Biomedical subjects

Leo L Cheng

Publications and source records attributed to Leo L Cheng.

6 recordsLinked to original sources

PubMed2005

Metabolic characterization of human prostate cancer with tissue magnetic resonance spectroscopy.

Diagnostic advancements for prostate cancer have so greatly increased early detections that hope abounds for improved patient outcomes. However, histopathology, which guides treatment, often subcategorizes aggressiveness insufficiently among moderately differentiated Gleason score (6 and 7) tumors (>70% of new cases). Here, we test the diagnostic capability of prostate metabolite profiles measured with intact tissue magnetic resonance spectroscopy and the sensitivity of local prostate metabolites in predicting prostate cancer status. Prostate tissue samples (n = 199) obtained from 82 prostate cancer patients after prostatectomy were analyzed with high-resolution magic angle spinning proton magnetic resonance spectroscopy, and afterwards with quantitative pathology. Metabolite profiles obtained from principal component analysis of magnetic resonance spectroscopy were correlated with pathologic quantitative findings by using linear regression analysis and evaluated against patient pathologic statuses by using ANOVA. Paired t tests show that tissue metabolite profiles can differentiate malignant from benign samples obtained from the same patient (P < 0.005) and correlate with patient serum prostate-specific antigen levels (P < 0.006). Furthermore, metabolite profiles obtained from histologically benign tissue samples of Gleason score 6 and 7 prostates can delineate a subset of less aggressive tumors (P < 0.008) and predict tumor perineural invasion within the subset (P < 0.03). These results indicate that magnetic resonance spectroscopy metabolite profiles of biopsy tissues may help direct treatment plans by assessing prostate cancer pathologic stage and aggressiveness, which at present can be histopathologically determined only after prostatectomy.

Humans↗

PubMed2005

Reduction of spinning sidebands in proton NMR of human prostate tissue with slow high-resolution magic angle spinning.

High-resolution magic angle spinning (HRMAS) NMR spectroscopy has proven useful for analyzing intact tissue and permitting correlations to be made between tissue metabolites and disease pathologies. Extending these studies to slow-spinning methodologies helps protect tissue pathological structures from HRMAS centrifuging damage and may permit the study of larger objects. Spinning sidebands (SSBs), which are produced by slow spinning, must be suppressed to prevent the complication of metabolic spectral regions. In this study human prostate tissues, as well as gel samples of a metabolite mixture solution, were measured with continuous-wave (CW) water presaturation on a 14.1T spectrometer, with HRMAS spinning rates of 250, 300, 350, 600, and 700 Hz, and 3.0 kHz. Editing the spectra by means of a simple minimum function (Min(A, B, ..., N) for N spectra acquired at different but close spinning rates) produced SSB-free spectra. Statistically significant linear correlations were observed for metabolite concentrations quantified from the Min(A, B, ..., N)-edited spectra generated at low spinning rates, with concentrations measured from the 3 kHz spectra, and also with quantitative pathology. These results indicate the empirical utility of this scheme for analyzing intact tissue, which also may be used as an adjunct tool in pathology for diagnosing disease.

Algorithms↗

PubMed2005

Quantification of phosphocholine and glycerophosphocholine with 31P edited 1H NMR spectroscopy.

Choline and the related compounds phosphocholine (PC) and glycerophosphocholine (GPC) are considered to be important metabolites in oncology. Past studies have demonstrated correlations linking the relative ratios and concentrations of these metabolites with the development and progression of cancer. Currently, in vivo and tissue ex vivo magnetic resonance spectroscopy methods have mostly centered on measuring the total concentration of these metabolites and have difficulty in differentiating between them. Here, a new scheme that uses (31)P edited (1)H spectroscopy to quantify the concentrations of choline, PC and GPC in biological samples is reported and its applicability is demonstrated using samples of human brain tumor extracts. This method is particularly well-suited for analytical situations where the PC and GPC resonances are not sufficiently resolved and/or are obscured by other metabolites. Consequently, this scheme has the potential to be used for the analysis of choline compounds in ex vivo tissue samples.

Biomarkers, Tumor↗

PubMed2004

Quantitative pathology in tissue MR spectroscopy based human prostate metabolomics.

At present, the clinical utility of metabolomic profiles of human prostate tissue relies on the establishment of correlations between metabolite data and clinical measurements, particularly pathological findings. Because metabolomics is a quantitative study, its clinical value can be rigorously investigated by determining its association with other quantitative measures. The human visual assessment of prostate tissue, however, introduces both inter- and intra-observer biases that may limit the reliability of its quantitations, and therefore, the strength of its correlations with metabolomic profiles. The aim of this study was to develop a simple, feasible protocol for the computer-aided image analysis (CAIA) of prostate pathology slides in order to achieve quantitative pathology from tissue samples, following metabolomic measurement with high-resolution magic angle spinning (HRMAS) magnetic resonance spectroscopy (MRS). Thirty-eight samples from 29 prostatectomy cases were studied with HRMAS MRS. After spectroscopy analysis, samples were serial-sectioned, stained and visually assessed by pathologists. Cross-sections from these samples were then measured with the CAIA protocol. Results showed a two-fold difference between human visual assessments of the area percentages of tissue pathologies and CAIA area percentages obtained for the same features. Linear correlations were found between both metabolites indicative of normal epithelium and those indicative of prostate cancer, and the CAIA quantitative results. CAIA based quantitative pathology is more reliable than human visual assessment in establishing correlations useful for disease diagnosis between prostate pathology and metabolite concentrations.

Epithelium↗

PubMed2003

High-resolution magic angle spinning proton NMR analysis of human prostate tissue with slow spinning rates.

The development of high-resolution magic angle spinning (HR-MAS) NMR spectroscopy for intact tissue analysis and the correlations between the measured tissue metabolites and disease pathologies have inspired investigations of slow-spinning methodologies to maximize the protection of tissue pathology structures from HR-MAS centrifuging damage. Spinning sidebands produced by slow-rate spinning must be suppressed to prevent their complicating the spectral region of metabolites. Twenty-two human prostatectomy samples were analyzed on a 14.1T spectrometer, with HR-MAS spinning rates of 600 Hz, 700 Hz, and 3.0 kHz, a repetition time of 5 sec, and employing various rotor-synchronized suppression methods, including DANTE, WATERGATE, TOSS, and PASS pulse sequences. Among them, DANTE, as the simplest scheme, has shown the most potential in suppression of tissue water signals and spinning sidebands, as well as in quantifying metabolic concentrations.

Humans↗

PubMed2003

Proton high-resolution magic angle spinning NMR analysis of fresh and previously frozen tissue of human prostate.

The previously observed improvement in spectral resolution of tissue proton NMR with high-resolution magic angle spinning (HRMAS) was speculated to be due largely to freeze-thawing artifacts resulting from tissue storage. In this study, 12 human prostate samples were analyzed on a 14.1T spectrometer at 3 degrees C, with HRMAS rates of 600 and 700 Hz. These samples were measured fresh and after they were frozen for 12-16 hr prior to thawing. The spectral linewidths measured from fresh and previously frozen samples were identical for all metabolites except citrate and acetate. The metabolite intensities of fresh and freeze-thawed samples depend on the quantification procedures used; however, in this experiment the differences of means were <30%. As expected, it was found that tissue storage impacts tissue quality for pathological analysis, and HRMAS conditions alone are not sufficiently destructive to impair pathological evaluation. Furthermore, although storage conditions affect absolute metabolite concentrations in NMR analysis, relative metabolite concentrations are less affected.

Cryopreservation↗