Eric L. Bradley

SPECT-CT system for small animal imaging

The Detector Group at the Thomas Jefferson National Accelerator Facility (Jefferson Lab) and the Biology, Physics, and Applied Sciences Departments at the College of William and Mary are collaborating on the development of a miniature dual modality SPECT-CT system for mouse imaging. The detector heads of the SPECT sub-system are designed to be capable of imaging the gamma- and X-ray emissions (28-35 keV) of the radioactive isotope iodine-125 (I-125). Two different sets of I-125 imaging detectors are configured on a gantry that has an open-barrel type design. One set of detector heads is based on the 1-in square Hamamatsu R5900-M64 position sensitive photomultiplier tube coupled to crystal scintillator arrays. The other detector heads configured on the gantry are two 5-in diameter Hamamatsu R3292-based compact gamma cameras. The X-ray radiographic projections are obtained using a LIXI Inc. model LF-85-503-OS X-ray imaging system that has an active area of 5.5 cm in diameter. The open-barrel shaped gantry facilitates the positioning of various mini gamma-ray imaging detectors and the X-ray system. The data acquisition and gantry control is interfaced through a Macintosh G3 workstation. Preliminary SPECT reconstruction results using the R5900 based detector are presented.

Design features and performance of a CsI(Na) array based gamma camera for small animal gene research

The authors report on the development of a radiation imaging system based on a matrix of CsI(Na) scintillating crystals. This detector system has been optimized for high resolution radiation imaging of the distribution of iodine 125 (/sup 125/I) in a laboratory animal. The radioisotope /sup 125/I is readily available as a label to molecular biology probes that can be used in gene research. Iodine 125 decays via electron capture emitting a 35 keV gamma-ray with the prompt emission of several 27-32 keV X-rays. A coincidence condition can be set to detect the /sup 125/I decays thus reducing background radiation contribution to the image. The system utilizes the Hamamatsu 5 inch diameter 3292 position sensitive photomultiplier tube (PSPMT) coupled to the CsI(Na) matrix and a custom built high resolution copper-beryllium collimator. A conventional photomultiplier coupled to a NaI(Ti) crystal scintillator is used to detect the coincident radiation resulting from the decay of /sup 125/I.

Development of a novel radiation imaging detector system for in vivo gene imaging in small animal studies

We report preliminary results from a prototype of radiation imaging technology which takes advantage of the emission properties of the radioisotope iodine /sup 125/I as the probe. The detector system utilizes crystal scintillators and a position sensitive photomultiplier tube. Iodine 125 decays via electron capture emitting a 35-keV gamma ray with the prompt emission of several 27-32-keV K/spl alpha/ and K/spl beta/ shell X-rays. Because of this, a coincidence condition can be set to detect the /sup 125/I decay, thus reducing background radiation contribution to the image. The prototype detector we report has a limited sensitivity and detection area because of the size of the scintillators and photomultiplier tubes, yet it performed well enough to demonstrate the viability of this method for imaging /sup 125/I in a mouse. Mouse imaging studies of iodine uptake by the thyroid and melatonin binding have been done with this detector system using doses of /sup 125/I alone or attached to the melatonin. Many studies in molecular biology follow the expression and regulation of a gene at different stages of an organisms development or under different physiological conditions. Molecular biology research could benefit from this detection system by utilizing /sup 125/I-labeled gene probes.

A compact gamma camera for biological imaging

A compact detector, sized particularly for imaging a mouse, is described. The active area of the detector is approximately 46 mm /spl times/ 96 mm. Two flat-panel Hamamatsu H8500 position-sensitive photomultiplier tubes (PSPMTs) are coupled to a pixellated NaI(Tl) scintillator which views the animal through a copper-beryllium (CuBe) parallel-hole collimator specially designed for /sup 125/I. Although the PSPMTs have insensitive areas at their edges and there is a physical gap, corrections for scintillation light collection at the junction between the two tubes results in a uniform response across the entire rectangular area of the detector. The system described has been developed to optimize both sensitivity and resolution for in-vivo imaging of small animals injected with iodinated compounds. We demonstrate an in-vivo application of this detector, particularly to SPECT, by imaging mice injected with approximately 10-15 /spl mu/Ci of /sup 125/I.

Lifelong exposure to methylmercury disrupts stress‐induced corticosterone response in zebra finches (Taeniopygia guttata)

Mercury can disrupt the endocrine systems of mammals and fish, but little is known about its effects on avian hormones. The authors employed an experimental manipulation to show that methylmercury suppresses the stress-induced corticosterone response in birds, an effect previously unreported in the literature. Corticosterone regulates many normal metabolic processes, such as the maintenance of proper blood glucose levels during stressful daily fasting; an inability to increase corticosterone levels in response to stressors renders a bird less able to face a wide array of environmental challenges. The authors studied reproductively mature zebra finches that had been exposed to 0.0 µg/g, 0.3 µg/g, 0.6 µg/g, 1.2 µg/g, or 2.4 µg/g (wet wt) dietary methylmercury throughout their life (i.e., from the egg onward). In contrast to some field studies, the present study found no significant change in baseline plasma corticosterone concentrations attributable to chronic methylmercury exposure. However, a comparison between the baseline corticosterone levels and levels after 30 min of handling stress revealed that the ability of birds to mount a stress response was reduced with increasing blood total mercury concentration. These results are consistent with adrenal corticoid disruption caused by chronic mercury exposure and mirror a similar study on free-living nestling songbirds exposed to environmental mercury.

