Biomedical subjects

Stephen Pickup

Publications and source records attributed to Stephen Pickup.

9 recordsLinked to original sources

PubMed2006

Phasic respiratory pharyngeal mechanics by magnetic resonance imaging in lean and obese zucker rats.

RATIONALE: Although obstructive sleep apnea is strongly associated with obesity, we have little understanding of how obesity may alter the mechanical properties of the pharynx and the role of obesity in the pathogenesis of sleep apnea. OBJECTIVES: The overall objective of this study was to determine the effect of obesity on pharyngeal airway size and pharyngeal wall tissue strain in lean and obese Zucker rats. METHODS: Respiratory-gated magnetic resonance imaging with noninvasive tissue tagging was performed in anesthetized, spontaneously breathing lean (n = 9) and obese (n = 9) Zucker rats. Images acquired during expiration and inspiration of the rostral, mid-, and caudal pharynx were analyzed for airway size and pharyngeal wall tissue strain, using planimetry, optical flow, and finite element analyses. Differences in cross-sectional airway area, lateral and anteroposterior airway diameters, and tissue strain (stretch, compression, and direction of stretch) in the lateral and ventral pharyngeal walls were compared by analysis of variance (significance at p < 0.05). MEASUREMENTS AND MAIN RESULTS: Compared with their lean littermates, obese rats had the following significant findings: reduced pharyngeal airway cross-sectional area during inspiration and expiration, smaller increases in airway area during inspiration, and decreased lateral airway dilation during inspiration. Tissue strain in the pharyngeal walls showed no significant differences between obese and lean rats. CONCLUSIONS: These findings suggest that obesity results in a mechanical abnormality that decreases pharyngeal airway size and prevents a normal airway response to a given change in pharyngeal wall tissue strain.

Airway Resistance↗

PubMed2005

Increases in NMR-visible lipid and glycerophosphocholine during phenylbutyrate-induced apoptosis in human prostate cancer cells.

DU145 human prostatic carcinoma cells were treated with the differentiating agents phenylacetate (PA) and phenylbutyrate (PB) and examined in perfused cultures by diffusion-weighted 1H and 31P nuclear magnetic resonance spectroscopy (NMR). PA and PB (10 mM) induced significant (>3-fold) time-dependent increases in the level of NMR-visible lipids and total choline in 1H spectra, and glycerophosphocholine levels in the 31P spectra, with the increases being greater for PB. These effects were accompanied by significant increases in cytoplasmic lipid droplets and intracellular lipid volume fraction as observed by morphometric analysis of Oil Red O-stained cells. PB treatment caused cell cycle arrest in the G1 phase and induction of apoptosis. In contrast, PA-treated DU145 cells showed an accumulation of cells in G2/M and no evidence of apoptosis. These results demonstrate that significant differences exist in the mechanism of PA and PB activity, although both compounds cause similar, but graded alterations in lipid metabolism. The simultaneous accumulation of mobile lipid and glycerophosphocholine suggests that PB and PA induce phospholipid catabolism via a phospholipase-mediated pathway. The mobile lipid accumulation following the induction of either apoptosis and cytostasis by related differentiating agents indicate that the presence of NMR-visible lipids may not be a specific event causally resulting from the induction of apoptosis.

Apoptosis↗

PubMed2005

Gadodiamide T1 relaxivity in brain tissue in vivo is lower than in saline.

In vivo measurements of gadodiamide (Gd-DTPA-BMA) T(1) relaxivity were performed at 4.7 T in injured and normal rat brains. Cerebral lesions were induced in nine rats by a localized freezing method. T(1) maps of the lesions were generated before and after injection of Gd-DTPA-BMA (0.1-0.6 mmol/kg). Samples of normal and necrotic brain were collected postmortem; the wet and dry weights were determined, and Gd content was measured by inductively coupled plasma mass spectroscopy. The in vivo relaxivity was determined by a linear fit of a plot of the change in relaxation rate following injection of the contrast agent as a function of Gd content. This analysis yielded a relaxivity in the injured brain of 2.8 sec(-1) mmol(-1) kg tissue water at 36 degrees C. The water weight fraction was 0.90 +/- SD 0.02 wt/wt in injured brain and 0.79 +/- 0.02 in normal brain. Relaxivity measurements were also performed on solutions of Gd-DTPA-BMA (0.0-0.6 mmol) and albumin (0-30% wt/wt) in normal saline at room and physiologic temperatures. The relaxivity in the albumin/saline increased with increasing solids content with values of 4.0-4.9 sec(-1) mmol(-1)kg at 21 degrees C and 3.4-4.5 sec(-1) mmol(-1) kg at 37 degrees C. The relaxivity of the tissues differed significantly from that of the saline solutions of comparable solids content, suggesting that the solids content of a tissue is not the only factor that determines in vivo relaxivity.

