Evaluation of Preoperative and Intraoperative Mobile Gamma Camera Imaging in Sentinel Lymph Node Biopsy for Melanoma Independent of Preoperative Lymphoscintigraphy.

INTRODUCTION: Sentinel lymph node biopsy (SLNB) is a standard practice for staging cutaneous melanoma. High false-negative rates have an increased interest in adjunctive techniques for localizing SLNs. Mobile gamma cameras (MGCs) represent potential tools to enhance SLNB performance. METHODS: An institutional review board approval was obtained for this study (ClinicalTrials.gov ID NCT01531608). After obtaining informed consent, 20 eligible melanoma patients underwent 99mTc sulfur colloid injection and standard lymphoscintigraphy with a fixed gamma camera (FGC). A survey using a 20 cm square MGC, performed immediately preoperatively by the study surgeon, was used to establish an operative plan while blinded to the FGC results. Subsequently, SLNB was performed using a gamma probe and a novel 6 cm diameter handheld MGC. RESULTS: A total of 24 SLN basins were detected by FGC. Prior to unblinding, all 24 basins were identified with the preoperative MGC and the operative plan established by preoperative MGC imaging was confirmed accurate by review of the FGC images. All individual sentinel lymph nodes were identified during intraoperative MGC imaging, and in 5/24 (21%) cases, surgeon-reported additional clinically useful information was obtained from the MGC. CONCLUSIONS: Preoperative MGC images provide information consistent with FGC images for planning SLNB and in some cases provide additional information that aided in surgical decision-making.

The United States Department of Energy and National Institutes of Health Collaboration: Medical Care Advances via Discovery in Physical Sciences.

Over several months, representatives from the U.S. Department of Energy (DOE) Office of Science and National Institutes of Health (NIH) had a number of meetings that lead to the conclusion that innovations in the Nation's health care could be realized by more directed interactions between NIH and DOE. It became clear that the expertise amassed and instrumentation advances developed at the DOE physical science laboratories to enable cutting-edge research in particle physics could also feed innovation in medical healthcare. To meet their scientific mission, the DOE laboratories created advances in such technologies as particle beam generation, radioisotope production, high-energy particle detection and imaging, superconducting particle accelerators, superconducting magnets, cryogenics, high-speed electronics, artificial intelligence, and big data. To move forward, NIH and DOE initiated the process of convening a joint workshop which occurred on July 12th and 13th, 2021. This Special Report presents a summary of the findings of the collaborative workshop and introduces the goals of the next one.

Evaluation of camera-based freehand SPECT in preoperative sentinel lymph node mapping for melanoma patients.

BACKGROUND: Assessment of lymphatic status via sentinel lymph node (SLN) biopsy is an integral and crucial part of melanoma surgical oncology. The most common technique for sentinel node mapping is preoperative planar scintigraphy of an injected gamma-emitting lymphatic tracer followed by intraoperative node localization using a non-imaging gamma probe with auditory feedback. In recent years, intraoperative visualization of SLNs in 3D has become possible by coupling the probe to an external system capable of tracking its location and orientation as it is read out, thereby enabling computation of the 3D distribution of the tracer (freehand SPECT). In this project, the non-imaging probe of the fhSPECT system was replaced by a unique handheld gamma camera containing an array of sodium iodide crystals optically coupled to an array of silicon photomultipliers (SiPMs). A feasibility study was performed in which preoperative SLN mapping was performed using camera fhSPECT and the number of detected nodes was compared to that visualized by lymphoscintigraphy, probe fhSPECT, and to the number ultimately excised under non-imaging probe guidance. RESULTS: Among five subjects, SLNs were detected in nine lymphatic basins, with one to five SLNs detected per basin. A basin-by-basin comparison showed that the number of SLNs detected using camera fhSPECT exceeded that using lymphoscintigraphy and probe fhSPECT in seven of nine basins and five of five basins, respectively. (Probe fhSPECT scans were not performed for four basins.) It exceeded the number excised under non-imaging probe guidance for seven of nine basins and equaled the number excised for the other two basins. CONCLUSIONS: Freehand SPECT using a prototype SiPM-based gamma camera demonstrates high sensitivity for detection of SLNs in a preoperative setting. Camera fhSPECT is a potential means for efficiently obtaining real-time 3D activity distribution maps in applications such as image-guided percutaneous biopsy, and surgical SLN biopsy or radioguided tumor excision.

