Chun-Wei Li

In vivo proton magnetic resonance spectroscopy of large focal hepatic lesions and metabolite change of hepatocellular carcinoma before and after transcatheter arterial chemoembolization using 3.0-T MR scanner.

To investigate the value of in vivo proton magnetic resonance spectroscopy (MRS) in the assessment of large focal hepatic lesions and to measure the metabolite change of hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE) using 3.0‐T scanner.

Quantification of choline compounds in human hepatic tumors by proton MR spectroscopy at 3 T

The quantification of choline‐containing compounds (Cho) in hepatic tumors by 1H MR spectroscopy (MRS) is of great interest because such compounds have been linked to malignancy. In this study, a practical external phantom replacement method for the absolute quantification of hepatic metabolites is demonstrated. We performed experiments at 3 T using a body coil, and used an external phantom containing choline chloride for calibration. We first tested the quantification strategy to confirm its suitability in vivo using a phantom of known concentration and normal brain tissue. The results obtained after coil loading and T1 and T2 effects were corrected for were consistent with the known concentration and previously published values. To demonstrate its feasibility, we applied the technique to liver studies conducted on five normal volunteers and four patients with hepatocellular carcinoma, and one patient (also in the latter group) who had undergone post‐transcatheter arterial chemoembolization (TACE). The Cho concentrations in the four patients were estimated to be 3.4, 6.3, 7.4, and 14.0 mM, respectively. These values are substantially higher than those obtained from the healthy volunteers (1.3 ± 0.9 mM (mean ± SD)). The results indicate that the proposed method is accurate and requires fewer tedious procedures for MRS; therefore, it may be a promising technique for evaluating response to treatment in liver cancer. Magn Reson Med 53:770–776, 2005.

Flow-through sampling for electrophoresis-based microfluidic chips using hydrodynamic pumping

This work presents a novel electrophoretic microchip design which is capable of directly coupling with flow-through analyzers for uninterrupted sampling. In this device, a 3 mm wide sampling channel (SC) was etched on quartz substrate to create the sample inlet and outlet and the 75 microm wide electrophoretic channels were also fabricated on the same substrate. Pressure was used to drive the sample flow through the external tube into the SC and the flow was then split into outlet and electrophoretic channels. A gating voltage was applied to the electrophoretic channel to control the sample loading for subsequent separations and inhibit the sample leakage. The minimum gating voltage required to inhibit the sample leakage depended on the solution buffer and increased with the hydrodynamic flow-rate. A fluorescent dye mixture containing Rhodamine B and Cy3 was introduced into the sample stream at either a continuous or discrete mode via an on-line injection valve and then separated and detected on the microchip using laser-induced fluorescence. For both modes, the relative standard deviation of migration time and peak intensity for consecutive injections was determined to be below 0.6 and 8%, respectively. Because the SC was kept floating, the external sampling equipment requires no electric connection. Therefore, such an electrophoresis-based microchip can be directly coupled with any pressure-driven flow analyzers without hardware modifications. To our best knowledge, this is something currently impossible for reported electrophoretic microchip designs.

Muscle metabolism in Duchenne muscular dystrophy assessed by in vivo proton magnetic resonance spectroscopy.

To investigate the correlation between muscle function and metabolism in muscle tissue of Duchenne muscular dystrophy (DMD) patients by in vivo proton magnetic resonance spectroscopy. Materials and Methods: In this prospective study, we enrolled 8 boys with DMD and 8 healthy volunteers. In vivo proton magnetic resonance spectroscopy of the soleus muscles was performed using a whole-body 3.0-Tesla imaging unit and a knee coil. The levels of trimethyl ammonium (TMA) and total creatine (tCr) were measured. We compared TMA/water, tCr/water, and TMA/tCr ratios, and scores for muscle function in the legs by using a t test. Results: Fat infiltrated the leg muscles in all patients but no volunteers. All patients had elevated creatine kinase levels. Magnetic resonance spectra of patients and volunteers showed TMA and tCr peaks. Ratios of TMA/water (P = 0.0015), tCr/water (P = 0.0167), and TMA/tCr (P = 0.0017), and muscle function scores (P = 0.0028) were significantly lower in patients than in volunteers. All patients had impaired muscle function, whereas all volunteers had normal function. Muscle function in the legs was negatively correlated with the TMA/tCr ratio (r2 = 0.878). Conclusions: Metabolite ratios and muscle function scores were significantly decreased in patients with DMD when compared with normal control subjects. A statistically significant decrease in TMA/tCr ratio in patients with DMD as compared with control subjects was found to correlate with decreased muscle function.

