Biomedical subjects

R G Pratt

Publications and source records attributed to R G Pratt.

At least 19 recordsLinked to original sources

PubMed1997

Application of a 3D volume 19F MR imaging protocol for mapping oxygen tension (pO2) in perfluorocarbons at low field.

A limited flip angle gradient-echo 3D volume acquisition imaging protocol for mapping partial pressure of oxygen (pO2) in perfluorocarbon compounds (PFCs) at low field (0.14 T) is presented. The PO2 measurement method is based on the paramagnetic effect of dissolved molecular oxygen (O2) which reduces the PFC 19F T1. Specific objectives related to imaging of PFCs through use of the protocol include improved image signal-to-noise characteristics and elimination of 19F chemical shift artifacts. A parametric Wiener deconvolution filtering algorithm is used for suppression of 19F chemical shift artifacts. Application of the protocol is illustrated in a series of calculated PO2 maps of a gas equilibrated, multi-chamber phantom containing perfluorotributylamine (FC-43). The utility of the protocol is demonstrated in vivo through images of a commercially available perfluorocarbon based blood substitute emulsion containing FC-43 sequestered in the liver and spleen of a rat.

Algorithms↗

PubMed1997

Perfluorocarbon compound aerosols for delivery to the lung as potential 19F magnetic resonance reporters of regional pulmonary pO2.

RATIONALE AND OBJECTIVES: Perfluorocarbon (PFC) aerosols present the opportunity for simultaneous analysis of lung structure and pulmonary oxygenation patterns. The authors investigated techniques to nebulize neat liquid PFCs for inhalation as a new method of PFC administration and tested the hypothesis that PFC aerosols may be developed for efficient delivery to the lung in an experimental rat model allowing the potential for sequential monitoring of pulmonary status via quantitative fluorine-19 (19F) magnetic resonance (MR) partial pressure of oxygen (pO2) imaging. METHODS: Pneumatic aerosol generators were configured to produce a neat liquid PFC perfluorotributylamine (FC-43) aerosol. Perfluorocarbon inhalation breathing protocols for the rat model included: spontaneous direct breathing from an aerosol chamber, and use of a tracheotomy tube to bypass nasal breathing. The PFC aerosol delivery into the rat lung was documented through 19F MR imaging in correlation with high-resolution anatomic proton MR images. Theoretical model calculations for PFC mass deposition were compared with experimental results. RESULTS: The pneumatic generator produced a PFC aerosol droplet within the theoretically targeted range (geometric mean particle diameter of 1.2 microns; concentration of approximately 4 x 10(7) droplets per cm3). No measurable aerosol reached the lungs during spontaneous breathing because of the efficient filtering capabilities of the turbinated nasal passages. With tracheotomy, aerosol depositions within the lung were achieved in mass quantities consistent with theoretical expectations; however, the distribution patterns were nonuniform and unpredictable. Oxygen-enhanced 19F imaging was demonstrated. CONCLUSIONS: Perfluorocarbon aerosols of controlled size distribution can be produced at sufficient concentration with pneumatic generators for distribution to the terminal pulmonary architecture and visualization using 19F MR imaging. The potential exists for in vivo oxygen-sensitive imaging in the pulmonary system and development of sophisticated experimental animal models of systemic oxygen transport as a function of pulmonary status.

Administration, Inhalation↗

PubMed1996

In vivo PO2 imaging in the porcine model with perfluorocarbon F-19 NMR at low field.

