Biomedical subjects

S R Cherry

Publications and source records attributed to S R Cherry.

At least 55 records · Page 3Linked to original sources

PubMed1997

Oral 18F-fluoro-2-deoxyglucose for primate PET studies without behavioral restraint: demonstration of principle.

We describe a method of orally administering 18F-fluoro-2-deoxyglucose (FDG) for positron emission tomography (PET) scans to determine local cerebral metabolic rates for glucose (LCMRGlc), normalized to that of whole brain, in fully conscious, non-restrained primates. Oral FDG-PET studies were performed in both non-restrained and chaired monkeys, and in one human where results could be compared with traditional intravenous FDG administration. The oral route of FDG administration gave images and whole brain-normalized PET LCMRGlc results comparable to those obtained by the intravenous route. This oral FDG-PET method may provide a useful means by which to obtain measures of LCMRGlcs for brain structures, relative to each other, in non-restrained, non-drugged primates in field and laboratory studies. This method might also have clinical applications for PET studies of children.

Administration, Oral↗

PubMed1997

PET and NMR dual acquisition (PANDA): applications to isolated, perfused rat hearts.

Positron emission tomography and nuclear magnetic resonance spectroscopy are non-invasive techniques that allow serial metabolic measurements to be obtained in a single subject. Significant advantages could be obtained if both types of scans could be acquired with a single machine. A small-scale PET scanner, designed to operate in a high magnetic field, was therefore constructed and inserted into the top half of a 7.3 cm bore, 9.4 T NMR magnet and its performance characterized. The magnetic field did not significantly affect either the sensitivity (approximately 3 kcps/MBq) or the spatial resolution (2.0 mm full width at half maximum, measured using a 0.25 mm diameter line source) of the scanner. However, the presence of the PET scanner resulted in a small decrease in field homogeneity. The first, simultaneous 31P NMR spectra (200, 80 degrees pulses collected at 6 s intervals) and PET images (transverse, mid-ventricular slices at the level of the mitral value) from isolated, perfused rat hearts were acquired using a specially designed NMR probe inserted into the bottom half of the magnet. The PET images were of excellent quality, enabling the left ventricular wall and interventricular septum to be clearly seen. In conclusion, we have demonstrated the simultaneous acquisition of PET and NMR data from perfused rat hearts; we believe that the combination of these two powerful techniques has tremendous potential in both the laboratory and the clinic.

Adenosine Triphosphate↗

PubMed1997

Failure of lymphopoiesis after adoptive transfer of NF-kappaB-deficient fetal liver cells.

Mice deficient in the p65 subunit of NF-kappaB die during fetal development. Introduction of p50/p65-deficient fetal liver cells into lethally irradiated hosts resulted in a severe deficit of fetal liver-derived lymphocytes and their immediate precursors but an overabundance of fetal liver-derived granulocytes. Surprisingly, simultaneous transplantation of wild-type bone marrow cells rescued the production of p50/p65-deficient lymphocytes. Expression of immunoglobulin K light chains on these rescued NF-kappaB-deficient B lymphocytes was normal. These results suggest that while p50 and p65 do not regulate the maturation of pre-B cells, NF-kappaB mediates the development or survival of an early lymphocyte precursor through regulation of an extracellular factor.

Adoptive Transfer↗

PubMed1997

Complementation of V(D)J recombination deficiency in RAG-1(-/-) B cells reveals a requirement for novel elements in the N-terminus of RAG-1.

RAG-1 is an essential component of the site-specific V(D)J recombinase. A new assay system has revealed a significant contribution of the catalytically dispensible N-terminal region of RAG-1 to recombination activity. The foundation for this system is an Abelson virus-transformed cell line derived from RAG-1(-/-) mice that is dependent on the introduction of exogenous RAG-1 for rearrangement of either plasmid substrates or the endogenous immunoglobulin loci. Use of this line demonstrates that conserved and novel cysteine-containing elements in the N-terminal region are required for full RAG-1 activity when recombination activity is in a RAG-1 dose-responsive range. Our data suggest that the RAG-1 N-terminus enhances the formation of an active recombination complex that facilitates the rearrangement process.