Proton magnetic resonance spectroscopy of late-life major depressive disorder

The primary goal of this study was to examine the biochemical abnormalities of late-life major depression by using 3-tesla (3-T) proton magnetic resonance spectroscopy ((1)H-MRS). The antidepressant effects on the biochemical abnormalities were investigated as well. Study participants were 27 elderly patients with major depressive disorders (among which 9 were on antidepressant medication) and 19 comparison elderly subjects. (1)H-MRS spectra were acquired from voxels that were placed in the left frontal white matter, left periventricular white matter, and left basal ganglia. Ratios of N-acetylaspartate (NAA), choline (Cho) and myo-inositol to creatine were calculated. Patients with late-life major depressive disorder had a significantly lower NAA/creatine ratio in the left frontal white matter, and higher Cho/creatine and myo-inositol/creatine ratios in the left basal ganglia when compared with the control subjects. The myo-inositol correlated with global cognitive function among the patients. The biochemical abnormalities in late-life major depressive disorder were found on the left side of the frontal white matter and the basal ganglia. Neuron degeneration in the frontal white matter and second messenger system dysfunction or glial dysfunction in the basal ganglia are suggested to be associated with late-life depression.

Longitudinally monitoring chemotherapy effect of malignant musculoskeletal tumors with in vivo proton magnetic resonance spectroscopy: an initial experience.

Purpose: To investigate the value of in vivo proton (1H) magnetic resonance spectroscopy (MRS) in longitudinally monitoring the treatment response of malignant musculoskeletal tumors under chemotherapy. Materials and Methods: Twenty-three studies in 3 patients with bone and soft-tissue tumors (2 lymphomas and 1 alveolar soft part sarcoma) were included in the study. The dynamic contrast-enhanced magnetic resonance (MR) imaging and single-voxel proton MRS with 135 milliseconds of echo time were carried out using a whole-body 1.5-T scanner and a surface coil. The volume of interest within the lesion was positioned on the area of early enhancement according to the finding of the first dynamic contrast-enhanced MR imaging with subtraction. The choline and water intensities were measured at the peak areas at 3.2 and 4.5 ppm. The choline-water ratios were calculated as well. Statistical analysis was performed by using Kruskal-Wallis 1-way analysis of variance test (Table 1). TABLE 1. Summary of MRS Findings of the 23 Follow-Up Studies in the 3 Patients Results The changes observed on the dynamic contrast-enhanced MR images and tumor size after chemotherapy fell into 2 clearly distinct patterns: subsequent partial response (patients 1 and 2) and progressive disease (patient 3). The choline concentration, choline-volume ratio, and choline-water ratio in the first 2 patients were reduced substantially to zero in the follow-up MRS. In the remaining patient, the choline, choline-volume ratio, and choline-water ratio remained high in the follow-up MRS. The water concentration and water-volume ratio between the 3 patients showed significant statistical differences (Kruskal-Wallis test, P = 0.004 and 0.039). Conclusion In vivo proton MRS is technically feasible for the evaluation of musculoskeletal tumors. Choline can be detected in malignant bone and soft-tissue tumors, and the early metabolite changes after chemotherapy can also be identified in the in vivo proton MRS by using a standard clinical-use 1.5-T MR scanner and a surface coil. The decline of choline after treatment in malignant bone and soft-tissue tumors correlates with the response of the dynamic contrast MR images and the tumor size. The information provided with MR imaging and proton MRS may improve the diagnostic specificity of MR examination in the follow-up of tumor treatment.

Brain Biochemical Correlates of the Plasma Homocysteine Level: A Proton Magnetic Resonance Spectroscopy Study in the Elderly Subjects

BACKGROUND An elevated plasma homocysteine level has been reported to be associated with various neuropsychiatric diseases. However, little is known about the brain biochemical changes associated with the higher plasma homocysteine level. The main goal of this study was to examine the sex difference in brain biochemical concentrations using brain proton magnetic resonance spectroscopy (H MRS), and to elucidate the biochemical changes associated with plasma homocysteine levels by sex in healthy elderly subjects. METHODS Seventy elderly subjects without any clinical psychiatric and neurological disease underwent 3-T brain H MRS. MRS spectra were acquired from voxels placed on the left side of the basal ganglia, frontal lobe, and hippocampus. Brain biochemical concentrations were compared between the elderly male and female participants. Correlations between these biochemical concentrations and plasma homocysteine levels by sex were analyzed. RESULTS Female participants had significantly higher levels of choline in the left frontal lobe and hippocampus, and lower creatine and myo-inositol, in the left basal ganglia than did males. A higher homocysteine level was correlated with a lower N-acetylaspartate (NAA) concentration in the left hippocampus in elderly women (r = -0.44; p = 0.03) but not in elderly men. CONCLUSIONS This study found that there was a sex difference in brain biochemical concentrations in the elderly participants. A higher plasma homocysteine level was associated with a lower NAA in the hippocampus of elderly women. The sex difference in association between brain biochemical concentrations and plasma homocysteine levels needs further investigation. We speculate that after menopause, women lose protection of estrogen from the neurotoxic effects of homocysteine in the hippocampus. Future studies are required to examine this speculation.

