Biomedical subjects

Truman R Brown

Publications and source records attributed to Truman R Brown.

13 recordsLinked to original sources

PubMed2006

Validation and optimization of statistical approaches for modeling odorant-induced fMRI signal changes in olfactory-related brain areas.

Recent neuroimaging studies have converged to show that odorant-induced responses to prolonged stimulation in primary olfactory cortex (POC) are characterized by a rapidly habituating time course. Different statistical approaches have effectively modeled this time course. One approach explicitly modeled rapid habituation using an exponentially decaying reference waveform that decreased to baseline levels within 30 to 40 s. A second approach modeled an early transient response by simply shortening the odorant 'ON' period to be less than the actual stimulation period (i.e., 9 of 40 s). The goal of the current study was to validate, compare, and optimize these methodological approaches by applying them to an olfactory fMRI block-design dataset from 10 healthy young subjects presented with odorants for 12 s (ON), alternating with 30 s of clear air (OFF). Both approaches significantly improved sensitivity to odorant-induced signal changes in POC relative to a square-wave model based on the actual stimulation period. Our findings further demonstrate that the 'optimal' model fit to the data was achieved by shortening the odorant 'ON' period to approximately 6 s. These results suggest that sensitivity to odorant-induced POC activity in block-design experiments can be optimized by modeling an early phasic response followed by a precipitous rather than specific exponential decrease to baseline levels. Notably, whole brain voxel-wise analyses further established that modeling rapid habituation in this way is not only sensitive, but also highly specific to odorant-induced activation in a well-established network of olfactory-related brain areas.

Adult↗

PubMed2006

HiRes--a tool for comprehensive assessment and interpretation of metabolomic data.

UNLABELLED: The increasing role of metabolomics in system biology is driving the development of tools for comprehensive analysis of high-resolution NMR spectral datasets. This task is quite challenging since unlike the datasets resulting from other 'omics', a substantial preprocessing of the data is needed to allow successful identification of spectral patterns associated with relevant biological variability. HiRes is a unique stand-alone software tool that combines standard NMR spectral processing functionalities with techniques for multi-spectral dataset analysis, such as principal component analysis and non-negative matrix factorization. In addition, HiRes contains extensive abilities for data cleansing, such as baseline correction, solvent peak suppression, removal of frequency shifts owing to experimental conditions as well as auxiliary information management. Integration of these components together with multivariate analytical procedures makes HiRes very capable of addressing the challenges for assessment and interpretation of large metabolomic datasets, greatly simplifying this otherwise lengthy and difficult process and assuring optimal information retrieval. AVAILABILITY: HiRes is freely available for research purposes at http://hatch.cpmc.columbia.edu/highresmrs.html

Algorithms↗

PubMed2005

Total homocysteine is associated with white matter hyperintensity volume: the Northern Manhattan Study.

BACKGROUND: Total homocysteine (tHcy) has been implicated as a risk factor for stroke and dementia, but the mechanism is unclear. White matter hyperintensities may be a risk factor for both, but studies of the relationship between tHcy and quantitative measures of white matter hyperintensity volume (WMHV) are lacking, especially in minority populations. METHODS: A community-based sample of 259 subjects with baseline tHcy levels underwent pixel-based quantitative measurement of WMHV. We examined the relationship between tHcy and WMHV adjusting for age, sociodemographics, vascular risk factors, and B12 deficiency. RESULTS: Higher levels of tHcy were associated with WMHV adjusting for sociodemographics and vascular risk factors. CONCLUSIONS: These cross-sectional data provide evidence that tHcy is a risk factor for white matter damage.

Aged↗

PubMed2005

Methods for noninvasive measurement of tissue iron in Cooley's anemia.

To examine the relationship between myocardial storage iron and body iron burden, as assessed by hepatic storage iron measurements, we studied 22 patients with transfusion-dependent thalassemia syndromes, all being treated with subcutaneous deferoxamine, and 6 healthy subjects. Study participants were examined with a Philips 1.5-T Intera scanner using three multiecho spin echo sequences with electrocardiographic triggering and respiratory navigator gating. Myocardial and hepatic storage iron concentrations were determined using a new magnetic resonance method that estimates total tissue iron stores by separately measuring the two principal forms of storage iron, ferritin and hemosiderin. In a subset of 10 patients with beta-thalassemia major, the hepatic storage iron concentration had been monitored repeatedly for 12-14 years by chemical analysis of tissue obtained by liver biopsy and by magnetic susceptometry. In this subset, we examine the relationship between hepatic iron concentration over time and our current magnetic resonance estimates of myocardial iron stores. No significant relationship was found between simultaneous estimates of myocardial and hepatic storage iron concentrations. By contrast, in the subset of 10 patients with beta-thalassemia major, the correlation between the 5-year average of hepatic iron concentration and the current myocardial storage iron was significant (R = .67, P = .03). In these patients, myocardial storage iron concentrations seem to reflect the control of body iron over a period of years. Magnetic resonance methods promise to provide more effective monitoring of iron deposition in vulnerable tissues, including the liver, heart, and endocrine organs, and could contribute to the development of iron-chelating regimens that more effectively prevent iron toxicity.