Abelson murine leukemia virus↗

PubMed1997

Simultaneous PET and MR imaging.

We have developed a prototype PET detector which is compatible with a clinical MRI system to provide simultaneous PET and MR imaging. This single-slice PET system consists of 48 2 x 2 x 10 mm3 LSO crystals in a 38 mm diameter ring configuration that can be placed inside the receiver coil of the MRI system, coupled to three multi-channel photomultipliers housed outside the main magnetic field via 4 m long and 2 mm diameter optical fibres. The PET system exhibits 2 mm spatial resolution, 41% energy resolution at 511 keV and 20 ns timing resolution. Simultaneous PET and MR phantom images were successfully acquired.

Equipment Design↗

PubMed1996

Longitudinal behavioral and 6-[18F]fluoro-L-DOPA-PET assessment in MPTP-hemiparkinsonian monkeys.

Biochemical and behavioral criteria were established to determine the long-term stability of a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced unilateral striatal dopamine deficiency in the vervet monkey. At time points over a 12-month period, post-MPTP striatal dopamine synthesis capacity was indexed with 6-[18F]fluoro-L-DOPA (FDOPA)-positron emission tomography. For the MPTP-treated subjects (n = 4), an intrasubject FDOPA influx rate constant (Ki) ratio method of right (lesioned) striatum/left (unlesioned) striatum values was used to assess changes in striatal activity. Striatal FDOPA Ki ratios differed less than 5% between studies conducted at 1-2, 5-7, and 9-11 months post-MPTP; these results indicated a stable MPTP-induced striatal lesion over this time period. At the 5-7 and 9-11 month time points, behavioral indices of the MPTP-induced deficits were obtained within a species-typical group setting. For three of the four subjects, persistent decrements in motoric, affiliative, and vigilance behavior were observed while the frequency of aggression toward group members was increased. At the 9-11 month time point, one subject showed a 30% improvement in the social measures, indicative of a partial recovery from the MPTP-induced behavioral decrements although its striatal FDOPAKi ratio remained unchanged. Thus, behavioral and noninvasive biochemical methods can provide complementary indices to assess individual differences in sensitivity to MPTP-induced deficits. Both types of data are required to determine lesion stability and, subsequently, the efficacy of interventions designed to restore normal function in this primate Parkinsonian model.

Animals↗

PubMed1996

Bayesian reconstruction of PET images: methodology and performance analysis.

We describe a practical statistical methodology for the reconstruction of PET images. Our approach is based on a Bayesian formulation of the imaging problem. The data are modelled as independent Poisson random variables and the image is modelled using a Markov random field smoothing prior. We describe a sequence of calibration procedures which are performed before reconstruction: (i) calculation of accurate attenuation correction factors from re-projected Bayesian reconstructions of the transmission image; (ii) estimation of the mean of the randoms component in the data; and (iii) computation of the scatter component in the data using a Klein-Nishina-based scatter estimation method. The Bayesian estimate of the PET image is then reconstructed using a pre-conditioned conjugate gradient method. We performed a quantitation study with a multi-compartment chest phantom in a Siemens/CTI ECAT931 system. Using 40 1 min frames, we computed the ensemble mean and variance over several regions of interest from images reconstructed using the Bayesian and a standard filtered backprojection (FBP) protocol. The values for the region of interest were compared with well counter data for each compartment. These results show that the Bayesian protocol can produce substantial improvements in relative quantitation over the standard FBP protocol, particularly when short transmission scans are used. An example showing the application of the method to a clinical chest study is also given.

Algorithms↗

PubMed1996

Radiofluorinated L-m-tyrosines: new in-vivo probes for central dopamine biochemistry.