Heme protein assisted dispersion of gold nanoparticle multilayers on chips: From stabilization to high-density double-stranded DNAs fabricated in situ for protein/DNA binding

Heme proteins in general are shown to be an effective linking agent in stabilizing gold nanoparticles (AuNPs) and thus facilitate the fabrication of three-dimensional (3D) AuNP multilayers on a chip, resulting in a higher coating density than that on polymer linker anchored surfaces for analytical applications. With the use of electron spectroscopy for chemical analysis (ESCA) measurements, a lower oxidation state of Au(0) and dramatic changes among multiple chemical states of N1s are detected upon coating AuNPs with heme proteins but not detected upon coating AuNPs with non-heme proteins. Thus, we propose that the stabilization power arises from pi-conjugation between AuNPs and the heme group. We also propose that such conjugation must be facilitated by the exposure of the heme group through a conformational change of the protein as well as interactions of other functional groups with AuNPs to bring the heme moiety to a close face-to-face distance with the AuNPs. A high-density double-stranded DNA (dsDNA) composed of a sequence of estrogen response element (ERE) is then fabricated on heme protein anchored chips. An in situ hybridization and tracking method is developed based on hybridization-induced fluorescence restoration associated with AuNPs and assists in the subsequent detection of DNA/protein binding on the same chip. The AuNP ERE chips are shown to have high sensitivity and specificity for quantitative detection of ERE binding with its two transcription factor isoforms, estrogen receptors alpha and beta (ERalpha and ERbeta), in cell lysates with reduced reagents and reaction time.

A proton magnetic resonance spectroscopy study of the chronic lead effect on the Basal ganglion and frontal and occipital lobes in middle-age adults.

Background Lead is known to be a health hazard to the human brain and nervous system based on data from epidemiologic studies. However, few studies have examined the mechanism or biochemical changes caused by lead in the human brain, although recently some have used magnetic resonance spectroscopy (MRS) to test brain metabolism in vivo. Objectives In this study, we used 3-T MRS to investigate brain metabolism in workers chronically exposed to lead and matched nonexposed controls. Materials Methods: Twenty-two workers at a lead paint factory served as chronically exposed subjects of this study. These workers did not have any clinical syndromes. Eighteen age- and sex-matched nonexposed healthy volunteers served as controls. We measured blood and bone lead and used a 3-T MRS to measure their levels of brain N-acetyl aspartate (NAA), choline (Cho), and total creatine (tCr). A structural questionnaire was used to collect demographic, work, and health histories and information about their life habits. Results All the MRS measures were lower in the lead-exposed group. Increased blood and bone lead levels correlated with declines in Cho:tCr ratios, especially in the occipital lobe, where changes in all gray, subcortical, and white matter were significant. Increases in blood and patella lead in every layer of the frontal lobe correlated with significant decreases in NAA:tCr ratios. One of the strongest regression coefficients was −0.023 (SE = 0.005, p < 0.001), which was found in the NAA:tCr ratio of frontal gray matter. Discussion We conclude that chronic exposure to lead might upset brain metabolism, especially NAA:tCr and Cho:tCr ratios. Brain NAA and Cho are negatively correlated to blood and bone lead levels, suggesting that lead induces neuronal and axonal damage or loss. The most significant changes occurred in frontal and occipital lobes, areas in which previous neurobehavioral studies have shown memory and visual performance to be adversely affected by lead toxicity.

Evaluation of (Gd(Bz-TTDA)) 2- as a Potential Contrast Agent in MR Imaging of the Hepatobiliary System: An Animal Study

To evaluate the potential of a new lipophilic paramagnetic complex [Gd(Bz‐TTDA)]2– [(4s)‐4‐benzyl‐3,6,10‐tri(carboxymethyl)‐3,6,10‐triazadodecandioic acid]2– designed for use as a hepatobiliary MR contrast agent.