Evaluation of a novel collimator for molecular breast tomosynthesis.

PURPOSE: This study investigated a novel gamma camera for molecular breast tomosynthesis (MBT), which is a nuclear breast imaging method that uses limited angle tomography. The camera is equipped with a variable angle, slant-hole (VASH) collimator that allows the camera to remain close to the breast throughout the acquisition. The goal of this study was to evaluate the spatial resolution and count sensitivity of this camera and to compare contrast and contrast-to-noise ratio (CNR) with conventional planar imaging using an experimental breast phantom. METHODS: The VASH collimator mounts to a commercial gamma camera for breast imaging that uses a pixelated (3.2 mm), 15 × 20 cm NaI crystal. Spatial resolution was measured in planar images over a range of distances from the collimator (30-100 mm) and a range of slant angles (-25° to 25°) using 99m Tc line sources. Spatial resolution was also measured in reconstructed MBT images including in the depth dimension. The images were reconstructed from data acquired over the -25° to 25° angular range using an iterative algorithm adapted to the slant-hole geometry. Sensitivity was measured over the range of slant angles using a disk source. Measured spatial resolution and sensitivity were compared to theoretical values. Contrast and CNR were measured using a breast phantom containing spherical lesions (6.2 mm and 7.8 mm diameter) and positioned over a range of depths in the phantom. The MBT and planar methods had equal scan time, and the count density in the breast phantom data was similar to that in clinical nuclear breast imaging. The MBT method used an iterative reconstruction algorithm combined with a postreconstruction Metz filter. RESULTS: The measured spatial resolution in planar images agreed well with theoretical calculations over the range of distances and slant angles. The measured FWHM was 9.7 mm at 50 mm distance. In reconstructed MBT images, the spatial resolution in the depth dimension was approximately 2.2 mm greater than the other two dimensions due to the limited angle data. The measured count sensitivity agreed closely with theory over all slant angles when using a wide energy window. At 0° slant angle, measured sensitivity was 19.7 counts sec-1 µCi-1 with the open energy window and 11.2 counts sec-1 µCi-1 with a 20% wide photopeak window (126 to 154 keV). The measured CNR in the MBT images was significantly greater than in the planar images for all but the lowest CNR cases where the lesion detectability was extremely low for both MBT and planar. The 7.8 mm lesion at 37 mm depth was marginally detectable in the planar image but easily visible in the MBT image. The improved CNR with MBT was due to a large improvement in contrast, which out-weighed the increase in image noise. CONCLUSION: The spatial resolution and count sensitivity measurements with the prototype MBT system matched theoretical calculations, and the measured CNR in breast phantom images was generally greater with the MBT system compared to conventional planar imaging. These results demonstrate the potential of the proposed MBT system to improve lesion detection in nuclear breast imaging.

Bispecific antibody complex pre-targeting and targeted delivery of polymer drug conjugates for imaging and therapy in dual human mammary cancer xenografts: targeted polymer drug conjugates for cancer diagnosis and therapy.