Quantitative pO2 imaging in vivo has been evaluated utilizing F-19 NMR in the porcine model at 0.14 T for the lungs, liver, and spleen following i.p. administration of the commercial perfluorotributylamine (FC-43)-based perfluorocarbon (PFC) emulsion, Oxypherol-ET. Calculated T1 maps obtained from a two spin-echo saturation recovery/inversion recovery (SR/IR) pulse protocol are converted into quantitative pO2 images through a temperature-dependent calibration curve relating longitudinal relaxation rate (1/T1) to pO2. The uncertainty in pO2 for a T1 measurement error of +/- 5% as encountered in establishing the calibration curves ranges from +/- 10 torr (+/- 40%) at 25 torr to +/- 16 torr (+/- 11%) at 150 torr for FC-43 (37 degrees C). However, additional uncertainties in T1 dependent upon the signal-to-noise ratio may be introduced through the SR/IR calculated T1 pulse protocol, which might severely degrade the pO2 accuracy. Correlation of the organ image calculated pO2 with directly measured pO2 in airway or blood pools in six pigs indicate that the PFC resident in lung is in near equilibrium with arterialized blood and not with airway pO2, suggesting a location distal to the alveolar epithelium. For the liver, the strongest correlation implying equilibrium was evident for venous blood (hepatic vein). For the spleen, arterial blood pO2 (aorta) was an unreliable predictor of pO2 for PFC resident in splenic tissue. The results have demonstrated the utility and defined the limiting aspects quantitative pO2 imaging in vivo using F-19 MRI of sequestered PFC materials.

Animals↗

PubMed1994

Implementation of a modified birdcage resonator for 19F/1H MRI at low fields (0.14 T).

Fluorine-19 nuclear magnetic resonance of perfluorinated blood substitute materials provides a method for determination of oxygen tension (pO2) in vivo. Use of a double resonant 19F/1H radio frequency coil allows convenient correlation between the high resolution anatomic presentation of proton images and the fluorine distribution. However, quantitative 19F measurements require an RF coil with good H1 field homogeneity over the image volume and a high quality factor (Q) to minimize errors caused by the low signal-to-noise levels available in in vivo imaging and image nonuniformities introduced by the large chemical shift of fluorocarbons. The birdcage coil design provides a high Q structure with optimum H1 field uniformity and fill factor. However, at low resonance frequencies, the inherently low inductance of the birdcage geometry requires the use of a large number of chip capacitors giving rise to unwieldy coil fabrication and increased cost. This communication describes a modification to the birdcage design that reduces the chip capacitor requirement by at least a factor of 4 for a given dimension, yet retains the essential characteristics of the birdcage design. The modified structure was tuned for double resonance at 5.7/6.0 MHz for 19F/1H magnetic resonance imaging at 0.14 T. For a coil with a length to diameter ratio of 1.67, an H1 uniformity of +/- 2% for the 19F resonance was obtained over a cylindrical region with radius approximately 0.6r (r = radius of coil) and length approximately 1.8r within the coil.

Animals↗

PubMed1994

Quantitative pO2 imaging in vivo with perfluorocarbon F-19 NMR: tracking oxygen from the airway through the blood to organ tissues.

The physiological redistribution of perfluorocarbon (PFC) compounds to liver, spleen, bone marrow, and lung after intravenous (i.v.) or intraperitoneal (IP) administration of PFC emulsions affords the unique opportunity for non-invasive monitoring of oxygenation status of these organs and tissues utilizing fluorine (F-19) nuclear magnetic resonance (NMR) imaging techniques. PFCs also may be introduced directly into the pulmonary airways by procedures such as liquid ventilation, intratracheal instillation, or aerosol inhalation. Considerations of importance when establishing methodology for accurate quantitation of oxygen partial pressure (pO2) in vivo using F-19 NMR include: 1.) error analysis of the calibration curves which relate pO2 to the measured PFC F-19 relaxation rate, 2.) optimization of the NMR pulse sequence for efficient oxygen sensitive data acquisition and, 3.) fluorine signal independence from emulsion aqueous phase bioconstituents. The porcine model was investigated at 0.14T following i.v. or IP administration of the PFC emulsion containing perfluorotributylamine (FC-43) to demonstrate the capability for tracking oxygen with F-19 NMR from the lung through the blood to selected organ tissues. Quantitative pO2 projection images and isobaric contour graphs were derived for the liver, spleen, and lungs as a function of inspired oxygen. Blood pO2 levels in aorta, pulmonary artery, and hepatic vein were monitored simultaneously with NMR imaging for correlative analysis.

