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Biomedical subjects

S R Thomas

Publications and source records attributed to S R Thomas.

156 records · Page 9Linked to original sources

Biokinetics and dosimetry analysis in healthy volunteers for a two-injection (rest-stress) protocol of the myocardial perfusion imaging agent technetium 99m-labeled Q3.

BACKGROUND: Trans (N,N'-ethylene bis(acetylacetoneimine)) bis(tris(3-methoxy-1-propyl) phosphine) 99mTc(III) (99mTc-Q3) has been developed for myocardial perfusion imaging. Biokinetic studies and dosimetry analysis have been completed for six healthy volunteers. METHODS AND RESULTS: The same-day two-injection protocol involved (1) an average rest injection of 241 MBq of 99mTc-Q3 followed by myocardial single-photon emission computed tomography (SPECT) at 15.0 minutes and a whole body (WB) scan at 1.5 hours; and (2) an average stress injection during treadmill exercise of 744 MBq of 99mTc-Q3 at 2.4 hours (postrest injection) followed by myocardial SPECT and additional WB scans at 1.5, 3.5, 6.5, and 21 hours poststress injection. Total urine was collected over 24 hours. Absolute organ activities were determined by conjugate counting methods. The two-injection data were simplified to a one-injection equivalent data set to facilitate dosimetry analysis. Decay corrected average percentage uptake values, plus or minus one standard deviation, for the myocardium were 1.4% +/- 0.2% at approximately 1.5 hours for both the postrest and poststress injections. The average biologic half-time for the myocardium was 26.4 hours. The highest organ uptake values included the gallbladder with 5.5% +/- 1.9% and the liver with 4.1% +/- 1.0% at the 1.5 hours poststress scan time. The sum of all gastrointestinal (GI) tract components was 18.8% +/- 9.4% at approximately 6.5 hours poststress injection (before any fecal elimination). The total 24 hour urine clearance was 17.1% +/- 2.4%. The gallbladder wall and upper large intestine wall received the highest doses at 0.024 and 0.023 mGy/MBq, respectively. CONCLUSION: The effective dose equivalent is estimated to be 0.01 mSv/MBq, which for an administration of 1110 MBq (30 mCi) is less than half that of a standard imaging protocol using 111 MBq (3 mCi) of 201Tl, and comparable to the published estimates for 99mTc-labeled sestamibi and 99mTc-labeled tetrofosmin (also normalized to 1110 MBq of administered activity). The 99mTc-Q3 exhibits myocardium uptake similar to that for these other two 99mTc agents.

Adult↗

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↗

Cloning and expression of Trichoderma reesei cellobiohydrolase I in Pichia pastoris.

Pichia pastoris was transformed with the Trichoderma reesei cbh1 gene, and the recombinant enzyme was purified and analyzed kinetically and by circular dichroism. The P. pastoris rCBH I was recognized by MoAb raised to T. reesei CBH I but was found in multiple molecular weight species on SDS-PAGE gels. Carbohydrate content determination and SDS-PAGE western analysis indicated that the recombinant protein was hyperglycosylated, although a species very similar in molecular weight to the T. reesei enzyme could be isolated chromatographically. The P. pastoris rCBH I also demonstrated activity toward soluble and insoluble substrates (i.e., pNPL and Sigmacell), although at a level significantly lower than the wild-type enzyme. More seriously, the yeast-expressed enzyme showed non-wild-type secondary structure by circular dichroism. We conclude that P. pastoris may not serve as an adequate host for the site-directed mutagenesis of T. reesei CBH I.

Amino Acid Sequence↗

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↗

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↗

In vivo quantitation of lesion radioactivity using external counting methods.

Quantitative external counting methods for the in vivo determination of the activity uniformly distributed in an area of interest (lesion) have been developed. The theoretical work has been extended to include the effects of regions of differing attenuation coefficient and of non-target organ activity in the tissue surrounding the lesion. A clinical quantitative procedure utilizing a "calibrated" gamma camera and associated computer system is described. Studies including a bone substitute material in a water phantom confirmed the basic theoretical work.

Models, Structural↗

An evaluation of the performance characteristics of different types of collimators used with the EMI brain scanner (MKI) and their significance in specific clinical applications.

The characteristics of various types of collimators have been studied systematically for the EMI Mark I brain scanner. The degree of collimation ranged from the 13-mm adjacent A and B slices to 3-mm separated slices. Multiple phantom studies (including variable density immiscible liquid interfaces) have been performed to evaluate the effect of collimation on (a) the line-spread function, (b) the change in effective absorption number, and (c) volume averaging. Effects associated with the technique settings involving the kVp, the mA, and the scan time were also investigated. The results of TLD dose measurements as a function of collimation are presented. The significance of collimation in specific clinical studies involving small, fairly well-circumscribed lesions is discussed.

Brain Diseases↗

Deconvolution techniques for removing the effects of chemical shift in 19F nuclear magnetic resonance imaging of perfluorocarbon compounds.

Nuclear magnetic resonance (NMR) imaging of perfluorocarbon (PFC) emulsions and neat liquids has shown potential for in vivo oxygen imaging in blood and organ tissue. PFC compounds exhibit complicated NMR spectra caused by chemical shifts and spin-spin couplings which can lead to artifacts and degraded spatial resolution of resulting NMR images. To correct for the chemical shift artifacts, the technique of spectral deconvolution has been applied to NMR imaging of PFC compounds. The temporal filter for this process can be directly applied to raw free induction decay data in projection reconstruction or to spin-echo data in two-dimensional Fourier transform imaging techniques. The effect of chemical shift artifacts was demonstrated through the NMR imaging of two PFC compounds (F-tributylamine and F-decalin) in phantoms. Methods are presented and demonstrated which allow the chemical shift artifacts to be removed and true images of the spatial distribution of the PFC's to be recovered.

Blood Substitutes↗

Resonator coils for magnetic resonance imaging at 6 MHz.

The Alderman and Grant design of the slotted tube resonator has been modified with a different lumped capacitor distribution to obviate the need for a balanced electrical feed at low frequencies (6 MHz). A saddle coil resonator and a strip line resonator have been tuned with similar lumped capacitor distributions to obtain electrically balanced resonance.

Brain↗