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Introduction The α v β 3 integrin, which is expressed by angiogenic epithelium and some tumor cells, is an attractive target for the development of both imaging agents and therapeutics. While optimal implementation of α v β 3 -targeted therapeutics will require a priori identification of the presence of the target, the clinical evaluation of these compounds has typically not included parallel studies with α v β 3 -targeted diagnostics. This is at least partly due to the relatively limited availability of PET radiopharmaceuticals in comparison to those labeled with 99m Tc. In an effort to begin to address this limitation, we evaluated the tumor uptake of 99m Tc-NC100692, a cyclic RGD peptide that binds to α v β 3 with ~1-nM affinity, in an α v β 3 -positive tumor model as well as its in vivo specificity. Methods MicroSPECT imaging was used to assess the ability of cilengitide, a therapeutic with high affinity for α v β 3 , to block and displace 99m Tc-NC100692 in an orthotopic U87 glioma tumor. The specificity of 99m Tc-NC100692 was quantitatively evaluated in mice bearing subcutaneous U87MG tumors, by comparison of the biodistribution of 99m Tc-NC100692 with that of the non-specific structural analogue 99m Tc-AH-111744 and by blocking uptake of 99m Tc-NC100692 with excess unlabeled NC100692. Results MicroSPECT imaging studies demonstrated that uptake of 99m Tc-NC100692 in the intracranial tumor model was both blocked and displaced by the α v β 3 -targeted therapeutic cilengitide. Biodistribution studies provided quantitative confirmation of these imaging results. Tumor uptake of 99m Tc-NC100692 at 1h post-injection was 2.8±0.7% ID/g compared to 0.38±0.1% ID/g for 99m Tc-AH-111744 ( p 99m Tc-NC100692 uptake by pre-injecting the mice with excess unlabeled NC100692 reduced tumor uptake by approximately five-fold, to 0.68±0.3% ID/g ( p =0.01). Conclusion These results confirm that 99m Tc-NC100692 does, in fact, target the α v β 3 integrin and may, therefore, be useful in identifying patients prior to anti-α v β 3 therapy as well as monitoring the response of these patients to therapy.

Metal radionuclide solutions at neutral pH adhere to plastic containers. Adsorption of radionuclides on the walls of phantoms leads to a nonuniform activity distribution, which could adversely affect imaging studies, as well as phantom-based validations of absorbed dose calculations used in radioimmunotherapy, requiring accurate knowledge of the underlying activity distribution. In the work reported here, the authors determined the degree of metal chelation required to minimize metallic radionuclide oxide formation and adsorption on phantom walls in order to yield more reliable experimental data for validating image-based dosimetry. Using hollow spherical plastic phantoms, the authors evaluated three different radionuclides, I-131, In-111, and Y-90, in solutions containing three different concentrations of the chelator, ethylenediaminetetraacetate (EDTA). Adsorption to plastic walls was determined using microSPECT imaging and/or by counting aliquots of solutions. Reconstructed images and measurements of I-131 activity showed that it was uniformly distributed within all spheres; however, images of In-111 in 0.25-microM EDTA indicated that the activity concentration near the wall was much higher than that in the middle of the sphere. The decrease in activity concentration near the center of the spheres was approximately 47%. Y-90 in 0.25-microM EDTA behaved similarly; the activity concentration of Y-90 decreased by 46%. For an In-111 or Y-90 radioactivity concentration of 0.74 MBq/mL, a 2.5-microM EDTA solution was required to achieve a uniform distribution, suggesting that, under our experimental conditions, approximately 700 EDTA molecules were required for each radiometal atom to prevent precipitation and adsorption on poly(methylmethacrylate). For certain radiometals, e.g., In-111 or Y-90, adequate chelation is essential to achieve uniform activity concentration values and homogeneous distribution within the phantom compartments.

We assessed improvements in performance in detection and estimation tasks due to a novel brain single photon computed tomography collimator. Data were acquired on the CeraSPECT{sup TM} scanner using both new and standard collimators. The new variable focusing collimator SensOgrade{sup TM} samples the projections unequally, with central regions more heavily represented, to compensate for attenuation of counts from central brain structures. Furthermore, it utilizes more of the cylindrical crystal surface. Two phantom studies were performed. The first phantom was a 21-cm-diameter cylindrical background containing nine spheres ranging from 0.5 to 5 cm{sup 3} in volume. {sup 99m}Tc sphere to background activity ratio was 10:1. Twenty-nine 10-min datasets were acquired with each collimator. The second phantom was the Radiology Support Devices (Long Beach, CA) striatal phantom with striatal-background ratios of 10:1 on the left and 5:1 on the right. Twenty-nine 4-min datasets were acquired with each collimator. Perfusion imaging using {sup 99m}Tc-HMPAO was also performed in three healthy volunteers using both collimators under identical simulations. Projections were reconstructed by filtered backprojection with an unwindowed ramp filter. The nonprewhitening matched filter signal-to-noise ratio (NPW-SNR) was computed as a surrogate for human performance in detecting spherical lesions. Sphere activity concentration, radius, and locationmore » coordinates were simultaneously estimated by fitting images to an assumed model using an iterative nonlinear algorithm. Resolution recovery was implicit in the estimation procedure, as the point spread function was incorporated into the model. NPW-SNR for sphere detection was 1.5 to 2 times greater with the new collimator; for the striatal phantom the improvement in SNR was 54%. The SNR for estimating sphere activity concentration improved by 46 to 89 % for spheres located more than 5 cm from the phantom center. Images acquired with the standard collimator were too noisy in the central regions to allow estimation of sphere activity. In {sup 99m}Tc-HMPAO human studies, SNR was improved by 21 to 41 % in the cortex, 66% in the basal ganglia, and 74% in the thalamus. The new collimator leads to substantially improved detection and estimation performance throughout the brain. The higher sensitivity will be particularly important for dynamic imaging.« less

Simultaneous dual isotope imaging (/sup 99m/Tc//sup 123/I) has potential clinical applications but has not been implemented in the clinic. The aim of this work was to design an artificial neural network (ANN) for crosstalk and scatter correction using a smaller number of energy windows (8) than we had previously proposed (26) to allow implementation on some clinical cameras, and to validate our approach using realistic Monte Carlo simulations and anthropomorphic brain phantom acquisitions. Monte Carlo simulations of dual isotope SPECT studies of a digital brain phantom and physical acquisitions of the striatal brain phantom were used to validate our approach. Corrected projections were reconstructed using an iterative ordered subsets expectation maximization (OSEM) algorithm that modeled nonuniform attenuation and variable collimator response in the projector/backprojector. Results: In Monte Carlo simulations, ANN26 and ANN8 yielded similarly accurate quantitation of /sup 123/I activity (bias

The authors assessed the potential performance of three commercial SPECT systems in simulated, but realistic, imaging tasks related to the diagnosis and management of Parkinson's disease (PD). Images of I-123 altropane activity distributions in normal and PD brains were modeled assuming values from the literature for striatal sizes and activity concentrations, as well as for nonspecific activity. Imaging characteristics of the three systems were determined by phantom studies. The expected distributions of estimates of activity concentration and striatal volume were based on covariance matrices determined by the Cramer-Rao lower bounds calculated for a simultaneous estimation of these two parameters, as well as background activity concentration. Potential performance in several binary classification tasks was assessed by fitting ROC curves to simulated likelihood ratios for 5000 'subjects' in each category. For all conditions studied, ROC areas were similar for the higher-resolution instruments and lower for the lower-resolution system. These results imply a diagnostic advantage for higher-resolution systems in imaging tasks related to PD.

