ADAPTIVE SMALL-ANIMAL SPECT/CT.

We are exploring the concept of adaptive multimodality imaging, a form of non-linear optimization where the imaging configuration is automatically adjusted in response to the object. Preliminary studies suggest that substantial improvement in objective, task-based measures of image quality can result. We describe here our work to add motorized adjustment capabilities and a matching CT to our existing FastSPECT II system to form an adaptive small-animal SPECT/CT.

Tomographic Small-Animal Imaging Using a High-Resolution Semiconductor Camera.

We have developed a high-resolution, compact semiconductor camera for nuclear medicine applications. The modular unit has been used to obtain tomographic images of phantoms and mice. The system consists of a 64 x 64 CdZnTe detector array and a parallel-hole tungsten collimator mounted inside a 17 cm x 5.3 cm x 3.7 cm tungsten-aluminum housing. The detector is a 2.5 cm x 2.5 cm x 0.15 cm slab of CdZnTe connected to a 64 x 64 multiplexer readout via indium-bump bonding. The collimator is 7 mm thick, with a 0.38 mm pitch that matches the detector pixel pitch. We obtained a series of projections by rotating the object in front of the camera. The axis of rotation was vertical and about 1.5 cm away from the collimator face. Mouse holders were made out of acrylic plastic tubing to facilitate rotation and the administration of gas anesthetic. Acquisition times were varied from 60 sec to 90 sec per image for a total of 60 projections at an equal spacing of 6 degrees between projections. We present tomographic images of a line phantom and mouse bone scan and assess the properties of the system. The reconstructed images demonstrate spatial resolution on the order of 1-2 mm.

Intraoperative tumor detection: relative performance of single-element, dual-element, and imaging probes with various collimators.

Accurate tumor staging depends on finding all tumor sites, and curative surgery requires the removal of ail cancerous tissue from those sites. One technique for locating tumors is to inject patients before surgery with a radiotracer that is preferentially taken up by cancerous tissue. Then, an intraoperative gamma-sensitive probe is used to locate the tumors. Small (<1-cm diameter) tumors, often undetectable by external imaging and by the standard surgical inspection with sight and touch, can be found with probes, Simple calculations and measurements with radioactive tumor models show that small tumors should be detected by single-element probes, but often such probes fail to detect these small tumors in practice. This discrepancy is often caused by the use of a uniform background to predict probe performance, Real backgrounds are nonuniform and can decrease probe performance dramatically. Dual-element, coincidence, or imaging probes may solve the background problem. The authors devised a method to predict probe performance in a realistic background which includes variations in normal organ uptakes. They predict the relative performance of both existing probes and those in the design stage so that optimal detector and collimator configurations can be determined. The procedure includes a Monte-Carlo-calculated point-response function, a numerical torso phantom, and measured biodistributions of a monoclonal antibody. The Hotelling Trace Value, a measure of tumor-detection performance, is computed from the probe responses in simulated studies.

Comparison of NaI(Tl), CdTe, and HgI2 surgical probes: physical characterization.

The physical properties of three surgical probes containing different radiation detectors are compared: a NaI(Tl) scintillator with a flexible, fiber-optic light guide, and two semiconductor detectors that operate at room temperature, CdTe and HgI2. Also compared are spectra, energy resolutions, and counting efficiencies measured at a variety of gamma-ray energies between 30 and 1000 keV. The energy resolution of the NaI probe is substantially poorer than that of either semiconductor probe due in part to light losses in coupling the scintillator to the fiber optics. The semiconductor probes have complex spectral response due to charge-carrier trapping and K x-ray escape, and not all photoelectric interactions in these detectors contribute to the useful part of the photopeak. Above 120 keV the counting efficiency for the NaI probe is an order of magnitude higher than for the CdTe and HgI2 probes. Both energy resolution and counting efficiency are slightly better for the HgI2 probe than for the CdTe probe.

Comparison of NaI(T1), CdTe, and HgI2 surgical probes: effect of scatter compensation on probe performance.