In this work, we introduce 6-[18F]fluoro-L-m-tyrosine (6-FMT) and compare its in-vivo kinetic and bio-chemical behaviors in monkeys and rodents with those of 4-FMT and 6-[18F]fluoro-L-3, 4-dihydroxyphenylalanine (DOPA) (FDOPA). These radiofluorinated m-tyrosine presynaptic dopaminergic probes, resistant to peripheral 3-O-methylation, offer a nonpharmacological alternative to the use of catechol-O-methyltransferase inhibitors. Like FDOPA, 4-FMT and 6-FMT are analogs that essentially follow the L-DOPA pathway of central metabolism. After i.v. administration in nonhuman primates and rodents, these new radiofluorinated m-tyrosine analogs accumulate selectively in striatal structures and allow for the detection of additional innervation sites (e.g., brain stem) rich in aromatic amino acid decarboxylase. Bio-chemical analyses in rodents and monkeys revealed the specificity of their central and peripheral metabolism. Molecular and enzymatic mechanisms involved in their retention in central brain structures are consistent with involvement of dopaminergic neurons. The high signal-to-noise ratios observed make these radiofluorinated m-tyrosine analogs outstanding candidates for probing the integrity of central dopaminergic mechanisms in humans.

Animals↗

PubMed1995

Novel biopolymers for drug discovery.

The solid phase synthesis and generation of libraries of "unnatural biopolymers" is described. These polymers are characterized by novel backbones and building blocks, the properties of which may modify their pharmacological and folding properties.

Biopolymers↗

PubMed1995

Improved signal-to-noise in PET activation studies using switched paradigms.

UNLABELLED: PET activation studies employing the autoradiographic technique and 15O-water or 15O-butanol use the difference between images acquired under baseline conditions and during activation to detect focal changes in cerebral blood flow which occur upon stimulus presentation. Typically, the activating task or baseline conditions are maintained throughout the entire imaging period. Simulations of the kinetics of these freely diffusible tracers suggest there may be an advantage to switching between activation and baseline conditions during the course of the study which results in images which maximize the difference signal rather than seeking to quantitate blood flow. We examine the potential of these switched protocols to increase signal-to-noise (S/N) in PET activation studies. METHODS: We examined S/N in activation studies using both-standard and switched paradigms with a simple switched protocol and dynamic three-dimensional PET data from human subjects. With tracer kinetic simulations, we investigated the sensitivity of the S/N gain to factors such as the shape of the input function, the time at which the conditions are switched and the magnitude of the activation. RESULTS: In human studies of activation sites in the visual cortex, primary motor and premotor areas, S/N improvements of 20%-30% were detected using the switched paradigms. Simulations show that this gain is virtually independent of activation magnitude and that there is a broad time window of 20 sec for making the switch between conditions. To obtain the highest S/N gain, a rapid bolus injection is required. CONCLUSION: Switched paradigms have the potential to significantly increase S/N in PET activation studies. In human studies, the S/N increase averaged 25% which is equivalent to increasing the number of counts collected by 50%. Switched paradigms can be used to maximize the difference signal in many activation studies, and do not preclude the absolute quantitation of blood flow using the standard autoradiographic technique.

Brain↗

PubMed1993

An unnatural biopolymer.

A highly efficient method has been developed for the solid-phase synthesis of an "unnatural biopolymer" consisting of chiral aminocarbonate monomers linked via a carbamate backbone. Oligocarbamates were synthesized from N-protected p-nitrophenyl carbonate monomers, substituted with a variety of side chains, with greater than 99 percent overall coupling efficiencies per step. A spatially defined library of oligocarbamates was generated by using photochemical methods and screened for binding affinity to a monoclonal antibody. A number of high-affinity ligands were then synthesized and analyzed in solution with respect to their inhibition concentration values, water/octanol partitioning coefficients, and proteolytic stability. These and other unnatural polymers may provide new frameworks for drug development and for testing theories of protein and peptide folding and structure.

Amino Acid Sequence↗

PubMed1993

Improved detection of focal cerebral blood flow changes using three-dimensional positron emission tomography.