Three algorithms for scatter compensation in Tc-99m brain single-photon emission computed tomography (SPECT) were optimized and compared on the basis of the accuracy and precision with which lesion and background activity could be simultaneously estimated. These performance metrics are directly related to the clinically important tasks of activity quantitation and lesion detection, in contrast to measures based solely on the fidelity of image pixel values. The scatter compensation algorithms were (a) the Compton-window (CW) method with a 20% photopeak window, a 92-126 keV scatter window, and an optimized "k-factor," (b) the triple-energy window (TEW) method, with optimized widths of the photopeak window and the abutting scatter window, and (c) a general spectral (GS) method using seventeen 4 keV windows with optimized energy weights. Each method was optimized by minimizing the sum of the mean-squared errors (MSE) of the estimates of lesion and background activity concentrations. The accuracy and precision of activity estimates were then determined for lesions of different size, location, and contrast, as well as for a more complex Bayesian estimation task in which lesion size was also estimated. For the TEW and GS methods, parameters optimized for the estimation task differed significantly from those optimized for global normalized pixel MSE. For optimal estimation, the CW bias of activity estimates was larger and varied more (-2% to 22%) with lesion location and size than that of the other methods. The magnitude of the TEW bias was less than 7% across most conditions, although its precision was worse than that of CW estimates. The GS method performed best, with bias generally less than 4% and the lowest variance; its root-mean square (rms) estimation error was within a few percent of that achievable from primary photons alone. For brain SPECT, estimation performance with an optimized, energy-based, subtractive correction may approach that of an ideal scatter-rejection procedure.

Increasing evidence suggests that the dopamine transporter, localized on dopamine neurons, is a marker for a number of physiological and pathological states (KaufmanandMadras, 1991,1993; Madras et al., 1990a, Schoemaker et al., 1985; Singer et al., 1991). With the development of sensitive probes, brainimaging and mea- surement of the transporter have become feasible in re- cent years (Brownell et al., in press; Innis et al., 1991; Frost et al., 1993; Madras et al., 1991; Morns et al., sub- mitted; Seibyl et al., 1995; van Dyke et a1.,1995; Wonget al., 1993,1995). Drugs of many chemical classes, includ- ing cocaine, bind to the dopamine transporter (Seeman, 1993). Nevertheless, effective imaging agents have been developed almost exclusively from the phenyltropane analogue of cocaine WIN 35,428 or CFT, a potent dopa- mine transport inhibitor (Clarke et al., 1973; Heikkila et al., 1979). The impetus for developing [llC]WIN 35,428 as a PET ligand (Hantraye et al., 1992; Madras, 1994; Madras et al., 1991, 1994; Wong et al., 1993; Meltzer et al., 1993) and y-emitting analogues for SPECT imaging (e.g., RTI-55, the 4-iodophenyl analogue of WIN 35,428, Canfield et al., 1990; Boja et al., 1991; Innis et al., 1991) arose directly from our observations of the binding of WIN 35,428 to the dopamine transporter. Unlike previ- ous dopamine transport inhibitors (noncocaine conge- ners) proposed for brain imaging(Kuhar et a1.,1990), the radiolabeled form of WIN 35,428 binds to the dopamine transporter in brain striatum with very low levels of non- specific binding (Madras et al., 1989a,b) and distributes principally to dopamine-rich regions of brain, as we re- ported in 1989 (Canfield et al., 1989) and subsequently (Canfield et al., 1990; Kaufman et al., 1991; Kaufman and Madras, 1992). SPECT imaging techniques are more practical than PET for routine clinical studies because of the lesser

The advantages of simultaneous acquisition of Tc-99m and Tl-201 myocardial perfusion SPECT images can be fully realized only if the effects of the Tc-99m agent can be accurately removed from the Tl-201 image. The authors and others have previously reported simultaneous dual-isotope techniques for cardiac studies which make use of a third energy-window to estimate the Tc-99m scatter to be subtracted from the Tl-201 window. The authors have recently demonstrated, however, using a Monte Carlo program which simulates all details of the photon transport, that lead X-rays produced in the collimator may also contribute significantly to contamination in the Tl-201 window. The spatial distribution of the Tc-99m scattered photons differs from that of the lead X-rays. Therefore, the authors modified their correction technique so that, at each projection angle, the contaminant image to be subtracted from the image in the Tl-201 window was estimated as a linear combination of a scatter-window (90-110 keV) image, blurred by a 2D Gaussian filter, and the Tc-99m photopeak image, blurred by a different Gaussian filter. For simulated data which included 'liver' activity and non-uniform 'lung' attenuation, the improved dual-window subtraction technique provided a more accurate estimate of the true Tl-201 image, with less image noise, than did the single-window correction. >

When evaluating small-animal imagers, small pointlike sources (

Increasing the number of pinholes in small-animal SPECT significantly improves its count sensitivity. When the detector(s) are small, however, overlapping of projections (multiplexing) from different pinholes is unavoidable and can amplify noise in reconstructed images. We have evaluated the performance of two multi-pinhole systems, one with and one without multiplexing, for a prototypical tumor-imaging task. We prepared seven beads (∼1.8-mm diameter) to mimic tumors labeled with Tc-99m. A uniform gelatin phantom was used to simulate normal background tissue. The tumor-to-normal tissue ratio was ∼6:1, and each bead contained ∼1 μCi. The first scanner, equipped with two 0.8-mm pinholes on each of three heads (HMS-0.8), acquired only non-overlapping projections. We also scanned the phantom using 1.6mm pinholes (HMS-1.6) The second scanner had 9 pinholes on each of four heads, and allowed multiplexing. To compensate for decay, the phantom was scanned for 50 min on HMS-0.8, 58 min on HMS-1.6, 82 min on NanoSPECT/CT with 1.4 mm pinholes (Nano-1.4), and 102 min with 1.0 mm pinholes (Nano-1.0). A total of 30 (24) angular projections were acquired with HMS (Nano); these were reconstructed using 10 OSEM subsets for HMS, and 4 subsets for Nano. The mean voxel value in each sphere, and the mean and standard deviation in a large VOI in the background, were used to compute the signal-to-noise ratio (SNR) and contrast of each bead. The relative noise in the background was also calculated. The systems with and without multiplexing yielded similar image quality and average bead SNR, especially for HMS-0.8 and Nano-1.0. Both systems yielded very similar SNR values, despite the fact that the multiplexed system acquired data using 36 pinholes, while the non-multiplexed system had only 6 pinholes. The multiplexed acquisition did not seem to adversely affect the image contrast of the spherical tumors.