Animals↗

PubMed2005

Artificial tumor model suitable for monitoring 31P and 13C NMR spectroscopic changes during chemotherapy-induced apoptosis in human glioma cells.

An artificial tumor method was developed to study cells inside the sensitive volume of an NMR spectrometer during growth and apoptosis. The tumor was composed of a 50:50 mixture of tightly packed porous-collagen and nonporous-polystyrene microspheres. The porous collagen served as a growth surface for the tumor cells, and the nonporous polystyrene served as a structural support to limit compression of the packed bed during perfusion. The microspheres were held between two porous polyethylene discs that were tightly sealed inside the NMR perfusion chamber. The new method was evaluated with two cell types: a mouse mammary tumor line (EMT6/SF) and a human glioma line (SF188). The results indicate that for both lines, approximately 10(9) metabolically active cells could be sustained for at least 1 week in the 12-cm(3) artificial tumor. Further, cells undergoing chemotherapy-induced apoptosis (which is known to cause detachment of cells from their surroundings) were retained in the artificial tumor. In preliminary 31P NMR studies, glioma cells treated with temozolomide (TMZ) exhibited reduced phosphocholine (PCh) levels relative to glycerophosphocholine (GPC) and diphosphodiester (DPDE) levels. They also exhibited sharply reduced oxygen consumption and TCA cycle 13C labeling, while they retained glycolytic activity. These metabolic changes are consistent with those that would be expected during mitochondrially-mediated apoptosis.

Animals↗

PubMed2004

Pharyngeal airway wall mechanics using tagged magnetic resonance imaging during medial hypoglossal nerve stimulation in rats.

To better understand pharyngeal airway mechanics as it relates to the pathogenesis and treatment of obstructive sleep apnoea, we have developed a novel application of magnetic resonance imaging (MRI) with non-invasive tissue tagging to measure pharyngeal wall tissue motion during active dilatation of the airway. Eleven anaesthetized Sprague-Dawley rats were surgically prepared with platinum electrodes for bilateral stimulation of the medial branch of the hypoglossus nerve that supplies motor output to the protrudor and intrinsic tongue muscles. Images of the pharyngeal airway were acquired before and during stimulation using a gated multislice, spoiled gradient recalled (SPGR) imaging protocol in a 4.7 T magnet. The tag pulses, applied before stimulation, created a grid pattern of magnetically imbedded dark lines that revealed tissue motion in images acquired during stimulation. Stimulation significantly increased cross-sectional area, and anteroposterior and lateral dimensions in the oropharyngeal and velopharyngeal airways when results were averaged across the rostral, mid- and caudal pharynx (P < 0.001). Customized software for tissue motion-tracking and finite element-analysis showed that changes in airway size were associated with ventral displacement of tissues in the ventral pharyngeal wall in the rostral, mid- and caudal pharyngeal regions (P < 0.0032) and ventral displacement of the lateral walls in the mid- and caudal regions (P < 0.0001). In addition, principal maximum stretch was significantly increased in the lateral walls (P < 0.023) in a ventral-lateral direction in the mid- and caudal pharyngeal regions and principal maximum compression (perpendicular to stretch) was significantly increased in the ventral walls in all regions (P < 0.0001). Stimulation did not cause lateral displacement of the lateral pharyngeal walls at any level. The results reveal that the increase in pharyngeal airway size resulting from stimulation of the medial branch of the hypoglossal nerve is predominantly due to ventral displacement of the ventral and lateral pharyngeal walls.

Animals↗

PubMed2004

A novel method for analysis of TOMROP data.