Animals↗

PubMed1992

Magnetic resonance imaging of neural transplants in rat brain using a superparamagnetic contrast agent.

Rat fetal brain tissue was incubated in vitro with superparamagnetic ferrite particles covalently coupled to the lectin wheat germ agglutinin (WGA) and transplanted into the adult rat striatum. At 6 days and at 3 weeks post-surgery the transplants were observed on T1 weighted magnetic resonance (MR) images of the rat head as an area of relatively low signal intensity which could be clearly differentiated from the higher signal intensity produced by the host brain. Histological analysis revealed that the ferrite particles were largely restricted to the transplant in a patchy distribution. The ferrite particles were associated with cells having an apparent normal morphology. Superparamagnetic ferrite particles act as potent MR contrast agents and can be used to label transplanted cells. The labeled cells are apparently not adversely affected by the WGA-ferrite particles and can be monitored for at least three weeks in vivo using noninvasive MR imaging.

Animals↗

PubMed1992

Quantitation of perfluorocarbon blood substitutes in tissues using F-19 magnetic resonance spectroscopy.

F-19 Magnetic Resonance Spectroscopy (MRS) has been used to quantitate the biodistribution of perfluorocarbon (PFC) blood substitutes in porcine tissues following intraperitoneal administration of a 20% w/v perfluorotributylamine (FC-43) based emulsion. PFC tissue concentrations were determined for spleen, liver and lung tissues from juvenile pigs ranging in weight from 12 to 15 kg. Typical average values (mmoles FC-43/gram tissue) ranged from 0.23-0.39 for spleen; 0.09-0.13 for liver; and 0.09-0.12 for lung. A description of this spectroscopy based quantitation technique will be presented. F-19 MRS is a specific, rapid, and accurate method for measurement of PFC tissue concentrations.

Animals↗

PubMed1991

Magnetic resonance imaging of rat brain following in vivo disruption of the cerebral vasculature.

Intravenous administration of hyperosmotic mannitol into rats produced a disruption of the blood-brain barrier (BBB). This was visualized by T1 weighted magnetic resonance (MR) imaging following intravenous administration of the MR contrast agent gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). Following administration of the Gd-DTPA there was an increase in signal intensity corresponding to the cerebral cortex. There was also an increase in signal intensity in features corresponding to the lateral ventricles. However, there was no increase in signal intensity within the striatum indicating that the vasculature within the striatum was resistant to disruption by the hyperosmotic mannitol. The tumors formed by C-6 glioma cells were isointense with rat brain on precontrast MR images. Following intravenous administration of Gd-DTPA, in a representative rat, the tumor was visualized as areas of high signal intensity. There was no enhancement of normal brain by Gd-DTPA. Thus, the tumor had different vascular properties than the host brain with respect to permeability of the contrast agent. Furthermore, Gd-DTPA did not enter the normal brain via the tumor. Thirty days following unilateral injection of kainic acid (KA: 5 nmol) into rat striatum, the shrinkage of the lesioned striatum and the concomitant enlargement of the lateral ventricles was visible on the precontrast MR images. Following administration of Gd-DTPA, there was no enhancement of any regions of the brain. Therefore, the structural perturbations of the striatum produced by KA lesions were not accompanied by disruption of the BBB. These studies demonstrate that MR imaging represents a useful technique for investigating in vivo the perturbation of the cerebral vasculature in rat models of neuropathologies.

Animals↗

PubMed1991

Software and hardware integration of a microprogrammable state machine for NMR imaging.