Planar scintigraphy using (99m)Tc-labeled methylene diphosphonate ((99m)Tc-MDP) has been established as a method for evaluating mandibular growth and asymmetry. However, (99m)Tc-MDP single photon emission computed tomography (SPECT) provides improved image contrast and quantitative capability potentially allowing the clinician to make a more accurate assessment of the stage of activity of normal and asymmetric mandibular growth. The purpose of this study was to utilize (99m)Tc-MDP SPECT in normal subjects to develop a standardized approach to imaging the mandible that could subsequently be used to evaluate patients with potential for mandibular growth abnormalities.Thirty-two patients (22 females, 10 males, 8-25 years of age, mean of 14 years) having (99m)Tc-MDP bone scans (7.4 MBq/kg, maximum of 518 MBq) for indications not involving the head were asked to have an additional SPECT that included the mandibular condyles. Internal (clivus) and external (source of known activity included within the field of view) standards were both investigated. Two- and three-dimensional (2-D and 3-D) regions of interest (ROI) were drawn over each condyle and the clivus in a single slice containing the maximum pixel value within the structure. A 3-D ROI was also drawn about the external standard. Maximum and average pixel values within the 2-D and 3-D ROIs were recorded.Correlation analysis indicated that essentially the same information was obtained whether the maximum or average pixel value within a 2-D or 3-D ROI was used. The right to left ratio provided a parameter that can be used to assess the magnitude of mandibular metabolic asymmetry. Use of an external standard provides the potential for quantifying condylar uptake for assessment of the activity of mandibular growth. Normal ranges for different age groups were determined for condylar uptake using both internal and external standards.(99m)Tc-MDP SPECT provides a quantitative method for assessing mandibular condylar uptake as a reflection of the activity of mandibular growth. The maximum pixel value of a 2-D ROI using external standardization and the right to left ratio of the condylar uptake provide the potential for quantitative evaluation of patients with mandibular asymmetry. These parameters will be further evaluated in an upcoming clinical investigation.

Serial measurement of the glomerular filtration rate (GFR) is recognized as an important assessment of the status of kidney function for individuals in certain disease states and especially for those undergoing chemotherapy. To be clinically useful the method used to measure GFR must compare favorably to the GFR gold standard, which is the urinary clearance of inulin, and the variance between successive serial measurements must be kept small.

In some instances patients present with thyroid cancer that does not seem to fit the usual treatment guidelines as set forth in conventional texts. For example, there may be an unusual distribution of thyroid remnants or metastases or there sometimes are extensive metastases to the lung or other organs. In these cases knowledge about regional uptake of therapeutic iodine-131 (131I) is useful.

To evaluate the dose from the computed tomographic (CT) portion of positron emission tomography (PET)/CT to determine minimum CT acquisition parameters that provide adequate attenuation correction.Measurements were made with a PET/CT scanner or a PET scanner, five anthropomorphic phantoms (newborn to medium adult), and an ionization chamber. The CT dose was evaluated for acquisition parameters (10, 20, 40, 80, 160 mA; 80, 100, 120, 140 kVp; 0.5 and 0.8 second per rotation; 1.5:1 pitch). Thermoluminescent dosimetry was used to evaluate the germanium 68/gallium 68 rod sources. A phantom study was performed to evaluate CT image noise and the adequacy of PET attenuation correction as a function of CT acquisition parameters and patient size.The volumetric anthropomorphic CT dose index varied by two orders of magnitude for each phantom over the range of acquisition parameters (0.30 and 21.0 mGy for a 10-year-old with 80 kVp, 10 mAs, and 0.8 second and with 140 kVp, 160 mAs, and 0.8 second, respectively). The volumetric anthropomorphic CT dose index for newborn phantoms was twice that for adult phantoms acquired similarly. The rod source dose was 0.03 mGy (3-minute scan). Although CT noise varied substantially among acquisition parameters, its contribution to PET noise was minimal and yielded only a 2% variation in PET noise. In a pediatric phantom, PET images generated by using CT performed with 80 kVp and 5 mAs for attenuation correction were visually indistinguishable from those generated by using CT performed with 140 kVp and 128 mAs. With very-low-dose CT (80 kVp, 5 mAs) for the adult phantom, undercorrection of the PET data resulted.For pediatric patients, adequate attenuation correction can be obtained with very-low-dose CT (80 kVp, 5 mAs, 1.5:1 pitch), and such correction leads to a 100-fold dose reduction relative to diagnostic CT. For adults undergoing CT with 5 mAs and 1.5:1 pitch, the tube voltage needs to be increased to 120 kVp to prevent undercorrection.

In micro-SPECT imaging, it can be challenging to model accurately the peripheral regions of a pinhole's response function, which correspond to large photon angles of incidence on the pinhole aperture. While it is possible, in principle, to simulate pinhole penetration and scatter accurately, uncertainties in the exact shape of the manufactured pinhole profile, or in detector sag angles during a SPECT orbit are problematic, especially for multi-pinhole systems where inconsistencies among projections can cause high-contrast streak artifacts in reconstructed images. We developed a method to reduce such artifacts, and tested it with data acquired on the Harvard Medical School muSPECT scanner. In this approach, we pre-calculate a set of rolled-off two-dimensional projection masks, one for each detector at each gantry angular position; during iterative reconstruction, the estimated and measured projections are both multiplied by the appropriate mask, which greatly reduces the magnitude of inconsistencies near the axial extrema of the pinhole projections. To compute the masks, we simulate by ray-tracing two sets of projection data from a uniform cylindrical emitter that fills the reconstruction field-of- view. The first set is simulated using the nominal pinhole maximum opening angle (73.6 degrees for our system); the second assumes the same opening angle, but the probability of each ray-traced photon path is weighted by a Hanning-window factor which decreases smoothly from unity (for all paths with angles of incidence within an opening angle less than 53.6-deg) to zero at 73.6-deg. The masks are then calculated by dividing the second set of simulated projections by the first. When this method was used to reconstruct measured high-count projections from Tc-99m phantoms, the streak artifacts were greatly reduced with no apparent loss of axial spatial resolution. Weighted reconstruction of Hanning-windowed projections is an effective approach for artifact reduction in muSPECT imaging.