INTRODUCTION: Doxorubicin, a frontline chemotherapeutic agent, limited by its cardiotoxicity and other tissue toxicities, was conjugated to N-terminal DTPA-modified polyglutamic acid (D-Dox-PGA) to produce polymer pro-drug conjugates. D-Dox-PGA or Tc-99 m labeled DTPA-succinyl-polylysine polymers (DSPL) were targeted to HER2-positive human mammary carcinoma (BT-474) in a double xenografted SCID mouse model also hosting HER2-negative human mammary carcinoma (BT-20). METHODS: After pretargeting with bispecific anti-HER2-affibody-anti-DTPA-Fab complexes (BAAC), anti-DTPA-Fab or only phosphate buffered saline, D-Dox-PGA or Tc-99 m DSPL were administered. Positive therapeutic control mice were injected with Dox alone at maximum tolerated dose (MTD). RESULTS: Only BT-474 lesions were visualized by gamma imaging with Tc-99 m-DSPL; BT-20 lesions were not. Therapeutic efficacy was equivalent in mice pretargeted with BAAC/targeted with D-Dox-PGA to mice treated only with doxorubicin. There was no total body weight (TBW) loss at three times the doxorubicin equivalent MTD with D-Dox-PGA, whereas mice treated with doxorubicin lost 10% of TBW at 2 weeks and 16% after the second MTD injection leading to death of all mice. CONCLUSIONS: Our cancer imaging and pretargeted therapeutic approaches are highly target specific, delivering very high specific activity reagents that may result in the development of a novel theranostic application. HER/2 neu specific affibody-anti-DTPA-Fab bispecific antibody pretargeting of HER2 positive human mammary xenografts enabled exquisite targeting of polymers loaded with radioisotopes for molecular imaging and doxorubicin for effective therapy without the associating non-tumor normal tissue toxicities.

Development and characterization of a round hand-held silicon photomultiplier based gamma camera for intraoperative imaging.

This paper describes the development of a hand-held gamma camera for intraoperative surgical guidance that is based on silicon photomultiplier (SiPM) technology. The camera incorporates a cerium doped lanthanum bromide (LaBr3:Ce) plate scintillator, an array of 80 SiPM photodetectors and a two-layer parallel-hole collimator. The field of view is circular with a 60 mm diameter. The disk-shaped camera housing is 75 mm in diameter, approximately 40.5 mm thick and has a mass of only 1.4 kg, permitting either hand-held or arm-mounted use. All camera components are integrated on a mobile cart that allows easy transport. The camera was developed for use in surgical procedures including determination of the location and extent of primary carcinomas, detection of secondary lesions and sentinel lymph node biopsy (SLNB). Here we describe the camera design and its principal operating characteristics, including spatial resolution, energy resolution, sensitivity uniformity, and geometric linearity. The gamma camera has an intrinsic spatial resolution of 4.2 mm FWHM, an energy resolution of 21.1 % FWHM at 140 keV, and a sensitivity of 481 and 73 cps/MBq when using the single- and double-layer collimators, respectively.

Molecular imaging of conscious, unrestrained mice with AwakeSPECT.

UNLABELLED: We have developed a SPECT imaging system, AwakeSPECT, to enable molecular brain imaging of untrained mice that are conscious, unanesthetized, and unrestrained. We accomplished this with head tracking and motion correction techniques. METHODS: The capability of the system for motion-corrected imaging was demonstrated with a (99m)Tc-pertechnetate phantom, (99m)Tc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand (123)I-ioflupane in mouse brain in the awake and anesthetized (isoflurane) states. Stress induced by imaging in the awake state was assessed through measurement of plasma corticosterone levels. RESULTS: AwakeSPECT provided high-resolution bone images reminiscent of those obtained from CT. The binding potential of (123)I-ioflupane in the awake state was on the order of 50% of that obtained with the animal under anesthesia, consistent with previous studies in nonhuman primates. Levels of stress induced were on the order of those seen in other behavioral tasks and imaging studies of awake animals. CONCLUSION: These results demonstrate the feasibility of SPECT molecular brain imaging of mice in the conscious, unrestrained state and demonstrate the effects of isoflurane anesthesia on radiotracer uptake.

PhytoBeta imager: a positron imager for plant biology.