Removal of the interplane septa and configuration of a typical multislice PET scanner to accept all possible coincidence lines of response leads to a fivefold increase in sensitivity. This can be of value in regional CBF studies using bolus 15O-labeled water injections, allowing the injected dose to be reduced by a factor of 4, while maintaining the same number of noise equivalent counts. Thus, for a given cumulative dose limit, four times as many studies can be performed in a single subject. Data from the three-dimensional Hoffman brain phantom, closely matched to count rates seen in human studies, show that for an identical cumulative dose, the noise in subtraction (stimulus minus baseline) images can be reduced by a factor of 2 using three-dimensional data acquisition, with appropriate fractionation of the dose. This improvement is dependent on axial position due to the sensitivity characteristics of three-dimensional scans; however, there is a significant gain in the signal-to-noise ratio (S/N) in all image planes. Studies performed in a human subject demonstrate how the factor of 2 gain in S/N leads to improved detectability of activation sites in PET subtraction images.

Adult↗

PubMed1993

Attenuation correction using count-limited transmission data in positron emission tomography.

Poisson noise in transmission data can have a significant influence on the statistical uncertainty of PET measurements, particularly at low transmission count rates. In this paper, we investigate the effect of transmission data processing on noise and quantitative accuracy of reconstructed PET images. Differences in spatial resolution between emission and transmission measurements due to transmission data smoothing are shown to have a significant influence on quantitative accuracy and can lead to artifacts in the reconstructed image. In addition, the noise suppression of this technique is insufficient to greatly reduce transmission scan times. Based on these findings, improved strategies for processing count-limited transmission data have been developed, including a method using segmentation of attenuation images. Using this method, accurate attenuation correction can be performed using transmission scan times as low as 2 min without increasing noise in reconstructed PET images.

Heart↗

PubMed1993

Correction and characterization of scattered events in three-dimensional PET using scanners with retractable septa.

Large sensitivity increases are realized in positron emission tomography when the interplane septa are removed and all lines of response acquired. Unfortunately, three-dimensional acquisition results in a large increase in scatter fraction which prevents accurate quantitation. By acquiring short two-dimensional scans prior to three-dimensional ones, scatter distributions can be estimated from differences between lines of response common to both datasets. This initial scatter distribution can be further modified to approximate scatter in the entire three-dimensional dataset. The method was validated with phantom measurements in which absolute activity concentrations were known in all compartments. Following scatter correction, a four-compartment phantom that was nonuniform in activity and density, both axially and transaxially, gave activity concentrations of 0.45 +/- 0.02, 0.31 +/- 0.02, 0.01 +/- 0.01 and 0.01 +/- 0.01 microCi/cc for compartments containing 0.43, 0.29, 0.0 (air) and 0.0 (water) microCi/cc, respectively. Thus, scatter distributions for complex sources can be estimated from image data without lengthy Monte-Carlo simulations. When activity distributions vary slowly with time, this method can be used to correct for scatter in three-dimensional patient studies.

Brain↗

PubMed1992

Evaluation of a 3D reconstruction algorithm for multi-slice PET scanners.

A fully 3D reconstruction algorithm based on filtered backprojection was evaluated for the reconstruction of data obtained with multi-slice positron emission tomography (PET) scanners which have had the septa removed. This algorithm uses forward-projection through the reconstructed images of a 2D subset of the data to complete the 3D dataset thus satisfying the condition of shift invariance. This is followed by 3D filtered backprojection. Axial sampling was doubled by combining adjacent polar angles, thus improving reconstructed axial resolution. The algorithm was tested using real and simulated datasets and gave high quality reconstructions without artifacts over a wide range of imaging conditions. Events are placed accurately throughout the imaging volume as determined by measurements with a MRI/PET registration phantom. The forward-projection step leads to degradation in image resolution due to insufficient axial and transaxial sampling. This effect is amplified if multiple iterations of the algorithm are used, with little decrease in image noise. Changing the filter employed in the initial 2D reconstruction can be used to alter the noise and resolution characteristics of the 3D images. This algorithm has proved very robust at reconstructing 3D PET data and is relatively fast. Those small problems which exist can be attributed to detector sampling problems, especially in the axial direction, which is a consequence of the geometry of these scanners, which are designed primarily for 2D data acquisition.