Small-animal imaging is rapidly becoming an essential tool for preclinical development of new compounds for imaging and therapy. Although imaging performance evaluations and regular quality control are both important, surprisingly, there are relatively few appropriate phantoms available for such procedures. Phantoms can also be used with liquid or gel dosimeters for measuring radiation doses in different compartments, as well as cross-doses to other compartments. Both imaging and therapy applications, however, could benefit from phantoms with walls that are thinner than those currently available (~1 mm). Using high-resolution stereolithography (SL), we produced phantoms with 2-cm-long cold rods or hot channels ranging from 0.5 to 1.0 mm in diameter. Hollow spheres with 3- mm inner diameter were also produced, with wall thickness from 100 to 350 mum. All phantoms were imaged by muCT, with 27 mum resolution. SL performance was estimated by measuring the dimensions of many structures in the micro-CT images. We also evaluated the degree of water absorption by two different SL resins, Somosreg 11120 and Accurareg 40, after curing. The average bias (and precision) of the cold-rod and hot-channel structures over the size range 0.5 to 1.0 mm, were 0.75% (1.93%) and 0.9% (1.92%), respectively. Water absorption by the resins after 4 hours was minimal (0.1 to 0.15% weight change) for both materials; however, after 66 hours in water, the change was greater for Accurareg 40 (1.5%) than for Somosreg 11120 (0.25%); thus, the latter is a more suitable material for nuclear medicine applications. The muCT images demonstrated that the minimum acceptable spherical wall thickness was ~150 mum; this will allow beta particles from low-energy beta emitters, e.g., Lu-177, Cu-67, or 1-131, to deliver a greater radiation dose to neighboring compartments. SL is a robust and accurate method for fabrication of phantoms with thin walls for small-animal imaging systems and dosimetry measurements.

We have generalized the spectral factor analysis and the factor analysis of dynamic sequences (FADS) in SPECT imaging to a five-dimensional general factor analysis model (5D-GFA), where the five dimensions are the three spatial dimensions, photon energy, and time. The generalized model yields a significant advantage in terms of the ratio of the number of equations to that of unknowns in the factor analysis problem in dynamic SPECT studies. We solved the 5D model using a least-squares approach. In addition to the traditional non-negativity constraints, we constrained the solution using a priori knowledge of both time and energy, assuming that primary factors (spectra) are Gaussian-shaped with full-width at half-maximum equal to gamma camera energy resolution. 5D-GFA was validated in a simultaneous pre-/post-synaptic dual isotope dynamic phantom study where {sup 99m}Tc and {sup 123}I activities were used to model early Parkinson disease studies. 5D-GFA was also applied to simultaneous perfusion/dopamine transporter (DAT) dynamic SPECT in rhesus monkeys. In the striatal phantom, 5D-GFA yielded significantly more accurate and precise estimates of both primary {sup 99m}Tc (bias=6.4%{+-}4.3%) and {sup 123}I (-1.7%{+-}6.9%) time activity curves (TAC) compared to conventional FADS (biases=15.5%{+-}10.6% in {sup 99m}Tc and 8.3%{+-}12.7% in {sup 123}I, p

We assessed improvements in performance in detection and estimation tasks due to a novel brain single photon computed tomography collimator. Data were acquired on the CeraSPECT scanner using both new and standard collimators. The new variable focusing collimator SensOgrade samples the projections unequally, with central regions more heavily represented, to compensate for attenuation of counts from central brain structures. Furthermore, it utilizes more of the cylindrical crystal surface. Two phantom studies were performed. The first phantom was a 21-cm-diameter cylindrical background containing nine spheres ranging from 0.5 to 5 cm3 in volume. 99mTc sphere to background activity ratio was 10:1. Twenty-nine 10-min datasets were acquired with each collimator. The second phantom was the Radiology Support Devices (Long Beach, CA) striatal phantom with striatal-background ratios of 10:1 on the left and 5:1 on the right. Twenty-nine 4-min datasets were acquired with each collimator. Perfusion imaging using 99mTc-HMPAO was also performed in three healthy volunteers using both collimators under identical simulations. Projections were reconstructed by filtered backprojection with an unwindowed ramp filter. The nonprewhitening matched filter signal-to-noise ratio (NPW-SNR) was computed as a surrogate for human performance in detecting spherical lesions. Sphere activity concentration, radius, and location coordinates were simultaneously estimated by fitting images to an assumed model using an iterative nonlinear algorithm. Resolution recovery was implicit in the estimation procedure, as the point spread function was incorporated into the model. NPW-SNR for sphere detection was 1.5 to 2 times greater with the new collimator; for the striatal phantom the improvement in SNR was 54%. The SNR for estimating sphere activity concentration improved by 46 to 89% for spheres located more than 5 cm from the phantom center. Images acquired with the standard collimator were too noisy in the central regions to allow estimation of sphere activity. In 99mTc-HMPAO human studies, SNR was improved by 21 to 41% in the cortex, 66% in the basal ganglia, and 74% in the thalamus. The new collimator leads to substantially improved detection and estimation performance throughout the brain. The higher sensitivity will be particularly important for dynamic imaging.

We have developed a fast Monte Carlo (MC)-based joint ordered-subset expectation maximization (JOSEM) iterative reconstruction algorithm, MC-JOSEM. A phantom was scanned with CT and SPECT to compare quantitative imaging performance of MC-JOSEM with that of a triple-energy-window method (TEW) in which estimated scatter was also included additively within JOSEM, TEW-JOSEM. We acquired very-high-count projections of three 5.5-cc spheres of 111In taped in different locations in a water-filled torso/spine/lung phantom; 14 scans were then obtained with 111In only in the background for generating synthetic images of spheres in background. MC scatter estimates, which were used by MC-JOSEM, were computed once after 5 iterations (60 projections, 10 subsets) of TEW-JOSEM. Images after 36 iterations of both TEW-JOSEM and MC-JOSEM were obtained and counts were measured within volumes-of-interest centered on the spheres in all sphere+ background and background-only image sets. The bias ranged from 7.7% to 14.1% for TEW-JOSEM, and from 8.9% to 11.3% for MC-JOSEM, while the precision was significantly better for MC-JOSEM (5.4% to 11.2%) than for TEW-JOSEM (9.2% to 17.9%). MC-JOSEM is a promising approach for quantitative SPECT.

At neutral pH, metal radionuclides, e.g., In-111 and Y-90, precipitate and adhere to container walls, yielding nonuniform activity distributions in compartments of plastic phantoms used for dosimetry validation. For various concentrations of a chelator, EDTA, we evaluated the uniformity of activity distributions in phantoms, as well as the accuracy of a fluorescent liquid dosimeter, coumarin-3-carboxylic acid (CCA). Solutions of In-111 and Y-90 with activity concentrations of 10-25 μCi/cc containing increasing EDTA concentrations (0-25 μM) were stored in polymethyl methacrylate (PMMA) phantoms for 24 h to accumulate dose. Activity in the solution was then measured in a gamma counter and/or by μSPECT imaging. Phantoms containing 0.1 mM CCA with EDTA were also irradiated either with a Cs-137 irradiator or with Y-90 to evaluate the effect of EDTA concentration on fluorescence intensity (FI). Activity measurements from images and gamma counting indicated that 40-50% of the activity of In-111 and Y-90 (25 μCi/cc) accumulated on phantom walls for EDTA concentration 2.5 μM. For a fixed absorbed dose, fluorescence intensity decreased by

A 70 cm long polyethylene cylinder of radius 10 cm containing an off-center line source has been suggested for the characterization of PET tomograph whole-body performance in terms of scatter fraction, sensitivity to randoms and count-rate capability. In this work we perform a series of Monte Carlo simulations of a full-ring BGO system operating in 3D mode and a full-ring sodium iodide system operating in 3D mode to determine how closely scatter fraction and NEC results from the 70 cm cylinder follow those found in anthropomorphic activity and attenuation distributions. We find that the 70 cm cylinder measurements correctly rank-order the tomographs in terms of scatter fraction and NEC performance, but do not always accurately predict the actual scatter fractions or the peak NEC values encountered in the anthropomorphic models. Peak NEC for the phantom occurs at around double the activity concentrations which give rise to peak NEC in the anthropomorphic objects.