Several positron emitting radioisotopes such as (11)C and (13)N can be used in plant biology research. The (11)CO(2) tracer is used to facilitate plant biology research toward optimization of plant productivity, biofuel development and carbon sequestration in biomass. Positron emission tomography (PET) imaging has been used to study carbon transport in live plants using (11)CO(2). Because plants typically have very thin leaves, little medium is present for the emitted positrons to undergo an annihilation event. The emitted positrons from (11)C (maximum energy 960 keV) could require up to approximately 4 mm of water equivalent material for positron annihilation. Thus many of the positrons do not annihilate inside the leaf, resulting in limited sensitivity for PET imaging. To address this problem we have developed a compact beta-positive, beta-minus particle imager (PhytoBeta imager) for (11)CO(2) leaf imaging. The detector is based on a Hamamatsu H8500 position sensitive photomultiplier tube optically coupled via optical grease to a 0.5 mm thick Eljen EJ-212 plastic scintillator. The detector is equipped with a flexible arm to allow its placement and orientation over or under the leaf to be studied while maintaining the leaf's original orientation. To test the utility of the system the detector was used to measure carbon translocation in a leaf of the spicebush (Lindera benzoin) under two transient light conditions.

Imaging small human prostate cancer xenografts after pretargeting with bispecific bombesin-antibody complexes and targeting with high specific radioactivity labeled polymer-drug conjugates.

PURPOSE: Pretargeting with bispecific monoclonal antibodies (bsMAb) for tumor imaging was developed to enhance target to background activity ratios. Visualization of tumors was achieved by the delivery of mono- and divalent radiolabeled haptens. To improve the ability to image tumors with bsMAb, we have combined the pretargeting approach with targeting of high specific activity radiotracer labeled negatively charged polymers. The tumor antigen-specific antibody was replaced with bombesin (Bom), a ligand that binds specifically to the growth receptors that are overexpressed by many tumors including prostate cancer. Bomanti- diethylenetriaminepentaacetic acid (DTPA) bispecific antibody complexes were used to demonstrate pretargeting and imaging of very small human prostate cancer xenografts targeted with high specific activity ¹¹¹In- or 99mTc-labeled negatively charged polymers. METHODS: Bispecific antibody complexes consisting of intact anti-DTPA antibody or Fab' linked to Bom via thioether bonds (Bom-bsCx or Bom-bsFCx, respectively) were used to pretarget PC-3 human prostate cancer xenografts in SCID mice. Negative control mice were pretargeted with Bom or anti-DTPA Ab. 111In-Labeled DTPA-succinyl polylysine (DSPL) was injected intravenously at 24 h (7.03 ± 1.74 or 6.88 ± 1.89 MBq ¹¹¹In-DSPL) after Bom-bsCx or 50 ± 5.34 MBq of 99mTc-DSPL after Bom-bsFCx pretargeting, respectively. Planar or single photon emission computed tomography (SPECT)/CT gamma images were obtained for up to 3 h and only planar images at 24 h. After imaging, all mice were killed and biodistribution of 111In or 99mTc activities were determined by scintillation counting. RESULTS: Both planar and SPECT/CT imaging enabled detection of PC-3 prostate cancer lesions less than 1-2 mm in diameter in 1-3 h post 111In-DSPL injection. No lesions were visualized in Bom or anti-DTPA Ab pretargeted controls. 111In-DSPL activity in Bom-bsCx pretargeted tumors (1.21 ± 0.36 %ID/g) was 5.4 times that in tumors pretargeted with Bom or anti-DTPA alone (0.22 ± 0.08, p = 0.001). PC-3 xenografts pretargeted with Bom-bsFCx and targeted with 99mTc-DSPL were visualizable by 1-3 h. Exquisite tumor uptake at 24 h (6.54 ± 1.58 %ID/g) was about 15 times greater than that of Bom pretargeted controls (0.44 ± 0.17, p = 0.002). CONCLUSION: Pretargeting prostate cancer with Bom-bsCx or Bom-bsFCx enabled fast delivery of high specific radioactivity ¹¹¹In- or 99mTc-labeled polymer-drug conjugates resulting in visualization of lesions smaller than 1- 2 mm in diameter within 3 h.

Motion-tracking technique in unrestrained small-animal single-photon emission computed tomography.

