E. Tsyganov

Bone phenotype of the aromatase deficient mouse

Estrogens are important for normal bone growth and metabolism. The mechanisms are incompletely understood. Thus, we have undertaken characterization of the skeletal phenotype of aromatase (ArKO) deficient mice. No abnormalities have been noted in skeletal patterning in newborns. Adult ArKO mice show decreased femur length and decreased peak Bone Mineral Density (BMD) with accelerated bone loss by 7 months of age in females. Magnetic resonance microscopy (MR) and microCT (microCT) imaging disclosed decreased cancellous connectivity and reduced cancellous bone volume in ArKO females. Bone formation rate (BFR) is increased in ArKO females and decreased in ArKO males. Estradiol therapy reverses these changes. This anabolic effect of estradiol in the male skeleton is supported by 18-F- Positron Emission Tomography (PET) imaging, which clearly demonstrates decreased spinal uptake, but marked increase after estradiol therapy. Serum IGF-1 levels are high in young female ArKO mice but low in young ArKO males. The reduced BMD in ArKO females, despite the presence of elevated serum IGF 1, suggests that other mechanism(s) are operative. There is increased B-cell lymphopoiesis in adult female ArKO bone marrow cells. These results show that ArKO mice show the effects of estrogen deficiency on bone growth, mass, metabolism, microarchitecture and the hematopoietic microenvironment.

Vascular imaging of solid tumors in rats with a radioactive arsenic-labeled antibody that binds exposed phosphatidylserine.

Purpose: We recently reported that anionic phospholipids, principally phosphatidylserine, become exposed on the external surface of vascular endothelial cells in tumors, probably in response to oxidative stresses present in the tumor microenvironment. In the present study, we tested the hypothesis that a chimeric monoclonal antibody that binds phosphatidylserine could be labeled with radioactive arsenic isotopes and used for molecular imaging of solid tumors in rats. Experimental Design: Bavituximab was labeled with 74As (β+, T1/2 17.8 days) or 77As (β−, T1/2 1.6 days) using a novel procedure. The radionuclides of arsenic were selected because their long half-lives are consistent with the long biological half lives of antibodies in vivo and because their chemistry permits stable attachment to antibodies. The radiolabeled antibodies were tested for the ability to image subcutaneous Dunning prostate R3227-AT1 tumors in rats. Results: Clear images of the tumors were obtained using planar γ-scintigraphy and positron emission tomography. Biodistribution studies confirmed the specific localization of bavituximab to the tumors. The tumor-to-liver ratio 72 h after injection was 22 for bavituximab compared with 1.5 for an isotype-matched control chimeric antibody of irrelevant specificity. Immunohistochemical studies showed that the bavituximab was labeling the tumor vascular endothelium. Conclusions: These results show that radioarsenic-labeled bavituximab has potential as a new tool for imaging the vasculature of solid tumors.

AVALANCHE PHOTO DIODE WITH LOCAL NEGATIVE FEEDBACK SENSITIVE TO UV, BLUE AND GREEN LIGHT

Abstract A new type of avalanche photo diode with negative feedback based on a Metal-Resistor-Semiconductor (MRS) structure and sensitive to UV, blue and green light was tested using a 137 Cs β-source with electrons impinging a front surface of the detector, and also with 90 Sr β-source illuminating a 1 mm diameter scintillating fiber. MRS detectors of this type are built on low resistivity n-silicon. The sensitivity of the detector is calibrated using the ionization loss of 137 Cs β-electrons. We conclude that these detectors have characteristics well suited to medical imaging applications, in particular wavelength dependence, quantum efficiency and sensitivity, and intrinsic multiplication.