Simultaneous dual isotope imaging (Tc-99m/I-123) has potential clinical applications but has not been implemented in the clinic. The aim of this work was to optimize the design of an artificial neural network (ANN) for cross-talk and scatter correction using a smaller number of energy windows (8) than we had previously proposed (26) to allow implementation on some clinical cameras, and to validate our approach using realistic Monte Carlo simulations and anthropomorphic brain phantom acquisitions. Monte Carlo simulations of dual isotope SPECT studies of a digital brain phantom and physical acquisitions of the striatal brain phantom were used to validate our approach. Corrected projections were reconstructed using an iterative OSEM algorithm that modeled non-uniform attenuation and variable collimator response in the projector/backprojector. In simulated I-123 images, ANN26 and ANN8 yielded similarly accurate (bias

SPECT imaging with isotopes other than /sup 99m/Tc is useful for developing new molecular probes for in-vivo imaging. We have recently modified a standard 3-head gamma camera system for /spl mu/SPECT with 6 pinhole tungsten collimators using a 3D-OSEM reconstruction algorithm. We have previously reported on the /sup 99m/Tc performance of this /spl mu/SPECT imager. We have recently measured the performance of the /spl mu/SPECT system for imaging with /sup 125/I, /sup 123/I, and /sup 111/In. The smallest of the interchangeable apertures (0.8-mm) was used for all tests. Point sources consisted of droplets or ion exchange beads with /sup 123/I and /sup 111/In. The imaging of /sup 125/I was simulated using the 30-keV X-rays from /sup 123/I. The volume source was a 30 cc syringe containing 25 ml. Point and volume projection data were acquired separately. The projection data sets of point and volumes were scaled and added before reconstruction. The pinhole-collimated /sup 123/I energy spectrum demonstrated 18% contribution from high-energy photons detected in the 159-keV, 20% wide window, whereas a low-energy parallel-hole collimator allowed 60% contamination. The point-source sensitivity at 159 keV was comparable to that measured previously for /sup 99m/Tc (18 cpm/kBq), and was 3.6 times higher than that measured in the X-ray region (30-keV, 50% window). Point sensitivity for /sup 111/In was 39 cpm/kBq. Volume sensitivities were 1.4 cpm/kBq at 30 keV, 4.3 cpm/kBq at 159 keV and 14 cpm/kBq for /sup 111/In. With 1 iteration, the average FWHM resolution at 30 keV was 1.05 mm, at a background noise level of 40%. Average resolution for /sup 123/I and /sup 111/In were both measured to be 1.2 mm at a 10% noise level with 1 iteration and decreased to 0.9 mm at 25% noise level and 3 iterations. The /spl mu/SPECT system performs comparably for /sup 99m/Tc, /sup 123/I and /sup 111/In and acceptably for /sup 125/I. New iodinated probes and mice containing /sup 111/In are now being imaged with the system.

Improved Indium-111 SPECT imaging should lead to better dose specification in radiotherapy treatment planning; however, photon scatter and down-scatter from the 245- to the 171-keV photopeak represent significant challenges for quantitative SPECT. We have extended to /sup 111/In a general-spectral (GS) scatter-compensation method. List-mode acquisitions of a 1.6-cm-diam. sphere containing /sup 111/In were obtained with the sphere in three different locations on the major axis of a water-filled elliptical cylinder. The sphere was then removed, the phantom was injected with /sup 111/In, repositioned, and scanned repeatedly. High-count, list-mode data from separate sphere and background scans were rebinned into 10-keV windows from 100-280 keV. Attenuated projections, free of scatter and noise, were simulated for use in a least-squares procedure to optimize GS coefficients for a sphere activity-estimation task. Scattered photons in both photopeaks were estimated separately from synthetic noisy projections under different conditions of activity contrast and sphere location; projections were reconstructed with our joint, multi-energy OSEM program. The bias of sphere activity values estimated from projections was less than 7% for both photopeaks and for all contrast values ranging from 2:1 to 8:1; the bias (precision) of sphere activity estimated from OSEM reconstructions was less than 8.5% (3%) for all sphere positions. The GS compensation method is a promising approach for quantitative /sup 111/In SPECT.

Because of increasing interest in patient-image-based dosimetry, dosimetry validation in phantoms would be useful, particularly for modeling complex source-target geometries. We have devised a fluorescence technique to measure doses to liquid-filled compartments. Solutions containing 0.1 mM coumarin-3-carboxylic acid (CCA) with Y-90 (YA) and without Y-90 (NA) were prepared. We measured the self-absorbed dose in six spheres, three cylinders, and two shell-sphere geometries. Each shell-sphere geometry consisted of an inner sphere containing NA solution, surrounded by an outer shell containing YA solution. This enabled us to measure the self-dose to the source shell as well as the cross-dose to the target sphere. After a 24 or 48 hour exposure, the mean dose to each compartment was estimated by measurement of the induced fluorescence in the solutions. A calibration curve obtained using NA solution exposed in a Cs-137 irradiator (98.3 rads/min) for different times displayed a linear increase in fluorescence with increasing dose up to 1500 rads. The self-dose increased with sphere or cylinder size, and agreed within plusmn8.5% with values computed using a Y-90 dose point-kernel method. However, the dose delivered to the 'cold' sphere compartment from the adjacent 'hot' shell, which was a few percent of the self-dose to the hot compartment, showed a large discrepancy between measured and calculated values. CCA fluorescence dosimetry is a promising technique for verification of dose calculations

We have quantified resolution and contrast loss as a function of noise-equivalent count rate on the GSO-based Philips Allegro and the pixelated NaI CPET2 using previously developed methodology involving the NEMA NU 2-2001 70 cm test phantom and a Na-22 point source. We found that at peak NEC, neither system showed significant loss of resolution. However, after accounting for event loss due to dead time, loss of contrast was seen in both systems.