Adult↗

PubMed2004

Sample classification based on Bayesian spectral decomposition of metabonomic NMR data sets.

1H NMR spectra of biofluids provides a wealth of biochemical information on the metabolic status of an organism. Through the application of pattern recognition and classification algorithms, the data have been shown to provide information on disease diagnosis and the beneficial and adverse effects of potential therapeutics. Here, a novel approach is described for identifying subsets of spectral patterns in databases of NMR spectra, and it is shown that the intensities of these spectral patterns can be related to the onset and recovery from a toxic lesion in both a time-related and dose-related fashion. These patterns form a new type of combination biomarker for the biological effect under study. The approach is illustrated with a study of liver toxicity in rats using NMR spectra of urine following administration of a model hepatotoxin hydrazine.

Animals↗

PubMed2004

Normalization of single-channel DNA array data by principal component analysis.

MOTIVATION: Detailed comparison and analysis of the output of DNA gene expression arrays from multiple samples require global normalization of the measured individual gene intensities from the different hybridizations. This is needed for accounting for variations in array preparation and sample hybridization conditions. RESULTS: Here, we present a simple, robust and accurate procedure for the global normalization of datasets generated with single-channel DNA arrays based on principal component analysis. The procedure makes minimal assumptions about the data and performs well in cases where other standard procedures produced biased estimates. It is also insensitive to data transformation, filtering (thresholding) and pre-screening.

Algorithms↗

PubMed2004

Automatic alignment of individual peaks in large high-resolution spectral data sets.

Pattern recognition techniques are effective tools for reducing the information contained in large spectral data sets to a much smaller number of significant features which can then be used to make interpretations about the chemical or biochemical system under study. Often the effectiveness of such approaches is impeded by experimental and instrument induced variations in the position, phase, and line width of the spectral peaks. Although characterizing the cause and magnitude of these fluctuations could be important in its own right (pH-induced NMR chemical shift changes, for example) in general they obscure the process of pattern discovery. One major area of application is the use of large databases of (1)H NMR spectra of biofluids such as urine for investigating perturbations in metabolic profiles caused by drugs or disease, a process now termed metabonomics. Frequency shifts of individual peaks are the dominant source of such unwanted variations in this type of data. In this paper, an automatic procedure for aligning the individual peaks in the data set is described and evaluated. The proposed method will be vital for the efficient and automatic analysis of large metabonomic data sets and should also be applicable to other types of data.

Animals↗

PubMed2004

Predicting treatment response in non-Hodgkin's lymphoma from the pretreatment tumor content of phosphoethanolamine plus phosphocholine.

RATIONALE AND OBJECTIVES: Phosphoethanolamine and phosphocholine, shown to be elevated in tumors and possibly related to apoptotic signaling, have the potential to be prognostic variables of cancer treatment. MATERIALS AND METHODS: The sum of phosphoethanolamine and phosphocholine normalized by nucleotide-triphosphates was determined in tumors of non-Hodgkin's lymphoma (NHL) patients via in vivo 31P MR spectroscopy. RESULTS: The normalized sum of phosphoethanolamine and phosphocholine showed significant differences in tumors of patients who had a complete response to treatment against those who did not (t-test: 1.45 +/- 0.15, mean +/- standard error, n = 10 vs. 2.28 +/- 0.15, n = 17, P < .001; Fisher test: P < .04; sensitivity and specificity approximately equal to 70%). This parameter also showed significant differences among treatment responses in the previously untreated and aggressive subgroups and in the low and low-intermediate-risk subgroups determined by the international prognostic index (IPI). Further, distinctly different treatment response cutoffs for the parameter were found in different risk groups. When these risk-dependent cutoffs were used, the Fisher test of the whole group improved (P < .0002, sensitivity 80%, specificity 94%). The normalized sum of phosphoethanolamine and phosphocholine and the IPI were better predictor covariates for time to treatment failure when fitted interactively in a Cox regression (P < .0003) than when fitted independently. When time to treatment failure was used as a surrogate of survival in Kaplan-Meier analysis, the interaction of both covariates segregated the cases significantly (P < .008). There was no significance with each covariate independently. CONCLUSION: The normalized sum of phosphoethanolamine and phosphocholine measured before treatment successfully predicts long-term response to treatment and time to treatment failure in non-Hodgkin's lymphoma, particularly when combined with the IPI.

Chi-Square Distribution↗

PubMed2004

Detection of fetal lactate with two-dimensional-localized proton magnetic resonance spectroscopy.

BACKGROUND: Antenatal surveillance is inefficient for accurately detecting fetal compromise. A noninvasive technique for assessing fetal metabolic status would be useful for clinical management. CASE: Fetal magnetic resonance spectroscopy was performed at 20 weeks in a pregnancy complicated by severe intrauterine growth restriction to determine if lactate, a metabolite associated with fetal hypoxia, was present. Two-dimensional, single-slice proton magnetic resonance spectroscopy was carried out at 1.5 T using a volume-selective, double-spin echo technique. Lactate was detected in fetal back muscle. Fetal death occurred the next day. CONCLUSIONS: Although this initial report is purely experimental, further development of this technique may prove to be a valuable noninvasive tool in the management of suspected fetal hypoxia.