We have integrated a commercially available microprogrammable state machine (Tecmag PULSkit) for use as a magnetic resonance pulse programmer. Providing the capability for active research environment imaging protocols, it features timing resolution of 100 nsec, ten 16-bit loop counters, and individually addressable look-up tables. This integration involved hardware and software integration with a VAX 11/750 at several levels. Hardware: Each of the three gradient channels employs three digital-to-analog converters (DACs). An 8-bit, 4-quadrant, multiplying DAC generates the gradient waveform shape. A 12-bit DAC generates the multiplying DAC scaling voltage, controlling gradient amplitude and sign. A third 12-bit DAC produces a gradient offset (shim) voltage. An eddy current compensation network is present for each gradient channel. Software: The software design philosophy was to create a flexible interface (interactive window environment), while not constraining complex manipulation of the hardware (direct use of the pulse-sequence compiler primitives and microprogramming). The software levels include (a) pulse-sequence microprogramming, (b) pulse-sequence compiler, (c) interactive parameter specification, and (d) canned pulse-sequence microcode library.

Computer Systems↗

PubMed1990

T1 and T2 weighted magnetic resonance imaging of excitotoxin lesions and neural transplants in rat brain in vivo.

On T1- and T2-weighted magnetic resonance (MR) images obtained at 0.14 T the rat brain was visible in the rat head as an area of relative high signal intensity. The enlarged lateral ventricles produced by intrastriatal injections of the excitotoxin kainic acid (KA) were clearly visible as areas of low signal intensity in T1-weighted images but could not be differentiated from normal brain tissue on T2-weighted images for the protocols utilized. Repeated T1-weighted MR images of individual rats demonstrated a progression in the extent of the lesions over an approximately 14-week period following the injection of KA. On the T2-weighted images, areas of relatively high signal intensity corresponding to tissue on the lesioned side of the brain were evident. As the lesion progressed and the remaining tissue visible on the T1-weighted images decreased, the region of high signal intensity visible on the T2-weighted images diminished. This area of high signal intensity on the T2-weighted images appeared to correspond to tissue undergoing a neurodegenerative process. MR images from contiguous slices of brain demonstrated the extent of the KA-induced degeneration throughout the brain, although volume averaging of multiple brain structures was a possible confounding factor. Features apparently corresponding to fetal striatal tissue transplants growing within the enlarged lateral ventricle were visible on T1-weighted images but could not be discriminated on the T2-weighted images. MR imaging is useful for monitoring in vivo the anatomical location and progression of excitotoxin lesions and the location of fetal striatal tissue transplants in lesioned rat brain.

Animals↗

PubMed1989

A magnetic resonance imaging contrast agent differentiates between the vascular properties of fetal striatal tissue transplants and gliomas in rat brain in vivo.

The tumors formed by rat C-6 glioma cells were isointense with the normal rat brain on precontrast T1 weighted magnetic resonance (MR) images. Following i.v. peripheral administration of the MR imaging contrast agent gadolinium (Gd)-DTPA, there was no significant change in the signal intensity from normal brain tissue. However, the tumor appeared as areas of high signal intensity demonstrating the abnormal vascular properties of the tumor. Fetal rat striatal tissue transplanted into unlesioned adult rat striatum appeared isointense with the host brain on precontrast T1 weighted images and there was no evidence for enhancement of the transplanted tissue relative to host brain following i.v. administration of Gd-DTPA. Using this technique we found no evidence with respect to permeability of the contrast agent of an abnormal blood-brain barrier within the striatal transplant in vivo.

Animals↗

PubMed1989

Magnetic resonance imaging of rat brain following kainic acid-induced lesions and fetal striatal tissue transplants.

Use of a small diameter (5.1 cm) radiofrequency coil provided relatively high resolution magnetic resonance (MR) images of rat heads at 0.14 Tesla. On T1-weighted images, the rat brain was clearly visible in the rat head as a region of high signal intensity. No structures were distinguished within the normal rat brain. In contrast, in the brains of rats receiving unilateral kainic acid lesions of the striatum, enlarged lateral ventricles, which are characteristic of the lesion, were clearly visible as dark areas of low signal intensity. Extrastriatal damage on the lesioned side of the brain was also evident in some of the images. Fetal striatal tissue transplants growing within the lesioned striata were also identified in the MR images. The transplanted tissue appeared as areas of high and intermediate signal intensity, similar to the host brain. MR imaging is a useful technique for monitoring excitotoxin lesions of brain and fetal striatal tissue transplants in vivo.