Most current PET detector designs suffer from event mispositioning at high count rates, as scintillation light from nearby and nearly simultaneous gamma ray conversions becomes mixed. We have used the NEMA NU 2-2001 70 cm test phantom and a Na-22 point source to quantify this effect as a function of activity on two block-detector tomographs (the Siemens/CTI HR+ and the General Electric Discovery LS), and two Anger-type PET tomographs (the Siemens ECAM DUET and the Philips CPET+). After accounting for event losses due to dead time, we find that the number of counts on LORs passing through a cylinder of diameter and height equal to the point-source full width at tenth-maximum measured at low rate surrounding the point source decreases by between 9% (HR+) and 35% (CPET+) at the activity giving rise to peak noise equivalent count (NEC) rate. Mispositioned events act to reduce signal-to-noise ratio, both by reducing apparent activity at the originating location and by increasing the signal background. We have reformulated the conventional expression for NEC rate to account for this phenomenon. The new formulation of NEC, which we call NEC/sup */, results in a lower peak value which in turn occurs at a lower activity concentration than for the conventional formulation.

Standard nuclear medicine imaging uses photon collimation and thus suffers from very low sensitivity, especially if high energy (>511 keV) isotopes are to be imaged. Coded aperture techniques use a coded pattern mask instead of a collimator to encode the photon source distribution, thus every photon source contributes to the signal in the whole detector area. It significantly improves the system sensitivity while retaining the spatial resolution of the reconstructed images. The authors have developed coded aperture arrays which are specifically designed for near field imaging, rather than the far field imaging appropriate to X-ray astronomy and have placed an emphasis on reducing sidelobe response in order to increase utility for images with background. The authors have used a cyclic difference set uniformly redundant array as the coded aperture pattern; have conducted imaging experiments for point sources, 2-D sources (sources in a plane with arbitrary distribution), and 3-D sources (sources in 3-D with arbitrary distribution) of 511 keV through phantoms; and have compared the experimental results with those from collimator systems. The coded aperture experiments have been conducted using a Siemens E.CAM gamma/SPECT camera. Results from the authors' experiments show significantly improved sensitivity for a coded aperture imaging system over collimator systems, while retaining reasonable resolution. The authors have demonstrated the possibility of using coded apertures and a conventional gamma camera to image gamma rays of high energy, such as 511 keV, in nuclear medicine.

The authors estimated the detectability of spheres of different sizes but equal activity contrast, embedded in a clinically realistic phantom in order to compare two-dimensional (2D) and three-dimensional (3D) whole-body (WB) PET imaging for a relevant diagnostic task. Five plastic spheres with inside diameters of 0.8 to 3.4 cm, containing 74 kBq/ml of Ge-68, were placed in an anthropomorphic torso phantom. The background organs contained F-18 activity concentrations in appropriate physiologic proportions, as did a head phantom positioned outside the field of view (FOV) of the authors' ECAT-HR+ system. The phantom was scanned for 9 hours at 1 bed position as the F-18 decayed from 97 to 3.2 kBq/ml. The authors obtained 10, 1-minute scans for each activity contrast level, alternating among 3 acquisitions: 2D mode with standard maximum ring difference (MRD=7), standard 3D mode (MRD=22), and 3D mode with MRD=13 (3D*). Images from 2D and 3D acquisitions were reconstructed by filtered backprojection and 3D reprojection (3DRP); 3D data were also reconstructed by FBP after Fourier rebinning (FORE+FBP). Sphere detectability was estimated using non-prewhitening (NPW) matched filtering to compute the detection signal-to-noise ratio, NPW SNR. In almost all cases, NPW-SNR was greater for 3D or 3D* than for 2D, although 2D outperformed 3D with 3DRP reconstruction at the earliest time points for 2 spheres located near opposite ends of the axial FOV; FORE+FBP reconstruction significantly improved the detectability of these spheres, compared to 3DRP, and demonstrated the expected near equivalence of 3D and 3D* data from spheres near the ends of the FOV. The authors' results were not predictable from global NEC considerations alone.

Coded aperture techniques based on a cyclic difference set uniformly redundant array (URA) can increase sensitivity of an imaging system without degrading the spatial resolution. In this paper, we discuss the pattern design and present its application for diagnostic nuclear medicine imaging with experimental results. Point-like, planar, and three- dimensional 140 keV gamma-ray sources are used in our experiments. We have experimentally demonstrated a three- dimensional coded aperture technique for nuclear medicine imaging and have compared it with conventional collimator systems.

The dopamine transporter (DAT), located presynaptically on dopamine neurons, provides a marker for certain neurological diseases. In particular, the DAT is depleted in Parkinson's disease, and the extent of depletion correlates with the loss of dopamine. Herein we describe the design, synthesis, and biological evaluation of technepine, the first 99mTc-labeled SPECT imaging agent which targets the dopamine transporter in striatum. We have demonstrated that the DAT can accommodate a chelating unit attached to the 8-amine function of a tropane skeleton. Further, we have demonstrated for the first time that a molecule can be designed to carry the radionuclide 99mTc across the blood−brain barrier in sufficient quantity to obtain in vivo images of the striatum in monkeys. This advance will undoubtedly lead to the design of new receptor and transporter-mediated 99mTc agents which can label specific transporter and receptor targets in the central nervous system.

In some instances patients present with thyroid cancer that does not seem to fit the usual treatment guidelines as set forth in conventional texts. For example, there may be an unusual distribution of thyroid remnants or metastases or there sometimes are extensive metastases to the lung or other organs. In these cases knowledge about regional uptake of therapeutic Iodine 131 (131I) is useful.

Magnification is an indispensable technique in pediatric nuclear medicine that is used to improve the relatively low resolution characteristics of gamma cameras typically equipped with parallel hole collimators. Magnification scintigraphy is useful for the assessment of diseases of the thyroid, kidney, heart, small bones, and scrotum.2,4–7,10 To achieve magnification the usual parallel hole collimator is replaced by a pinhole collimator or possibly a converging collimator.

✓ Deteriorating clinical status after high-dose radiation therapy for high-grade gliomas may be due to radiation changes or may signal recurrent or residual tumor mass. The two conditions cannot be distinguished reliably by computerized tomography (CT) or magnetic resonance (MR) imaging. The authors assessed the ability of sequential thallium-201 chloride (201T1) and technetium-99m hexamethylpropylene amine oxime (99mTc HMPAO) single-photon emission CT (SPECT) to distinguish tumor recurrence from radiation changes after high-dose (≥ 600 cGy) radiation therapy for malignant gliomas. Preoperative tumor/nontumor uptake ratios were analyzed in 32 patients and correlated with the presence of gross tumor at the time of reoperation. In 12 of 13 patients with 201T1 tumor/scalp ratios of 3.5 or greater, recurrent tumor was present. The authors found 99mTc HMPAO SPECT to be useful for identifying the absence of solid tumor recurrence in patients with low to moderate 201T1 uptake (ratio 1.1 to 3.4) and low perfusion to that site. In 11 of 12 patients with 99mTc HMPAO tumor/cerebellum ratios of 0.50 or less, no recurrent tumor mass was present. Three of seven patients with 201T1 ratios of 3.4 or less and 99mTc HMPAO ratios of 0.51 or more had recurrent tumor found at surgery; thus the test was not predictive in this group. It is concluded that the use of sequential 201T1 and 99mTc HMPAO SPECT accurately identifies the presence of tumor recurrence versus radiation changes in most patients with high-grade astrocytomas who have undergone tumor resection and high-dose radiation therapy.