Adult↗

PubMed2004

Nonnegative matrix factorization for rapid recovery of constituent spectra in magnetic resonance chemical shift imaging of the brain.

We present an algorithm for blindly recovering constituent source spectra from magnetic resonance (MR) chemical shift imaging (CSI) of the human brain. The algorithm, which we call constrained nonnegative matrix factorization (cNMF), does not enforce independence or sparsity, instead only requiring the source and mixing matrices to be nonnegative. It is based on the nonnegative matrix factorization (NMF) algorithm, extending it to include a constraint on the positivity of the amplitudes of the recovered spectra. This constraint enables recovery of physically meaningful spectra even in the presence of noise that causes a significant number of the observation amplitudes to be negative. We demonstrate and characterize the algorithm's performance using 31P volumetric brain data, comparing the results with two different blind source separation methods: Bayesian spectral decomposition (BSD) and nonnegative sparse coding (NNSC). We then incorporate the cNMF algorithm into a hierarchical decomposition framework, showing that it can be used to recover tissue-specific spectra given a processing hierarchy that proceeds coarse-to-fine. We demonstrate the hierarchical procedure on 1H brain data and conclude that the computational efficiency of the algorithm makes it well-suited for use in diagnostic work-up.

Algorithms↗

PubMed2002

Phosphomonoester concentrations differ between chronic lymphocytic leukemia cells and normal human lymphocytes.

Levels of phospholipid-related metabolites of chronic lymphocytic leukemia lymphocytes (CLL) and normal human lymphocytes were quantified using phosphorus magnetic resonance spectroscopy. The CLL cells versus normal lymphocytes showed significant increases of phosphoethanolamine(Etn-P) (8.11+/-2.10 mean+/-S.E., micromol/g wet weight, n=12 versus 3.63+/-1.10, n=3, P<or=0.002), phosphocholine (2.10+/-0.37, n=12 versus 0.36+/-0.09, n=3, P<or=0.01), glycerophosphoethanolamine (0.26+/-0.03, n=10 versus 0.11+/-0.05, n=3, P<or=0.004), and glycerophosphocholine (0.33+/-0.03, n=10 versus 0.17+/-0.05, n=3, P<or=0.003). Further, the phospholipid precursor ethanolamine (Eth) was studied in blood and was found significantly lowered in CLL patients (4.6+/-1.6 microM, n=25) compared to normal volunteers (7.7+/-2.5, n=12, P<or=0.001). Increased intermediates with depletion of precursors suggest the presence of sustained phospholipid metabolism activation in CLL.

Adult↗

PubMed2002

Prediction of treatment response of head and neck cancers with P-31 MR spectroscopy from pretreatment relative phosphomonoester levels.

RATIONALE AND OBJECTIVES: Combinations of chemotherapy and fractionated radiation therapy are the currently preferred nonsurgical treatment methods for squamous cell carcinoma of the head and neck, but to the authors' knowledge there is no reliable marker for predicting therapeutic response. Early identification of nonresponders would allow prompt replacement of ineffective, toxic therapy by alternative, potentially more effective procedures. Frequent regional node involvement facilitates surface coil investigation with phosphorus-31 magnetic resonance spectroscopy. MATERIALS AND METHODS: P-31 magnetic resonance spectra were acquired from 12 patients before radiation therapy or chemotherapy. In vivo three-dimensional localized P-31 nuclear magnetic resonance chemical shift imaging was performed with a 1.5-T clinical imager and a dual-tuned H-1/P-31 surface coil. Proton decoupling and nuclear Overhauser enhancement were used to improve sensitivity and resolve overlapping signals in the phosphomonoester region of the spectrum. RESULTS: The average pretreatment ratio of phosphomonoester to beta-nucleoside triphosphate was significantly smaller in complete responders (n = 4) than in incomplete responders (partial responders plus nonresponders, n = 8) (0.0 +/- 0.0 vs 1.22 +/- 0.17 [P = .004]). CONCLUSION: Results of this preliminary study suggest that H-1-decoupled P-31 magnetic resonance spectroscopy may prove to be a useful predictor of therapeutic response in head and neck cancers.

Adult↗

PubMedDate not supplied

In vivo measurement of phosphorous markers of disease.

Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) has been utilized to study energy, carbohydrate, and phospholipid metabolism in vitro and in vivo in live tissues non-invasively. Despite its lack of sensitivity, its application has extended to in situ human tissues and organs since proper signal localization was devised. Follow-up of phosphocreatine in neuromuscular diseases and schizophrenia and follow-up of phospholipid-related molecules in tumors are described here to demonstrate the value of 31P-MRS as an imaging technique to determine in vivo markers of disease and in the diagnosis, prognosis, and follow-up of human diseases.

Biomarkers, Tumor↗