Spatial variation in the background source distribution makes tumor detection difficult for single-detector probes. Using a single energy window that brackets the photopeak helps discriminate against background events dominated by Compton scattering. Another approach is to use the information provided by an additional window in the Compton region. The performances of NaI(T1), CdTe, and HgI2 surgical probes have been compared under realistic simulations of a tumor-staging procedure using optimal single-sided energy windows and a two-window scatter-subtraction technique. Results showed that despite the differences in energy resolution of the detectors, the performances of the probes in a variable background were similar when optimal single energy windows were used. When the background variations were large, using information provided by a second window improved probe performance.

Probability modelling of a surgical probe for tumour detection.

Probability functions for the output counts from a radiation detector probe are needed to implement Bayesian detection strategies or to assess performance of the probe. This paper presents methods for simulating a surgical probe designed for tumour detection to obtain statistical information for modelling probability functions of output data. Statistical models of pharmaceutical uptake in normal organs and tumours were estimated from animal and human data, and these models were combined with a digitised human torso phantom to create a large set of simulated patients. With the simulated patients and with a spatial map of the probe response, computer simulations of intraoperative probe measurements provided a large set of simulated probe data. Probability models derived from these data using maximum-likelihood methods helped to formulate the detection strategy and to evaluate the performance of the surgical probe.

Whole-body lymphangioscintigraphy: preferred method for initial assessment of the peripheral lymphatic system.

In 20 patients with congenital and acquired lymphedema in either upper or lower extremities and in four patients without extremity edema, human serum albumin labeled with technetium-99m was injected intradermally into a digital web space of the hand or foot. With a digital gamma camera that permitted a "sweep" of the torso, serial extremity and whole-body lymphagioscintigraphy (LAS) of the peripheral lymphatic system was performed. In 11 patients with acquired lymphedema, a well-defined obstructive pattern was seen, characterized by discrete peripheral lymphatic trunks, delayed or absent depiction of regional nodes, and delayed but extensive soft-tissue tracer extravasation. Five of nine patients with congenital lymphedema showed hypoplasia characterized by poorly defined lymphatic trunks, delayed depiction of regional nodes, and early and extensive extravasation of tracer. The other four patients showed aplasia, with absence of trunks, no depiction of nodes, and little or no tracer extravasation. LAS is technically simple to perform and requires no special training. Radiation exposure is minuscule, and the procedure is safe and without apparent side effects. For these reasons, whole-body LAS should be the preferred method for the initial assessment of congenital or acquired lymphedema.

Comparison of in vivo scintillation probes and gamma cameras for detection of small, deep tumours.

An in vivo probe was compared with a gamma camera for the task of detecting radiolabelled tumour models in a water phantom. The probe, which contained a 1 cm diameter NaI(T1) detector, was designed and used by us for surgical staging studies of gynaecological patients. Tumours were spherical sources of different sizes and activities per unit volume of cobalt-57. The phantom was a tank of water (451) containing dissolved radioactivity to simulate background activity. Detector-to-source separations and tank depths were also varied. Camera images of 10 min duration were compared with probe counts of 15 s. For each configuration a large number of source and background runs were analysed using an ideal-observer ROC technique. Area under the ROC curve was used as the figure of merit. Results show that for approximately uniform background the probe should perform substantially better than the gamma camera in detecting small, deep tumours provided that the probe can be manoeuvred to within a few centimetres of the tumour. Mathematical modelling of our results indicates that this conclusion is not dependent on radiopharmaceutical dose, tumour uptake or camera type.

A utility-based model for comparing the cost-effectiveness of diagnostic studies.