99mTc-L,L-Ethyl cysteinate dimer (ECD) is a brain-perfusion imaging agent, which exhibits selective retention in brain and rapid renal excretion. The pharmacokinetics and metabolism of ECD were studied in vivo in healthy humans and its metabolism in vitro was evaluated in tissue from human brain. In vitro studies showed 99mTc-L,L-ECD to be metabolized to a polar 99mTc-complex. It has been shown previously that most of the activity of 99mTc retained in the brain of the monkey in vivo is in the form of a polar 99mTc complex (Walovitch, Hill, Garrity, Cheesman, Burgess, O'Leary, Watson, Ganey, Morgan and Williams, 1989). Whole body images of the distribution of 99mTc-L,L-ECD (10 mCi i.v.) in four adult males showed good uptake in brain, with slow elimination (6.8 +/- 0.3% injected dose [mean +/- SE] at 5 min), with less than 25% decrease in activity during 4 hr of imaging. Background areas in the head and lungs washed out rapidly, providing ideal imaging conditions. Elimination of 99mTc from venous blood was biphasic, with a plateau of activity between 2-15 min (7-8% injected dose) before a terminal phase, with a t1/2 of a few hours. Organic extraction of whole venous blood showed greater than 50% of the 99mTc-L,L-ECD to be in the form of polar metabolite(s) at 5 min. They were identified in the urine as the 99mTc ethylenediylbis-L-cysteine, monoethyl ester complex (ECM) and the 99mTc-ethylenediylbis-L-cysteine complex (EC). These metabolites were excreted rapidly (75% injected dose in urine within 6 hr). The results of this study support the hypothesis that the selective retention in brain, rapid blood elimination and renal excretion of 99mTc-L,L-ECD is due to its metabolic transformation to polar end products.

The geometric component of the point spread function (PSF) of a gamma camera collimator can be determined analytically, and the penetration component can be calculated readily by numerical ray-tracing. A Monte Carlo simulation of photon transport which includes collimator scatter is developed. The simulation was implemented with an array processor which propagates up to 1024 photons in parallel, allowing accurate estimates of the total radial PSF in less than a day. The simulation was tested by imaging monoenergetic point sources of Tc-99m, Cr-51, and Sr-85 (140, 320, and 514 keV, respectively) on a General Electric Star Cam with low-energy, general-purpose, and medium-energy collimators. Comparisons of measured and simulated PSFs demonstrate the validity of the model and the significance of collimator scatter in the degradation of image quality. >

To identify group differences in the prodromal phase of Alzheimer disease (AD) using quantitative single-photon emission computed tomography (SPECT) perfusion and magnetic resonance imaging (MRI) volume measures within specific volumes of interest.Gerontology research unit.There were 17 healthy controls, 56 nondemented patients with memory problems who did not develop AD during 3 to 5 years of follow-up (questionables), and 27 nondemented patients with memory problems who developed AD during follow-up (converters).A Tc 99m hexamethylpropyleneamine oxime SPECT study and an MRI were performed in each participant at baseline. Mean SPECT activity concentration and MRI volume were estimated within 9 structures: rostral anterior cingulate, caudal anterior cingulate, posterior cingulate, hippocampus, entorhinal cortex, basal forebrain, temporal horn, amygdala, and the banks of the superior temporal sulcus. Data were analyzed using overall and pairwise discriminant analysis, and performance in pairwise group discrimination was measured using correlated receiver operating characteristic curve analysis.The overall (3-group) discriminant function was significant for SPECT (F test, P.001) and MRI (F test, P.0001). For the SPECT analysis, the ranking of structures for discriminating among the 3 groups was, in order of decreasing discriminating power, caudal anterior cingulate, temporal horn, superior temporal sulcus, entorhinal cortex, hippocampus, rostral anterior cingulate, amygdala, basal forebrain, and posterior cingulate. For the MRI analysis, this ranking was entorhinal cortex, superior temporal sulcus, temporal horn, hippocampus, amygdala, caudal anterior cingulate, rostral anterior cingulate, basal forebrain, and posterior cingulate. Combining the 2 modalities yielded significantly better discrimination performance than did either alone. Furthermore, the correlation between SPECT and MRI measures was low.Measures of structure activity concentration and volume carry independent information; both reveal group differences in prodromal AD.

Thirty-six (36) spinal cord injury patients (22 tetraplegic and 14 paraplegic) had hand radiographs taken in association with bone density measurements. The cortical bone of the hand, the radius, and the ulna was found to be normal, but there was an obvious decrease in the amount of trabecular bone. There were three predominant radiographic patterns of osteopenia --generalised, juxta-articular, and cystic. The cause of this decrease in trabecular bone is not understood, although it may be related to alterations in blood flow.

The detection efficiency of a high‐pressure, gas scintillation proportional chamber (GSPC), designed for medical imaging in the 30–150 keV energy range, has been investigated through measurement and Monte Carlo simulation. Measurements were conducted on a GSPC containing 4 atm of pure xenon separated from a hexagonal array of seven ultraviolet‐sensitive photomultiplier tubes by 1.27‐cm‐thick fused‐silica windows. Experimental measurements of the photopeak efficiency, fluorescence escape efficiency, and the energy collection efficiency were obtained. Results were also obtained for different photon energies and different values of temporal resolution. The measurements were compared with the results obtained from a Monte Carlo simulation designed specifically for investigating the imaging of low‐energy photons (below 150 keV) with a gas‐filled detector. The simulation was used to estimate photopeak efficiency, fluorescence escape efficiency, photopeak‐to‐fluorescence escape peak ratio, quantum interaction efficiency, energy collection efficiency, and local energy collection efficiency. The photopeak efficiency of the GSPC relative to that of a 3‐in. (7.62‐cm)‐thick sodium iodide crystal was measured to be 0.284±0.001 at 60 keV and 0.057±0.001 at 140 keV. Of the 60‐keV photons incident upon the detector, 70%±4% interacted in the detector, with 28%±1% being in the photopeak, as estimated both by experimentation and through the simulation. The maximum energy collection efficiency was found to be 65% at 60 keV, with 46% being deposited within 0.2 cm of the initial photon interaction. The information gained from this study is being used to design an optimized detector for use in specialized nuclear medicine studies.

The mesh chamber consists of a multi-layer tungsten mesh gamma convertor coupled to a multiwire proportional chamber. Spatial resolution, time resolution, and efficiency will be discussed for such detectors as applied to positron emission imaging systems operating in both an area and slice mode.

