> 30% similarity). Among the cellular lipids, the phospholipid composition did not differ by strain, whereas the glycolipid pattern differed markedly. Especially, the relative concentration of cord factor and sulfolipid, both of which were known as virulent factors, varied by strain. The fingerprints of some strains showed an association between the DNA and glycolipid patterns, even though some of the same DNA fingerprint strains showed differences in lipid patterns. Among the patient isolates, M. tuberculosis strain 249 possessed a specific glycolipid with 2-O-methyl-L-rhamnose and L-rhamnose, which is rarely found in other strains. This glycolipid showed serological activity against the sera of tuberculosis patients, even if the reactivity was not as strong as trehalose dimycolate. It also showed the inhibition of phagosome-lysosome fusion in macrophages, suggesting involvement with virulence. These results suggest that RFLP analysis using IS6110 is useful for clustering the human isolates of M. tuberculosis, however, for further strain differentiation on virulence, a lipid analysis provides more information.

Antibodies, Bacterial↗

PubMed1996

Spectroscopic imaging of human brain glutamate by water-suppressed J-refocused coherence transfer at 4.1 T.

The authors reported the development and implementation of a water-suppressed J-refocused coherence transfer sequence to observe glutamate in human brain at 4.1 T. The sequence is modeled for I2S2 and I2S2M spin systems analytically and plotted for a range of echo times. In this sequence, water suppression and refocusing of J-coupled resonances are achieved through a brief multiple quantum step without significant loss of signal. Phantom data are shown. Human brain spectroscopic imaging of glutamate, acquired with a total echo of 36 ms, demonstrates the application of the sequence to observe gray and white matter differences in glutamate content.

Aspartic Acid↗

PubMed1996

Quantitative 1H spectroscopic imaging of human brain at 4.1 T using image segmentation.

Metabolic differences in the content of N-acetylaspartate (NAA), creatinine (CR), and choline (CH) in cerebral gray and white matter can complicate the interpretation of 1H spectroscopic images. To account for these variations, the gray- and white-matter content of each voxel must be known. To provide these data, a T1-based image segmentation scheme was implemented at 4.1 T. The tissue composition of each voxel was determined using the point-spread function of the spectroscopic imaging acquisition and the segmented anatomical image. Pure gray- and white-matter values for CR/NAA and CH/NAA, and the content of CR, CH, and NAA, were determined using a linear-regression analysis of 984 voxels acquired from 10 subjects using white-matter CR as an internal standard. This information was used to establish means and confidence intervals for CR/NAA and CH/NAA from a voxel of arbitrary tissue composition. Using a single-tailed t test, the extent and locations of the metabolic abnormalities (P < 0.05) in a patient with multiple sclerosis were identified.

Aspartic Acid↗

PubMed1996

Evaluation of multiple sclerosis by 1H spectroscopic imaging at 4.1 T.

The authors report on high-field (4.1 T) magnetic resonance 1H spectroscopic imaging studies on eight patients with relapsing remitting multiple sclerosis (mean expanded disability status scale (EDSS) 1.0) and eight normal controls. Using T1-weighted imaging to determine lesion position, the authors found the ratios of choline/N-acetyl (NA) compounds and creatine/NA were increased significantly in the multiple sclerosis (MS) patients relative to controls in lesioned tissue, adjacent to lesion, far removed from lesions as well as in periventricular tissue. The gray matter creatine/NA was mildly increased (P < 0.01) in the MS patients, whereas the elevated gray-matter ratio of choline/NA was of borderline significance (P = 0.13). A more detailed comparison of white-matter and mean gray-matter metabolite values indicates that creatine is increased greatest in areas far from lesions. This is in contrast to choline, which was greatest in lesions, and NA, which was smallest in lesions. It is postulated that the creatine increase may reflect an astrocytic (gliotic) or oligodendrocytic remyelinating process. The increased choline most likely reflects varying levels of inflammation and membrane turnover, whereas the NA decrease is representative of axonal dysfunction or loss.

Adult↗

PubMed1995

3D 31P spectroscopic imaging of the human heart at 4.1 T.

High field (4 Tesla) spectroscopic imaging offers the advantages of increased signal-to-noise ratio and the possibility of acquiring high resolution metabolite images. We have applied a three dimensional spectroscopic imaging sequence using a sparse Gaussian sampling method to acquire phosphocreatine (PCr) images of the human heart with 8-cc voxels. PCr images enabled observation of the septum, left ventricular free wall, apex, and skeletal muscle. Quantitative evaluation of the 50 myocardial voxels acquired from 10 studies of healthy adults revealed a PCr/adenosine triphosphate (ATP) ratio of 1.80 +/- 0.32 after correction for saturation effects. Due to the small size of the voxels and the ability to choose the location of the volumes to minimize inclusion of blood, no correction for blood pool ATP was required. The calculated PCr/ATP ratio is in agreement with other studies at 1.5 and 4.0 T.