Medical researchers have used structural and functional imaging techniques to study various neurological phenomena. Humans are typically conscious for both structural and functional neuroimaging studies. The use of functional neuro-imaging techniques in mouse-based animal models is typically accomplished with restrained or anesthetized mice. A system was developed to perform functional imaging with single-photon emission computed tomography of awake mice to avoid the confounding influences of anesthesia or physical restraint. This review article provides an overview of the technique and how it is presently being used. The system is designed for brain imaging and uses infrared reflectors to track the head position as a function of time. The detected photons are acquired in list mode and are time-stamped. The position of the rotating gamma camera is also recorded as a function of time. These three sets of data are integrated together in an iterative image reconstruction program that performs motion compensation. The successful performance of the system is demonstrated in moving phantom and awake animal studies. The system and methodology has the potential of being a powerful tool in behavioral neuroimaging studies involving awake, unrestrained mice.

MONICA: a compact, portable dual gamma camera system for mouse whole-body imaging.

INTRODUCTION: We describe a compact, portable dual-gamma camera system (named "MONICA" for MObile Nuclear Imaging CAmeras) for visualizing and analyzing the whole-body biodistribution of putative diagnostic and therapeutic single photon emitting radiotracers in animals the size of mice. METHODS: Two identical, miniature pixelated NaI(Tl) gamma cameras were fabricated and installed "looking up" through the tabletop of a compact portable cart. Mice are placed directly on the tabletop for imaging. Camera imaging performance was evaluated with phantoms and field performance was evaluated in a weeklong In-111 imaging study performed in a mouse tumor xenograft model. RESULTS: Tc-99m performance measurements, using a photopeak energy window of 140 keV+/-10%, yielded the following results: spatial resolution (FWHM at 1 cm), 2.2 mm; sensitivity, 149 cps (counts per seconds)/MBq (5.5 cps/microCi); energy resolution (FWHM, full width at half maximum), 10.8%; count rate linearity (count rate vs. activity), r(2)=0.99 for 0-185 MBq (0-5 mCi) in the field of view (FOV); spatial uniformity, <3% count rate variation across the FOV. Tumor and whole-body distributions of the In-111 agent were well visualized in all animals in 5-min images acquired throughout the 168-h study period. CONCLUSION: Performance measurements indicate that MONICA is well suited to whole-body single photon mouse imaging. The field study suggests that inter-device communications and user-oriented interfaces included in the MONICA design facilitate use of the system in practice. We believe that MONICA may be particularly useful early in the (cancer) drug development cycle where basic whole-body biodistribution data can direct future development of the agent under study and where logistical factors, e.g., limited imaging space, portability and, potentially, cost are important.

The positron emission mammography/tomography breast imaging and biopsy system (PEM/PET): design, construction and phantom-based measurements.

Tomographic breast imaging techniques can potentially improve detection and diagnosis of cancer in women with radiodense and/or fibrocystic breasts. We have developed a high-resolution positron emission mammography/tomography imaging and biopsy device (called PEM/PET) to detect and guide the biopsy of suspicious breast lesions. PET images are acquired to detect suspicious focal uptake of the radiotracer and guide biopsy of the area. Limited-angle PEM images could then be used to verify the biopsy needle position prior to tissue sampling. The PEM/PET scanner consists of two sets of rotating planar detector heads. Each detector consists of a 4 x 3 array of Hamamatsu H8500 flat panel position sensitive photomultipliers (PSPMTs) coupled to a 96 x 72 array of 2 x 2 x 15 mm(3) LYSO detector elements (pitch = 2.1 mm). Image reconstruction is performed with a three-dimensional, ordered set expectation maximization (OSEM) algorithm parallelized to run on a multi-processor computer system. The reconstructed field of view (FOV) is 15 x 15 x 15 cm(3). Initial phantom-based testing of the device is focusing upon its PET imaging capabilities. Specifically, spatial resolution and detection sensitivity were assessed. The results from these measurements yielded a spatial resolution at the center of the FOV of 2.01 +/- 0.09 mm (radial), 2.04 +/- 0.08 mm (tangential) and 1.84 +/- 0.07 mm (axial). At a radius of 7 cm from the center of the scanner, the results were 2.11 +/- 0.08 mm (radial), 2.16 +/- 0.07 mm (tangential) and 1.87 +/- 0.08 mm (axial). Maximum system detection sensitivity of the scanner is 488.9 kcps microCi(-1) ml(-1) (6.88%). These promising findings indicate that PEM/PET may be an effective system for the detection and diagnosis of breast cancer.