Algorithms↗

PubMed1992

Design features and performance of a PET system for animal research.

The design features of a PET system designed for animal studies are described and its performance evaluated. The system employs a two-dimensional modular detector array consisting of bismuth germanate detector elements that are 3.5 mm (transaxially) by 6.25 mm (axially) by 30 mm (deep). These arrays are optically coupled to a pair of dual-photo-multiplier tubes (PMT). The detector ring is 64 cm in diameter with a field of view (FOV) of 40 cm by 5.4 cm axially, acquiring 15 slices at 3.4 mm spacing. These features include: (1) digitization of PMT signals from each block for improved position and energy discrimination of coincident events and (2) dual-window energy discrimination for simultaneous but separate acquisition of photopeak and scatter data. Intrinsic resolution averages 3.5 mm at the center of the FOV, while reconstructed resolution (ramp filter) ranges from 3.8 mm at the center of the FOV to 4.6 mm at an 8 cm radius. Axial resolution averages 4.4 and 4.9 mm and sensitivity averages 4.2 and 6.1 kcps/microCi/cc for cross planes and enhanced direct planes, respectively. Randoms fraction is high due to reduced interplane shielding, giving a peak true count rate of 103 kcps for a 10 cm cylinder. Scatter as a fraction of trues is 16% for a 10 cm cylinder at a lower energy threshold of 350 keV. All parameters are sensitive to energy threshold. Spatial resolution improves by 11% transaxially and 9% axially, scatter fraction drops to 10%, and overall sensitivity drops by 48% when the threshold value is increased from 350 keV to 450 keV.

Animals↗

PubMed1991

Measurements of blood-brain barrier permeability in patients undergoing radiotherapy and chemotherapy for primary cerebral lymphoma.

Positron emission tomography (PET) has been used to measure changes in regional blood-brain barrier (BBB) permeability in patients with primary cerebral lymphoma undergoing radiotherapy and chemotherapy. The method employed is to measure the rate of wash-out of a radioactive tracer (68Ga-EDTA) from blood into brain tissue using time-sequence PET imaging. Preliminary studies carried out on patients with more common primary cerebral tumours show that time-activity data are reproducible to approximately 10%. Measurements made in 2 patients with primary cerebral lymphoma treated with initial chemotherapy showed significant changes in permeability in the region of the tumour. Within 5 weeks of the start of treatment, permeability values reached the levels of normal brain. No changes in BBB permeability in normal brain were seen immediately after radiotherapy.

Adult↗

PubMed1990

Quantitative in vivo measurements of tumor perfusion using rubidium-81 and positron emission tomography.

Rubidium-81 (t1/2 = 4.58 hr) was investigated as a tumor perfusion tracer in the VX2 carcinoma implanted into rabbit thigh muscle using a large-area, multiwire proportional chamber positron emission tomography (PET) system. Perfusion was determined using the arterial reference sample method, and the results from PET imaging were compared with postmortem tissue sampling. Absolute quantitation of tumor perfusion was achieved using external probes to estimate local extraction fraction. Redistribution of rubidium-81 (81Rb) was investigated using a dual-tracer technique. Average perfusion was found to be 13.5 and 3.7 ml/min/100 g in tumor and normal muscle, respectively. The extraction fraction as estimated from a two-compartment model ranged from 0.94 to 1.00. No significant redistribution of 81Rb was observed in these tissues. Nine patients with malignancies were studied using 81Rb and PET. Tumor perfusion in four patients with carcinoma of the breast was elevated by a factor of 1.8 (range 1.2-2.3) compared to contralateral normal breast.

Animals↗