Biomedical subjects

Peter J Moate

Publications and source records attributed to Peter J Moate.

10 recordsLinked to original sources

PubMed2007

High frame-rate simultaneous bilateral breast DCE-MRI.

A simultaneous bilateral back-projection method for 3D dynamic contrast-enhanced (DCE)-MRI of the breasts was developed and evaluated. Using a double-side band modulation of the RF slab excitation pulse, discontinuous volumes that included both breasts were simultaneously selected. The number of slice phase-encoding steps was undersampled by a factor of 2, and the resulting signal aliasing from one volume to the other was removed using SENSE processing. In-plane encoding was performed with an interleaved radial acquisition reconstructed using dynamic k-space-weighted image contrast (KWIC) temporal filtering. Image resolution was 0.5 x 0.5 x 3.0 mm(3) with an effective temporal resolution of 15 s for both breast volumes. Combined with the 2x acceleration from SENSE encoding, this is a 16x acceleration factor over a conventional MR bilateral breast scan. An initial evaluation of these methods was performed on a cohort of women who presented with palpable or mammographically visible breast abnormalities. A total of 73 abnormalities were found in 45 of the 54 bilateral examinations that were performed. In 11 of these cases there was a significant finding in the contralateral breast. DCE images of both breasts can be acquired simultaneously, resulting in high-resolution images as well as rapid sampling of the contrast kinetics.

Breast↗

PubMed2006

cis-9, trans-11 conjugated linoleic acid is synthesized directly from vaccenic acid in lactating dairy cattle.

The utilization of (13)C-labeled vaccenic acid (VA) by lactating dairy cows to synthesize cis-9, trans-11 conjugated linoleic acid (CLA) was investigated. Primiparous ruminally cannulated Holstein cows (n = 3) were abomasally infused with 1.5 g of VA-1-(13)C. Blood and milk samples were taken frequently before and after VA infusion. Milk and plasma lipid were extracted using chloroform:methanol. Plasma lipid was separated into triacylglycerol (TG), cholesterol ester (CE), phospholipid (PL), nonesterified fatty acid (NEFA), and mono- and diacylglycerol (MDG) fractions. Lipid was methylated, converted to dimethyl disulfide and Diels-Alder adducts, and analyzed by GC-MS. Increased enrichment of (13)C was determined using a 2-sample t test for each sample time compared with -24 h, with significance declared at P < 0.05. Enrichment in milk fat VA was detected at 4 (3.0%), 8 (8.3%), 12 (4.1%), 16 (2.2%), and 20 h (0.8%). Enrichment in VA was also detected in plasma TG, NEFA, PL, and MDG. Enrichment in milk fat cis-9, trans-11 CLA, the Delta9-desaturase product of VA, was detected at 4 (2.6%), 8 (6.6%), 12 (3.4%), 16 (1.7%), and 24 h (0.7%). Enrichment was not detected in cis-9, trans-11 CLA for any plasma lipid fraction. Modeling of the data showed the exponential decay in (13)C enrichment over time for both VA and cis-9, trans-11 CLA in milk fat. Conversion of dietary VA to cis-9, trans-11 CLA endogenously was confirmed with the mammary gland being the primary site of Delta9-desaturase activity; approximately 80% of milk fat cis-9, trans-11 CLA originated from VA.

Animal Feed↗

PubMed2006

Pharmacokinetics of methylprednisolone acetate after intra-articular administration and its effect on endogenous hydrocortisone and cortisone secretion in horses.

OBJECTIVE: To determine the pharmacokinetics of methylprednisolone (MP) and develop a pharmacokinetic-pharmacodynamic model of the related changes in plasma concentrations of endogenous hydrocortisone (HYD) and cortisone (COR) following intra-articular administration of methylprednisolone acetate (MPA) in horses. ANIMALS: 6 Thoroughbreds. PROCEDURES: In each horse, 200 mg of MPA was injected intrasynovially into a carpal joint, and plasma MP, HYD, and COR concentrations were determined via liquid chromatography-mass spectrometry. RESULTS: A 5-compartment pharmacokinetic-pharmacodynamic model was used to describe the concatenated changes in the plasma concentrations of MP, HYD, and COR and to estimate the instantaneous rate of endogenous HYD production. The median transfer half-life (t(1/2t)) of methylprednisolone from the joint to plasma and elimination half-life (t(1/2e)) from plasma were 1.7 and 19.2 hours, respectively. Maximum plasma concentration of methylprednisolone was 7.26 +/- 3.3 ng/mL at 8 hours, which decreased to 0.11 +/- 0.08 ng/mL at 144 hours after injection. At 3 hours after MPA administration, plasma COR and HYD concentrations were significantly decreased from baseline values (from 2.9 +/- 0.28 ng/mL to 2.10 +/- 1.0 ng/mL and from 61.1 +/- 18.9 ng/mL to 25.7 +/- 12.1 ng/mL, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: The sensitivity of the analytic method used allowed complete description of the related kinetics of MP, HYD, and COR following intra-articular administration of MPA. A single intra-articular administration of MPA profoundly affected the secretion of HYD and COR in horses; secretion of endogenous corticosteroids remained suppressed for as long as 240 hours after injection.