The effective cost of a diagnostic test is the money spent per unit of diagnostic performance. The latter can be measured as diagnostic utility (DU), the probability-weighted sum of the utilities of the four test outcomes TP, TN, FP, and FN: DU = U(TP)P(TP) + U(TN)P(TN) + U(FP)P(FP) + U(FN)P(FN). DU (which also is called expected utility) incorporates the clinical decision analytic variables sensitivity (Se), specificity (Sp), equivocal fraction (EF), disease probability (P(D)), and outcome utility (U). DU is not an inherent property of a diagnostic test but of test-observer interactions in a clinical setting. The model sets the effective cost (EC) of a diagnostic test = actual direct cost (ADC)/DU. When DU = 1 (perfect test) EC = ADC and the patient benefits from the test dollar for dollar. When DU less than 1, EC exceeds ADC. If DU approaches O, EC becomes infinite; the test has no effectiveness at any cost. DU depends strongly on P(D) if Se and Sp differ significantly; then EC also depends on P(D), and the effective cost of a test performed in the wrong P(D) setting may be several times its actual direct cost. This model of comparing effective costs compares actual direct cost with clinical measures of test performance and utility values that allow expression of patient/doctor fears and preferences. It offers a more clinically realistic setting than models based on costs alone.

Dual-detector probe for surgical tumor staging.

A hand-held, dual-detector probe has been developed for surgical tumor staging. This dual probe simultaneously monitors counts from a possible tumor site along with counts from adjacent normal tissue using two concentric, collimated scintillation detectors. A comparison of counts from the detectors can distinguish a small tumor directly in front of the probe from variations in background activity. The probe was tested in computer simulations of surgical staging of metastases to para-aortic and iliac lymph nodes using a spatial response map of the probe, a numerical torso phantom, and organ activity data for [57Co]bleomycin in rabbits. Results show that the dual probe performs better than a single-detector probe in detecting tumors and solves the problem caused by spatial variations in the background source distribution.

Detection of small radiation sources: the effect of mode of count-rate presentation.

We used an observer-performance study to compare four different modes of presenting count-rate data from a radiation detector. Observers searched for small, concealed radioactive sources using a hand-held radiation-detector probe. The modes of count-rate presentation were a ratemeter, howler, multichannel scaler, and HRM III. The HRM III calculates the statistical significance of the difference between current and previous count rates and presents the result as an audio signal. We tested six observers with each mode of count-rate presentation, calculated receiver operating characteristic (ROC) curves, and used the areas under the ROC curves to compare the different modes. Observer performance was better with the multichannel scaler and HRM III than with either the ratemeter or the howler. The results suggest that observer performance with devices that use ratemeters or howlers can be enhanced by improving the mode of count-rate presentation.

Splenic salvage quantified by uptake of heat-damaged radiolabeled red blood cells. Experimental and clinical studies.

We evaluated a noninvasive radionuclide technique to quantify splenic trapping function, which is a key step in the disposition of blood-borne particulates such as poorly opsonized encapsulated microorganisms implicated in hyposplenic fulminant sepsis. Using computerized external gamma imaging, the percentage of splenic uptake of heat-damaged radiolabeled red blood cells was determined in adult Sprague-Dawley rats with eutopic (partial splenectomy) or ectopic (single or multiple autotransplantation) remnants or whole spleens, and in 14 patients with either an intact spleen or splenic remnants after treatment for trauma or hypersplenism. The masses of both eutopic and ectopic remnants correlated directly with the percentage of heat-damaged red blood cell uptake, but the percentage of uptake per gram was higher in eutopic remnants, paralleling more vigorous compensatory growth. In patients, the percentage of heat-damaged red blood cell uptake by remnant spleens was similar to that seen in the rats and, in addition, was supernormal in those with congestive splenomegaly. This noninvasive technique both provides a vivid biplanar image and quantifies blood-borne particle trapping, which is a key splenic function. A heat-damaged red blood cell uptake of less than 15 percent after splenic salvage suggests marginal splenic performance and continued vulnerability to overwhelming sepsis.

Biliary imaging suggesting common duct obstruction in acute viral hepatitis. Case report.