Adenosine Triphosphate↗

PubMed1995

High resolution neuroimaging at 4.1T.

In this article we report on acquisition of high resolution 512 x 512 images at 4.1T using an inversion recovery gradient-echo sequence and a volume head coil developed for high field applications. The Ti values for cerebral white and grey matter were measured to be 834 and 1282 ms, respectively. The partial saturation inversion recovery sequence (Tir 800 ms and TR 2500 ms) provided excellent contrast-to-noise for white to grey matter. Consequently, the images consistently visualized the thalamic nuclear groups, hippocampal fine structure, as well as small draining vessels of the white matter.

Brain↗

PubMed1995

Application of high field spectroscopic imaging in the evaluation of temporal lobe epilepsy.

Previous spectroscopic imaging studies of temporal lobe epilepsy have used comparisons of metabolite content or ratios to lateralize the seizure focus. Although highly successful, these studies have shown significant variations within each of the groups of healthy subjects and patients. This variation may arise from the natural differences seen in metabolite concentration in gray and white matter, the complex anatomy seen about the hippocampus, and the large voxels typically employed at 1.5 T. Using a 4.1 T whole body system, we have acquired spectroscopic images with 0.5 cc nominal voxels (1 cc after filtering) to evaluate the regional variation in metabolite content of the hippocampus, temporal gray and white matter, midbrain, and cerebellar vermis. Using a threshold value of 0.90 for CR/NAA, a value 90% of all normal hippocampal voxels lay below, we have correctly identified the presence of epileptogenic tissue in patients with unilateral as well as bilateral seizures. By using comparisons to healthy values of the CR/NAA ratio, this method enables the visualization of bilateral disease and provides information on the extent of gray matter involvement.

Aspartic Acid↗

PubMed1994

Detection of brain glutamate and glutamine in spectroscopic images at 4.1 T.

Brain glutamate and glutamine were detected in healthy human volunteers in spectroscopic images with a nominal voxel size of 2.25 cm3 at an echo time of 15 ms. Due to the increased frequency separation and simplification of J-coupling patterns, the separate detection of brain glutamate and glutamine at short echo times was possible. Creatine, choline, and N-acetylaspartate with other N-acetylated compounds were also detected. The ratios of the metabolite resonance intensities were in agreement with previously published values.

Brain↗

PubMed1994

High frequency volume coils for clinical NMR imaging and spectroscopy.

A tuned transmission line resonator has been developed in theory and in practical design for the clinical NMR volume coil application at 4.1 tesla. The distributed circuit transmission line resonator was designed for high frequency, large conductive volume applications where conventional lumped element coil designs perform less efficiently. The resonator design has made use of a resonant coaxial cavity, which could be variably tuned to the Larmor frequency of interest by tunable transmission line elements. Large head- and body-sized volumes, high efficiencies, and broad tuning ranges have been shown to be characteristic of the transmission line resonator to frequencies of 500 MHz. The B1 homogeneity of the resonator has been demonstrated to be a function of the electromagnetic properties of the load itself. By numerically solving Maxwell's equations for the fully time-dependent B1 field, coil homogeneity was predicted with finite-element models of anatomic structure, and inhomogeneities corrected for. A how-to exposition of coil design and construction has been included. Simple methods of quadrature driving and double tuning the transmission line resonator have also been presented. Human head images obtained with a tuned transmission line resonator at 175 MHz have clearly demonstrated uncompromised high field advantages of signal-to-noise and spatial resolution.

Brain↗

PubMed1994

2D 1H spectroscopic imaging of the human brain at 4.1 T.

A two-dimensional spectroscopic imaging sequence consisting of an inversion recovery pulse, a plane selective prefocused pulse, and a semiselective water suppression pulse has been used to create 1H spectroscopic images of the human brain with nominal voxels of 0.5 cc. Due to the excellent lipid suppression provided by the inversion recovery pulse and subsequent delay, only planar volume selection is required enabling the entire brain within the slice to be imaged without contamination from extracerebral lipids in the brain voxels. The use of a semiselective refocusing pulse for water suppression permits any echo evolution time to be used, minimizing J-modulation and T2 losses, while retaining full sensitivity in the lactate resonance. Using this sequence we have visualized the lactate elevation in the peri-infarct region about a 6-week-old stroke.

Brain↗