In radiation therapy of patients with breast carcinoma, the ipsilateral internal mammary lymph nodes are either irradiated by a separate anterior field or included by isocentric opposing tangential fields, which also treat the breast and chest wall. To determine the acceptability of a particular treatment setup, the positions of the nodes must be determined with respect to the treatment fields. For the anterior field technique the problem is two-dimensional and is solved by simply superimposing the treatment field onto an anterior lymphoscintigram. For treatment by opposing tangential fields the problem is three-dimensional and more complex. The solution described in this note is to project the three-dimensional lymph node positions, obtained by a stereo-lymphoscintigraphic procedure, onto the tangential field radiographs. A mathematical expression is given to perform the required projection of the node positions onto the radiographs.

With an Anger camera for scintigraphic recording of bremsstrahlung radiation from phosphorus-32, the distribution of intraperitoneal colloidal chromic phosphate was followed in patients with gynecologic tumors. Sequential pelvic, abdominal, and thoracic scintiphotos over a three-week period revealed rapid and persistent focal aggregation of the radiocolloid with no change in pelvic or peritoneal radionuclide distribution patterns. Visualization of intrathoracic lymph node uptake did not correlate with the presence of diaphragmatic tumor. This study demonstrates the utility of scintigraphy for monitoring the distribution of intraperitoneal beta emitters and the need for developing alternative methods of administering these therapeutic agents to achieve more uniform patterns of distribution.

Several different classes of chemical carcinogens induced the transformation of human fibroblasts grown in vitro. Characteristics of the events that occur from time of treatment through the expression of neoplastic transformation are presented. The S-phase appeared to be the portion of the cell cycle most vulnerable to insult. Staging of the cells by blocking them in G1 before releasing them to proceed through scheduled DNA synthesis (S) was required to induce reproducible transformation. Compounds such as insulin were added to the cells upon release from the block to sensitize the cells to the carcinogen that was added during S. Growth of the transformed cells as distinct from nontransformed cells was promoted by growth in medium supplemented with 8X nonessential amino acids. Carcinogen-treated cells in the early stage of transformation exhibited abnormal colony morphology and were able to grow at 41 degrees C, in air atmosphere, and in medium supplemented with only 1% serum. In addition, the transformed cells were insensitive to KB cell lysate and exhibited density independent, as well as anchorage independent, growth (i.e., growth in 0.33% agar). Cells that grew in soft agar also produced undifferentiated mesenchymal tumors in preirradiated nude mice.

A pressurized multiwire proportional chamber radionuclide imaging system has been constructed which has operated at pressures of up to 11 atmospheres absolute using a xenon-methane gas mix. The experimental detector has an active imaging area of 25 sq. cm. and an effective depth of 11 cm. An all digital readout system has been constructed with an intrinsic resolution of 1.3 mm FWHM. The FWHM has been measured for various radionuclides: iodine-125 (28 keV), 1.3 mm; thallium - 201 (75 keV), 2 mm; technetium-99 m (140 keV), 3 mm. Our primary goal has been the investigation of properties of such detectors that offer advantages over conventional gamma cameras, including high data rate and improved spatial resolution, particularly for isotopes with photon energies below 100 keV. We have fabricated a gas purification system which permits long term operation of the system without degradation and have investigated construction techniques to produce reliable devices which could be used in a hospital environment.

Photon absorptiometry provides an accurate measurement of bone mineral content. In acromegaly, the bone mineral content is normal, whereas the bone mineral content is reduced by acidosis. Decreased bone mineral content occurs in alcoholics due to osteomalacia and also in anticonvulsant therapy for the same reason. In hyperparathyroidism, there is decreased bone mineral content. Corticosteroids reduce bone mineral content especially in the central skeleton similar to Cushing's disease. Glutethimide causes osteomalacia with decreased bone mineral content. Long-term heparin therapy causes bone resorption. Immobilization causes decreased bone mineral content. Bedrest and space flight reduce lower limb bone mineral content with recovery on ambulation. Conversely, activity increases bone mineral content even in the elderly and bone mineral content is greater in athletes than non-athletes. Osteoporosis is a normal process occurring from age 45 years in females and 65 in males. Bone loss is related to menopause and lactation in females and may be arrested by estrogens, fluoride (with calcium and vitamin D), and possibly calcium carbonate. Decreased bone mineral content occurs at all stages of renal failure with rapid bone mineral content loss in azotemia and during dialysis and slower loss after transplant. Parathyroidectomy does not affect bone mineral content in renal osteodystrophy. The bone mineral content is normal in compact bone but decreased in trabecular bone in patients with spinal cord injury, as well as in leprosy and diabetes. In hemiplegia, there is decreased bone mineral content on the paralyzed side. In thyrotoxicosis, there is increased formation and resorption of bone.

We have constructed a large area (25 cm diameter), pressurized (4 atmosphere) xenon-helium gas scintillator for imaging shortlived isotopes in the 60 - 80 keV range. The scintillator is viewed by an array of quartz windowed PMT's arranged in a simple Anger type readout. The energy and time resolution have been measured for various mixtures of xenon-helium. For Xe-133 (81 keV), an energy resolution of 6% FWHM has been obtained. The light output of the detector is a Gaussian shaped pulse with a width of 2 ?s at the base. Spatial resolution has been measured at 3 - 4 mm FWHM. The physical limitations of the detector as well as design changes which will improve energy and spatial resolution are discussed. These improvements should permit the development of imaging detectors with simultaneous high rate and high energy resolution for applications such as first-pass studies with shortlived isotopes or imaging of low energy isotopes where contrast is reduced by scatter.

A high‐pressure gas scintillation proportional chamber has been designed and constructed to image x and gamma rays for medical applications. The chamber contains 4 atm of pure xenon. Ultraviolet light emitted from excited xenon atoms within the detector is collected by a hexagonal array of seven UV‐sensitive photomultiplier tubes, which in turn are separated from the pressurized gas by 1‐cm‐thick fused‐silica windows. A model was used to predict the energy resolution of the device as a function of fill‐gas pressure, voltage within the detector, and light‐collection efficiency. The energy resolution improved with increasing scintillation region voltage from 17% full width at half maximum (FWHM) at 1.9 kV to 10% FWHM at 3.0 kV for 59.5‐keV photons; once above 1.5 kV, there was no improvement with increasing drift voltage. The addition of the signals from the peripheral phototubes to that of the center phototube did not substantially improve the energy resolution of the device. This was because the noise that was present yielded a high correlation between the phototubes; when this noise was incorporated into the model, the energy resolution of the multiphototube system was accurately estimated. The energy resolution of the gas scintillation proportional chamber was found to be superior to the sodium iodide Anger camera at 59.5 keV by a factor of 2. Further improvement can be obtained by increasing the scintillation region voltage and by increasing the light‐collection efficiency by moving the scintillation region closer to the phototubes.