3D position readout from thick scintillators

AbstractAnoveltechniquehasbeendevelopedandtestedforthethree-dimensionalmeasurementofpositioninSPECT-PETdetectors.Resultsarepresentedfor2and20mmthickNaI(Tl)planarcrystals.Inaplaneofcrystal,acoordinateresolutionofabout1mm(rmserror)isdemonstrated.Thedepthofinteraction(DOI)ismeasuredwithanrmserrorofabout2mmusinglightconeparameters.r 2002ElsevierScienceB.V.Allrightsreserved. PACS: 29.40.Mc;29.40.GxKeywords: Scintillationdetectors;Depthofinteraction;Positionresolution 1. IntroductionThree-dimensionalmeasurementsofinteractionpositions of g-particles or X-rays is a verychallenging task. In high resolution positronemissiontomography(PET),itisveryimportanttoknowthedepthofinteraction(DOI),toavoidthe so-called parallax errors which degrade theimageresolutionfromthecentertotheouteredge.Severalmethodshavebeenproposedtosolvetheproblem. These include the utilization of atemperaturegradientalongthecrystal[1];theuseofaphoswichdesign[2]andtheconnectionoftwoendsofthe crystals toseparatephotosensors[3].Othermethodsincludetheuseofalightabsorbingmaterial around each crystal [4] or drug a lightabsorbing medium between the detector [5].However,allthemethodsrequireeitherextensiveworkwithdetectorcrystalsoradditionalelectro-nics, and the DOI resolution is still not satisfac-tory.Weemployyetanotherapproachtosolvetheproblem.This work is a continuation of the researchdescribed in Ref. [6]. In a search for an optimaldesign of a multi-modality scintillating detector,we have studied several geometries of positionsensitivedevices.Amongcurrentlyavailablecrys-tals, NaI(Tl) crystal is a good candidate for thecombined PET-SPECT modality. It has a highdensity and a good light yield with an emissionwavelengthspectrumwellmatchedtothephoto-cathode of a photomultiplier tube. To avoidhydrophilicdeteriorationofNaI,ourtestcrystalswere packed in metal–glass or glass–glass envel-opes.LimitationsinPETimagingduetoslowlightemission of NaI(Tl) crystals could be overcomeusingasectioneddesignwithtile-typescintillators.

UTSW Small Animal Positron Emission Imager

A Small Animal Imager (SAI) for PET has been designed, built, tested in phantoms, and applied to investigations in mice and rats. The device uses principles based on gamma-ray induced scintillation in crossed fiber optic detectors connected to Position Sensitive Photomultiplier Tubes (PSPMT). Each detector consists of an epoxied stack of 28 layers of 135 round 1 mm BCF-10 scintillating plastic fibers. The overlap region forms a 13.5times13.5times2.8 cm3 detector volume. Scintillating light from the fibers is detected by two (X and Y directions) Hamamatsu R-2486 PSPMTs with 16 anode wires in each of two orthogonal directions. A centroid-finding algorithm gives the position of a light cluster on the face (photocathode) of a PSPMT. The accuracy of the reconstruction of an interaction position is essentially independent of light cluster position. This translates to a nearly isotropic photon response for the entire detector. The system has been used to test several 3D image reconstruction algorithms, software modifications, and improvements. The sensitivity (~12.6 cps/kBq at 9 cm inner diameter) and sub-millimeter spatial resolution (better than 1 mm in phantoms) obtained with an iterative algorithm incorporating system modeling make the SAI a relatively inexpensive high performance animal imager. The SAI is currently being used for imaging experiments in mice and rats

Comparison of LSO samples produced by Czochralsky and modified Musatov methods

Abstract This study is based on test results of 30 LSO samples produced by the POLUS Research Institute in Moscow, Russia, for the University of Texas Southwestern Medical Center at Dallas. Samples were produced by the Czochralsky and the modified Musatov methods. Pulse-height spectra from 22 Na positron annihilations were analyzed and conclusions are drawn. After some minor corrections to the modified Musatov technology, samples could be recommended for use in PET systems.