A Comparison of the Adrenal Histology, Reproductive Condition, and Serum Corticosterone Concentrations of Prairie Deermice (Peromyscus maniculatus bairdii) in Captivity

Serum corticosterone concentrations and adrenal histology were studied in deermice maintained in laboratory populations or as pairs. Animals from populations had highly significantly smaller reproductive organs than did controls. Both sexes from populations had smaller absolute adrenal weights and histological evaluation revealed smaller adrenal cortical and medulla area compared to controls. However, the relative adrenal weight was larger in both sexes of animals from populations and the serum corticosterone concentrations were also significantly higher in both sexes of population-inhibited animals when compared with controls. Several correlations of corticosterone concentration with reproductive condition are presented and there is a discussion of the relationship of increased corticosterone concentration with reproductive inhibition.

Coincident radiation imaging of iodine 125 for in vivo gene imaging in small animals

Progress has been made towards a novel in vivo gene imaging technology which take advantage of the emission properties of 125I as the label for a gene specific probe. The radioisotope 125I decays via electron capture emitting a 35 keV γ-ray with the prompt emission of several 27–32 keV Kα and Kβ shell X-rays. Hence, a coincidence detection condition can be implemented to detect the 125I decays, thus reducing the background contribution and enhancing the possibility of detecting minute amounts of the isotope. The detector system utilizes crystal scintillators and a position-sensitive photomultiplier tube. Currently, studies in molecular biology and gene regulation follow the expression of a particular gene at a given instant in time. Presently, in situ hybridization and immunochemical assays are available to observe the spatial patterning of gene expression in an organism at any one instant in time for one organism but one must sacrifice the organism to make a measurement, essentially taking a single snap-shot of the state of expression of the gene of interest. It is hoped that this detection scheme will make possible gene imaging in live animals for extended periods of time.

Ovulation in Peromyscus maniculatus bairdi under Laboratory Conditions

This study was designed to determine whether ovulation in Peromyscus maniculatus bairdi is induced or spontaneous, and to determine the accuracy with which vaginal smears reflect the ovarian cycle. Ovarian histology, vaginal smears, and serum LH concentrations were compared among females inseminated 30 min or 24 h previously or housed alone. Deermice most frequently copulate in the dark period of their daily light cycle, and have variable vaginal smear patterns. Ovulation was spontaneous in the absence of tactile contact with the male and was not consistently related to the time of copulation. Serum LH values indicated a preovulatory surge. Marked variability was found in vaginal smear patterns, ovarian histology, and plasma LH concentrations.

Studies on the nature of reproductive inhibition in animals from laboratory populations of prairie deermice (Peromyscus maniculatus bairdi): Serum LH and FSH concentrations

Abstract Serum LH and FSH concentrations and gonadal condition in deermice maintained in laboratory populations or as pairs were determined: 1. 1. Animals taken from populations had significantly smaller body, gonad and sexual accessory weights when compared with controls. 2. 2. Histological evaluation of the gonads revealed significantly fewer spermatids in the testes and significantly fewer Type 8 follicles and corpora lutea in ovaries from population animals compared with controls. 3. 3. Serum LH concentrations were not significantly different among males, but were significantly lower in population females compared with their controls. 4. 4. Serum FSH concentrations were significantly higher in population males and population females compared with their controls.

Correlations between serum corticosterone concentration and reproductive conditions in the white-footed mouse (Peromyscus leucopus noveboracensis).

1. Adrenal size and activity in reproductively inhibited young born into laboratory populations of the white-footed mouse were examined. Measurements were made of body weight, reproductive organ weight and adrenal weight. Serum corticosterone was measured by radioimmunoassay. 2. Data from reproductively inhibited animals were compared with corresponding values from reproductively capable animals of the same sex. The mean paired testis and seminal vesicle, or paired ovary and uterus, weights, were significantly reduced in reproductively inhibited animals of both sexes. The paired adrenal weights were not different in any comparison. 3. Reproductively inhibited males selected from laboratory populations had a mean corticosterone concentration that was significantly higher than the corresponding value for reproductively capable males. Females showed no significant difference in mean serum corticosterone concentrations. 4. The results are discussed in relation to earlier studies in two species of Peromyscus and the apparent paradox of elevated serum corticosterone in the absence of adrenal hypertrophy.