Animals↗

PubMed1987

Magnetic resonance imaging of congenital hydrocephalus in the rat.

Magnetic resonance imaging (MRI) is an increasingly available technique in clinical medicine for the noninvasive imaging of soft tissues. The purpose of the present study was to demonstrate the potential utility of MRI in experimental toxicology and teratology studies. The progression of severity of prenatally induced hydrocephalus was observed in rat pups from 1 to 4 weeks of age. Pregnant Sprague-Dawley rats were given 0, 15, 30, or 45 mg/kg ethylenethiourea (ETU), po, on Gestation Day 15. The two higher doses have been reported to induce a high incidence of hydrocephalus, which is mild at birth but becomes extensive by 4 weeks of age. The low dose was a no effect level for hydrocephalus. None of the doses of ETU altered birth weight or litter size. Pups from each dose group were imaged serially, on Postnatal Days (PD) 6, 13, 17, and 27, in order to determine the progression in the severity of hydrocephalus. Littermates were also imaged on each of these days, then killed immediately in order to compare the anatomy of the brain with its MR image. Hydrocephalus was detectable in the images from all animals of the 30 and 45 mg/kg dose groups on PD 6, the earliest observation day. At this time, the lateral ventricles were dilated less than 1 mm. Hydrocephalus became increasingly severe, and by 4 weeks of age all of the 45 mg/kg group and approximately half of the 30 mg/kg group had died. The brains of the surviving 30 mg/kg rats were severely hydrocephalic, with little cortex remaining. In all cases, the MR image corresponded precisely with the brain anatomy observed after termination. We have demonstrated that MRI is a useful technique for noninvasively imaging lesions in experimental animals. A number of other potential uses for MRI in toxicology are presented.

Animals↗

PubMed1984

Perfluorinated organic liquids and emulsions as biocompatible NMR imaging agents for 19F and dissolved oxygen.

Emulsions of fluorocarbons are finding considerable use in physiology for intravascular oxygen transport. Their wide clinical application as blood substitutes, anti-shock, and anti-ischemic agents seems imminent. Whole body NMR imaging is rapidly gaining clinical application and may one day almost completely supplant X-ray imaging. All of the 19F compounds used in biocompatible fluorocarbon emulsions give 19F signals identical to those in the corresponding neat liquid. In concentrations of 10% w/v they are readily imaged. The paramagnetic oxygen molecule reduces T1 in such a way as to make possible whole body imaging of oxygen. T1 typically decreases from 1-4 to 0.3-0.5 seconds and is an inverse linear function of oxygen tension. Spin-lattice relaxation times versus oxygen tensions from 0 to 600 torr have been obtained for F-decalin, F-tributylamine, and F-44E. The usefulness of these 19F effects in clinical NMR imaging depends upon the sensitivity of the method and the tolerable dose. The 19F signal may find use in monitoring 19F compounds as vapors or gases dissolved in plasma or in perfluorocarbons in neat liquid or particle form.

Animals↗

PubMedDate not supplied

Evaluation of the influence of the aqueous phase bioconstituent environment on the F-19 T1 of perfluorocarbon blood substitute emulsions.

Oxygen-sensitive F-19 magnetic resonance imaging of perfluorocarbon compounds requires that fluorocarbon T1 changes correlate with the local PO2 and not with the composition of the surrounding aqueous phase. The influence of various bioconstituents and paramagnetic ions within the aqueous phase on the F-19 fluorocarbon phase T1 for PFC emulsions was evaluated at 0.14 and 0.66 T. T1 was measured for FC-43, perflubron, and a fluorinated surfactant. Controlled variables introduced in the aqueous phase included annex solution constituents, blood, pH changes, and Gd-DTPA. For a constant PO2, the F-19 T1s were independent of the emulsion constituents, blood concentration, and pH. For FC-43 and perflubron, F-19 T1 was independent of the Gd-DTPA concentration, while the aqueous phase T1 decreased by more than an order of magnitude. XMO-10 (smallest emulsion particle size) showed a slight decrease in F-19 T1 with increasing Gd-DTPA concentration at 0.66 T.