A patient with right upper quadrant pain showed normal tracer extraction and a prolonged hepatocellular phase during biliary imaging, findings that are most consistent with complete common duct obstruction. He had no other evidence of biliary tract obstruction and was diagnosed subsequently as having viral hepatitis. Hepatitis must be considered when biliary imaging suggests complete common bile duct obstruction.

Acquired immunodeficiency syndrome: Ga-67 citrate imaging.

All gallium-67 citrate scans obtained in patients with acquired immunodeficiency syndrome (AIDS) at the Clinical Center, National Institutes of Health (Bethesda, Md.) were retrospectively analyzed and correlated with the results of bronchoscopy, chest radiography, and endoscopy. There were 164 scans of 95 patients. Twenty scans were from patients with Pneumocystis carinii pneumonia; 19 were abnormal, for a sensitivity of 95%. Ga-67 uptake tended to be less in patients receiving therapy for P. carinii pneumonia. Chest radiographs were normal at least initially in three patients with abnormal scans and P. carinii pneumonia. Unusually prominent colonic activity was associated with infection in some patients. No lesions of Kaposi sarcoma showed tracer uptake. Gallium scanning is useful for detecting P. carinii pneumonia and other opportunistic infections in patients with AIDS, but it is not useful for localizing Kaposi sarcoma.

Delivery of antifibroblast agents as adjuncts to filtration surgery. Part I--Periocular clearance of cobalt-57 bleomycin in experimental drug delivery: pilot study in the rabbit.

Antitumor and antifibroblast agents show promise as adjuncts after glaucoma filtration surgery in reducing postoperative scarring and failure. We used nuclear imaging in rabbits to investigate periocular clearance of one such agent (57Co-bleomycin). Sub-Tenon injection was compared to other delivery techniques. Our results showed that a collagen sponge and a silastic disc implant with a microhole prolonged drug delivery when compared to sub-Tenon injection alone or injection with a viscosity enhancing agent (0.5% sodium hyaluronate). We theorize that if an antifibroblast agent can be delivered in small and sustained amounts after filtration surgery, this may prolong bleb longevity and avoid unnecessary drug toxicity.

Hepatobiliary scintigraphy for cholestasis in congenital hepatic fibrosis. Diagnosis and treatment.

A 9-year-old child with congenital hepatic fibrosis had dilated intrahepatic bile ducts and recurrent cholangitis. Choleretic agents were administered to prevent recurrent cholangitis. Response to treatment was monitored with serum bile acid concentrations and computer-assisted technetium Tc 99m iprofenin (Pipida) scintigraphy. Dehydrocholic acid with meals improved hepatobiliary excretion of the radioactive isotope and lowered serum bile acid levels but did not prevent cholangitic attacks when used alone. Sulfamethoxazole and trimethoprim used alone prevented infection, but a steady rise in serum bile acid concentrations suggested increasing cholestasis. During combined drug treatment, the patient remained free of cholangitis for at least two years. Optimal therapy of congenital hepatic fibrosis with cholestasis but without mechanical biliary obstruction may involve the combined use of a choleretic such as dehydrocholic acid plus a suppressive antibiotic.

Rapid in vivo localization of a lost brachytherapy seed.

We adapted a small sodium iodide scintillation detector for rapid, in vivo localization of a lost brachytherapy seed. Using the detector, we were able to locate and remove an Ir-192 seed that was not visible to the unaided eye.

Hypercalcemia in coccidioidomycosis.

Two patients with disseminated coccidioidomycosis and hypercalcemia are presented. One patient studied showed normal levels of 25-hydroxyvitamin D with depressed levels of 1 alpha,25-dihydroxyvitamin D. The serum calcitonin level was appropriate for the level of serum calcium, and the serum parathyroid hormone level was suppressed with elevation of the nephrogenous cAMP level. Intestinal absorption of calcium was elevated at 63 percent. Hypercalcemia and hypercalciuria persisted despite a 300 mg calcium diet. An osteotropic substance similar to the humoral hypercalcemia of malignancy is postulated.