Animals↗

PubMed2005

Estimation of the content of fat and parenchyma in breast tissue using MRI T1 histograms and phantoms.

Mammographic breast density has been correlated with breast cancer risk. Estimation of the volumetric composition of breast tissue using three-dimensional MRI has been proposed, but accuracy depends upon the estimation methods employed. The use of segmentation based on T1 relaxation rates allows quantitative estimates of fat and parenchyma volume, but is limited by partial volume effects. An investigation employing phantom breast tissue composed of various combinations of chicken breast (to represent parenchyma) and cooking fats was carried out to elucidate the factors that influence MRI T1 histograms. Using the phantoms, T1 histograms and their known fat and parenchyma composition, a logistic distribution function was derived to describe the apportioning of the T1 histogram to fat and parenchyma. This function and T1 histograms were then used to predict the fat and parenchyma content of breasts from 14 women. Using this method, the composition of the breast tissue in the study population was as follows: fat 69.9+/-22.9% and parenchyma 30.1+/-22.9%.

Adipose Tissue↗

PubMed2005

AKA-Glucose: a program for kinetic and epidemiological analysis of frequently sampled intravenous glucose tolerance test data using database technology.

BACKGROUND: The Bergman Minimal Model enables estimation of two key indices of glucose/ insulin dynamics: glucose effectiveness and insulin sensitivity. METHODS AND RESULTS: In this paper we describe AKA-Glucose, a program that combines MINMOD Millennium (minimal model analysis software) with relational database technologies. AKA-Glucose enables the fitting of individual frequently sampled intravenous glucose tolerance test (FSIGT) data sets to the Minimal Model and the secure storage in a dedicated database (and retrieval from) of thousands of individual subjects' demographic data, their individual FSIGT data, and each subject's parameters and indices derived from minimal model analysis. AKA-Glucose also enables the population analysis of various strata or subpopulations within the database. AKA-Glucose has all of the capabilities of MINMOD Millennium, provides Minimal Model parameter estimates that are concordant with estimates from previous MINMOD software, and allows importation of data files from earlier versions of the MINMOD software. CONCLUSIONS: By combining FSIGT data fitting, population analysis, and relational database technologies, AKA-Glucose is the first minimal model software designed specifically for researchers confronted with minimal model and epidemiological analysis of large numbers of either human or animal FSIGT data sets.

Adult↗

PubMed2005

The pharmacokinetics of hemoglobin-based oxygen carrier hemoglobin glutamer-200 bovine in the horse.

Hemoglobin-glutamer-200 (HBOC-200) is a hemoglobin (Hb)-based oxygen carrier (HBOC) comprising glutaraldehyde-polymerized bovine Hb. In this study, we sought to determine the pharmacokinetics of this first generation HBOC after IV infusion of 32.5 g of HBOC-200 solution in horses. Quantification of HBOC-200 in equine plasma and urine was performed using a method recently developed by our laboratory. The elimination from plasma was based on size distribution of the bovine Hb polymer. The decline of plasma concentration-time curve of HBOC-200 was described by a noninterchanging 2-compartmental model. The median elimination half-lives of the small and large aggregates were 1.3 and 12.0 h, respectively. Of the HBOC-200 infused, 47.0% was eliminated as the smaller molecular weight and 53% as the larger molecular weight polymers. The area under the plasma concentration-time curve was 5143.1 microg.h(-1).mL(-1). The volumes of distribution of the small and large aggregates were 86.9 and 63.9 mL/kg and the clearances were 42.1 and 3.8 mL.kg(-1).h(-1), respectively. In conclusion, elimination of first generation HBOCs was shown to be more complex than previously assumed because of the heterogeneous nature of these solutions. Mammalian species dispose of Hb using similar mechanisms, and there is no unique metabolic process in the horse that would not allow a logical extension of the general interpretation of this study.