SPECT electronic collimation resolution enhancement using chi-square minimization

An electronic collimation technique is developed which utilizes the chi-square goodness-of-fit measure to filter scattered gammas incident upon a medical imaging detector. In this data mining technique, Compton kinematic expressions are used as the chi-square fitting templates for measured energy-deposition data involving multiple-interaction scatter sequences. Fit optimization is conducted using the Davidon variable metric minimization algorithm to simultaneously determine the best-fit gamma scatter angles and their associated uncertainties, with the uncertainty associated with the first scatter angle corresponding to the angular resolution precision for the source. The methodology requires no knowledge of materials and geometry. This pattern recognition application enhances the ability to select those gammas that will provide the best resolution for input to reconstruction software. Illustrative computational results are presented for a conceptual truncated-ellipsoid polystyrene position-sensitive fibre head-detector Monte Carlo model using a triple Compton scatter gamma sequence assessment for a 99mTc point source. A filtration rate of 94.3% is obtained, resulting in an estimated sensitivity approximately three orders of magnitude greater than a high-resolution mechanically collimated device. The technique improves the nominal single-scatter angular resolution by up to approximately 24 per cent as compared with the conventional analytic electronic collimation measure.

Compact Compton camera design: parameters and imaging algorithms

This study presents results of Monte Carlo simulations of a compact Compton camera design using the GEANT-based computer code. The proposed system is a sensitive SPECT device made of semiconductor detectors capable of providing angular resolutions of about 1 mrad. To accurately model the camera, the GEANT code was modified to take into account pre-collision motion of elections, the so-called Doppler effect. A new algorithm for three-dimensional image reconstruction based on clustering of individual events has been developed and proven on clustering of individual events has been developed and proven with Monte Carlo phantoms for a Compton camera and with phantoms and small animal studies for a PET machine.

A superfiber for position sensitive detectors

Abstract Scintillating fibers are being used more and more in science and medicine to provide precise coordinate measurement systems for elementary particles and X-ray detection. However, low light collection efficiency (3–4% per direction typically) is still the most limiting factor. In this paper we present results of Monte Carlo calculations to illustrate some peculiarities of light collection in round fibers. According to our analyses, by certain modifications light collection in round scintillating and waveshifting fibers could be increased to about 20% per direction.

Reconstruction Algorithm with Resolution Deconvolution in a Small-Animal PET Imager

A small-animal PET imaging device has been developed at the University of Texas Southwestern Medical Center at Dallas using scintillating 1-mm round BCF10 fibers and small admixture of CsF microcrystals between the fibers [Antich, 1990, Atac, 1991, Fernando, 1996 ]. The fiber core is polystyrene (C 8 H 8 )n doped with butyl-PBD and dPOPOP. The fibers are clad in a non-scintillating lucite cladding. The scintillation mechanism can be either from the excitation of π electrons in the butyl-PBD benzene ring in the fiber or from excitation within the microcrystals. In both cases, the emitted light is compatible with the optimal spectral response of standard photomultiplier cathodes. For a 511 keV photon in plastic,the photo-absorption is small, and Compton scatter interactions are dominant. The scattered electrons give up their energy well within a fiber diameter, but wave-shifting produces light in proximal fibers. The current imager uses the 2-fold coincident detection of a single event in 2 orthogonal fibers of 1-mm diameter to detect the location and the energy transferred at a point within the detector. Two sets of fibers each 60 cm in length and 1 mm in diameter were used to construct two alternating, mutually orthogonal sets of 14 planar arrays of 135 fibers each. In this detector, the planar fiber arrays are arranged along two alternating mutually orthogonal (X and Y)axes and are stacked along a third (Z). Scintillating light from the fibers is detected by two (X and Y directions) Hamamatsu R-2486 Position Sensitive Photomultiplier Tubes (PSPMT). A single-ended readout scheme is used, where the X,Z and Y,Z interaction positions in a detector are determined from coincident detection in the two PSPMT. The precision of the detection of the interaction point depends upon PSPMT performance and software filters.