Animals↗

PubMedDate not supplied

Intravascular irradiation using Re-186 liquid-filled balloon catheters: correlation between experimental and theoretical studies.

PURPOSE: Optimization of intravascular radiation to reduce stenosis following coronary angioplasty requires the ability to predict the patterns of radiation dose distribution. This investigation evaluated the agreement between Monte Carlo simulations and experimental radiation dose measurements for a radioisotope liquid-filled balloon catheter in a tissue equivalent phantom. METHODS AND MATERIALS: Direct measurements of the radiation dose from Re-186 liquid-filled balloons were made using thermoluminescent dosimeters (TLDs) and radiochromic film. Monte Carlo simulations were carried out using the Monte Carlo N-Particle code system (MCNP4B). RESULTS: The Monte Carlo generated dose values agreed with the experimentally determined results within the statistical uncertainty. A slightly higher penetration was indicated by regression analysis for the TLD data relative to the MCNP4B prediction that may be due to experimental configuration anomalies. For this balloon catheter, approximately 55 mCi of Re-186 will deliver 15 Gy at a 0.5 mm depth in tissue equivalent material in 5 min. CONCLUSIONS: Correlation between experimentally measured dose values and Monte Carlo computation supports the position that MCNP4B simulations constitute a valuable tool for investigating various clinical therapy designs. The agreement between Monte Carlo calculations and experiments provide confidence in applying MCNP4B to more sophisticated geometries of interest, and other methods of intravascular radiation dose delivery.

Angioplasty, Balloon, Coronary↗

PubMedDate not supplied

MR imaging of the lung using liquid perfluorocarbons.

Certain perfluorocarbon (PFC) compounds, commonly used as the oxygen transport components of "blood substitutes," may be breathed as neat liquids with survival because of their chemical inertness and their high solubility for oxygen and carbon dioxide. In addition, the paramagnetism of oxygen reduces the fluorine T1 value according to an inverse relationship allowing a potential method of monitoring PO2 gradients in vivo. This article presents the results of magnetic resonance (MR) imaging of the lungs of mice and rats following breathing of four PFC liquids (FC-43, FC-75, PFOB, APF-215). The images presented were obtained at two magnetic field strengths (0.66 and 0.14 T) under conditions of breathing either ambient air or pure oxygen. Spin-lattice relaxation times (T1) for the PFCs are measured both in vitro and in vivo (in the lungs) as a function of the state of oxygenation. A MR image signal strength enhancement of up to 90% is demonstrated in vivo under conditions of pure oxygen breathing.

Animals↗

PubMedDate not supplied

Deconvolution of chemical shift spectra in two- or three-dimensional [19F] MR imaging.

The chemical shift spectra of 19F in perfluorinated compounds (PFCs) present a nontrivial impulse response function for magnetic resonance (MR) imaging. The 19F images of organs containing PFCs can be degraded by blurring and ghost image artifacts. Two methods (noise masked deconvolution and maximum entropy deconvolution) are presented that allow the chemical shift spectra of 19F in PFCs to be used to extract high quality MR images free of chemical shift artifact. Both techniques rely on postprocessing of either the raw data or the original image to produce images that are not degraded by the chemical shift spectra of the compound being imaged and that exhibit a signal-to-noise ratio equal to or better than that observed in the original image. The techniques are general in that they can be used with many PFC spectra. Using MR imaging data obtained from phantoms filled with cis/transperfluorodecalin and perfluorotributylamine (FC-43), the methods are compared in terms of their (a) ability to eliminate the chemical shift artifact associated with the PFC spectrum; (b) signal-to-noise performance; and (c) ability to preserve information related to the density and the longitudinal relaxation rate of the resonant nuclei. The utility of these techniques is demonstrated by a series of three-dimensional Fourier transform in vivo images of FC-43 emulsion in a mouse liver.

Algorithms↗