Algorithms↗

PubMed2004

A modified logistic model to describe gadolinium kinetics in breast tumors.

A five-parameter modified logistic equation is presented that describes the signal enhancement in magnetic resonance dynamic contrast enhanced imaging (MRI-DCE). In this heuristic model, P(1) approximates the baseline signal, P(2) is related to the magnitude of the peak signal enhancement, P(3) is the approximate time of the maximum rate of increase of signal, P(4) is related to the maximum rate of signal enhancement, and P(5) is the terminal slope of the signal enhancement curve. Six breast tumors were studied that exhibited diverse patterns of signal enhancement, and in each case, estimated model parameters were well identified. Three of the model parameters, P(2), P(4) and P(5) describe attributes of the signal enhancement curve that have previously been shown to have diagnostic value with respect to breast cancer. Procedures for using the primary model parameters to derive a number of secondary parameters that may also have diagnostic value are discussed. Sensitivity analysis shows that the signal enhancement curve is highly sensitive to P(3) in the region of the signal intensity curve associated with rapid uptake of the contrast reagent. Consequently, frequent signal sampling in this time domain is indicated to enable identification of P(3) and sensitive fitting of the signal intensity curve. The advantages of this heuristic model compared to commonly used compartmental modeling approaches are discussed.

Breast Neoplasms↗

PubMed2004

The rate of de novo galactose synthesis in patients with galactose-1-phosphate uridyltransferase deficiency.

Using both a continuous infusion of isotopically labeled [1-13C]galactose with a steady-state analysis and a single injection kinetic approach, we have calculated the apparent galactose appearance rate (GAR) in patients with galactose-1-phosphate uridyltransferase deficiency and control subjects. With the steady-state protocol, the GAR in 18 patients less than 18 years of age was 1.34+/-0.53 mg/kg/h (mean+/-SD) and was significantly greater than the mean of 0.56+/-0.01 mg/kg/h (p=0.004) in five patients above 18 years of age. Patients who were given a priming dose of [1-13C]galactose had a reduced GAR compared to those without a priming dose, 0.73+/-0.05 (n=9) vs 1.46+/-0.62 (n=14)mg/kg/h (p=0.005). The GAR in controls was lower than in patients ranging from 0.58 to 0.68 mg/kg/h in children and 0.07-0.09 mg/kg/h in adults. In the single bolus studies the plasma [13C]galactose enrichment decreased in a biexponential pattern suggesting at least a two-compartment system. The calculated GAR in three adult patients was similar to that found in them by the continuous infusion technique. The GAR in patients suggests the source of galactose for the continued elevation of galactose metabolites as well as the basis for the long-term complications in galactosemia despite restricted dietary galactose intake.

Adolescent↗

PubMed2003

WinSAAM: a windows-based compartmental modeling system.

Over the last 50 years, complex, dynamic, compartmental models have been used to describe and to make predictions on a host of pharmacokinetic, metabolic, and biological systems. Sophisticated modeling software is required to fit data to such models and to make predictions using these compartmental models. WinSAAM is one such modeling program. The purpose the current report is to describe the features of WinSAAM that make this program suited for modeling all manner of biological systems. We highlight new features, especially those that are unique to WinSAAM, and illustrate with examples how WinSAAM is used to construct models of metabolic systems, to simulate the effects of experiments on systems, and to fit models to data.

Blood Glucose↗

PubMed2003

MINMOD Millennium: a computer program to calculate glucose effectiveness and insulin sensitivity from the frequently sampled intravenous glucose tolerance test.

The Bergman Minimal Model enables estimation of two key indices of glucose/insulin dynamics: glucose effectiveness and insulin sensitivity. In this paper we describe MINMOD Millennium, the latest Windows-based version of minimal model software. Extensive beta testing of MINMOD Millennium has shown that it is user-friendly, fully automatic, fast, accurate, reproducible, repeatable, and highly concordant with past versions of MINMOD. It has a simple interface, a comprehensive help system, an input file editor, a file converter, an intelligent processing kernel, and a file exporter. It provides publication-quality charts of glucose and insulin and a table of all minimal model parameters and their error estimates. In contrast to earlier versions of MINMOD and some other minimal model programs, Millennium provides identified estimates of insulin sensitivity and glucose effectiveness for almost every subject.

Blood Glucose↗