PURPOSE: To develop an efficient method for extracting maps of the corrected T1 from images generated using the T One by Multiple Read Out Pulses (TOMROP) sequence. MATERIALS AND METHODS: An expression is developed for the true T1 in terms of the parameters from a three-parameter fit of the TOMROP data. Solutions of gadodiamide in normal saline with concentrations of 0.0, 0.06, 0.11, 0.23, 0.46, and 0.91 mM were prepared and T1 measurements were performed using both the inversion recovery (IR) and the TOMROP methods. The TOMROP data were analyzed using the proposed technique and the results compared to those from the IR measurements. RESULTS: The T1 estimates generated from the TOMROP data using the proposed method were consistent with the IR results. However, systematic errors were observed in the T1 estimates when the repetition time was not sufficient for full recovery of axial magnetization. Relaxation times determined using the proposed method were within 1% of the spectroscopiclly determined values for T1 values in the range of 0.28-2.8 seconds when a suitable delay was employed. CONCLUSION: The proposed method of analysis was found to yield accurate T1 estimates when the assumptions used in the analysis were not violated.

Contrast Media↗

PubMed2004

Simultaneous measurement of arterial input function and tumor pharmacokinetics in mice by dynamic contrast enhanced imaging: effects of transcytolemmal water exchange.

A noninvasive technique for simultaneous measurement of the arterial input function (AIF) for gadodiamide (Omniscan) and its uptake in tumor was demonstrated in mice. Implantation of a tumor at a suitable location enabled its visualization in a cardiac short axis image. Sets of gated, low-resolution saturation recovery images were acquired from each of five tumor-bearing mice following intravenous administration of a bolus of contrast agent (CA). The AIF was extracted from the signal intensity changes in left ventricular blood using literature values of the CA relaxivity and a precontrast T1 map. The time-dependent 1H2O relaxation rate constant (R1 = 1/T1) in the tumor was modeled using the BOLus Enhanced Relaxation Overview (BOLERO) method in two modes regarding the equilibrium transcytolemmal water exchange system: 1) constraining it exclusively to the fast exchange limit (FXL) (the conventional assumption), and 2) allowing its transient departure from FXL and access to the fast exchange regime (FXR), thus designated FXL/FXR. The FXL/FXR analysis yielded better fittings than the FXL-constrained analysis for data from the tumor rims, whereas the results based on the two modes were indistinguishable for data from the tumor cores. For the tumor rims, the values of Ktrans (the rate constant for CA transfer from the vasculature to the interstitium) and ve (volume fraction of the tissue extracellular and extravascular space) returned from FXL/FXR analysis are consistently greater than those from the FXL-constrained analysis by a factor of 1.5 or more corresponding to a CA dose of 0.05 mmole/kg.

Animals↗

PubMed2003

Assessment of global and regional myocardial function in the mouse using cine and tagged MRI.

Mouse models are expected to play an important role in future investigations of human cardiac diseases. In the present report, MRI methods for determining global and regional cardiac function in the mouse are demonstrated. ECG-gated cine images were acquired in five C57BL/6 mice at physiological temperatures (37 degrees C) and heart rates of 500 +/- 50 beats per minute. Left ventricular mass, ejection fraction, and cardiac output were estimated from the resulting images. Regional myocardial function was also determined in three animals by application of 2D SPAtial Modulation of Magnetization (SPAMM) in combination with the cine protocol. The quality of the tagged images was sufficient to allow mapping of myocardial strains and displacements. The results of the regional strain analysis were consistent with similar studies in larger animals. This work demonstrates the first characterization of regional myocardial function in the mouse via SPAMM techniques.

Animals↗

PubMed2003

MRI estimation of the arterial input function in mice.

RATIONAL AND OBJECTIVES: Dynamic contrast-enhanced (DCE) MRI offers the potential to provide quantitative maps of tumor perfusion parameters and is therefore expected to play an important role in the study of cancer in small animal models. Extraction of such information from DCE-MRI data requires a methodology for determination of the arterial input function (AIF) for the target tissues. An MRI based method for observation of the AIF in a mouse model is demonstrated in the present report. MATERIALS AND METHODS: A series of short-axis cardiac images was acquired during the first pass of a bolus of Gadodiamide using a low-resolution, EEG-gated, saturation-recovery gradient echo imaging sequence. The AIF was then extracted from the observed signal intensity changes in the left ventricle (LV) blood pool. RESULTS: The proposed technique provides sufficient temporal and spatial resolution to accurately characterize the AIF of Gadodiamide in mouse models. The AIF was observed in 4 mice and was found to be qualitatively similar to that previously observed in larger animals. However, significant inter-animal variability in the precise form of the AIF was evident. CONCLUSIONS: The proposed method for determination of AIF in mice has been shown to be effective and reliable. The inter-animal variability observed in the present study suggests that the AIF should be measured in each animal undergoing analysis by DCE-MRI.

Animals↗