A small-animal imaging system capable of multipinhole circular/helical SPECT and parallel-hole SPECT.

We have designed and built a small animal single photon emission computed tomography (SPECT) imaging system equipped with parallel-hole and multipinhole collimators and capable of circular or helical SPECT. Copper-beryllium parallel-hole collimators suitable for imaging the ~35 keV photons from the decay of (125)I have been built and installed to achieve useful spatial resolution over a range of object-detector distances and to reduce imaging time on our dual-detector array. To address the resolution limitations in the parallel-hole SPECT and the sensitivity and limited field of view of single-pinhole SPECT, we have incorporated multipinhole circular and helical SPECT in addition to expanding the parallel-hole SPECT capabilities. The pinhole SPECT system is based on a 110 mm diameter circular detector equipped with a pixellated NaI(Tl) scintillator array (1x1x5 mm(3)/pixel). The helical trajectory is accomplished by two stepping motors controlling the rotation of the detector-support gantry and displacement of the animal bed along the axis of rotation of the gantry. Results obtained in SPECT studies of various phantoms show an enlarged field of view, very good resolution and improved sensitivity using multipinhole circular or helical SPECT. Collimators with one, three and five 1 mm diameter pinholes have been implemented and compared in these tests. Our objective is to develop a system on which one may readily select a suitable mode of either parallel-hole SPECT or pinhole circular or helical SPECT for a variety of small animal imaging applications.

Imaging of mesenchymal stem cell transplant by bioluminescence and PET.

UNLABELLED: Dynamic measurements of infused stem cells generally require animal euthanasia for single-time-point determinations of engraftment. In this study, we used a triple-fusion reporter system for multimodal imaging to monitor human mesenchymal stem cell (hMSC) transplants. METHODS: hMSCs were transduced with a triple-fusion reporter, fluc-mrfp-ttk (encoding firefly luciferase, monomeric red fluorescent protein, and truncated herpes simplex virus type 1 sr39 thymidine kinase) by use of a lentiviral vector. Transduced cells were assayed in vitro for the expression of each functional component of the triple-fusion reporter. Transduced and control hMSCs were compared for their potential to differentiate into bone, cartilage, and fat. hMSCs expressing the reporter were then loaded into porous, fibronectin-coated ceramic cubes and subcutaneously implanted into NOD-SCID mice along with cubes that were loaded with wild-type hMSCs and empty cubes. Mice were imaged repeatedly over 3 mo by bioluminescence imaging (BLI), and selected animals underwent CT and PET imaging. RESULTS: Osteogenic, adipogenic, and chondrogenic potential assays revealed retained differentiation potentials between transduced and wild-type hMSCs. Signals from the cubes loaded with reporter-transduced hMSCs were visible by BLI over 3 mo. There was no signal from the empty or wild-type hMSC-loaded control cubes. PET data provided confirmation of the quantitative estimation of the number of cells at one spot (cube). Cubes were removed from some animals, and histologic evaluations showed bone formation in cubes loaded with either reporter-transduced or wild-type hMSCs, whereas empty controls were negative for bone formation. CONCLUSION: The triple-fusion reporter approach resulted in a reliable method of labeling stem cells for investigation in small-animal models by use of both BLI and small-animal PET imaging. It has the potential for translation into future human studies with clinical PET.

Simultaneous acquisition of magnetic resonance spectroscopy (MRS) data and positron emission tomography (PET) images with a prototype MR-compatible, small animal PET imager.

Multi-modality imaging (such as PET-CT) is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET, fused with anatomical images created by MRI, allow the correlation of form with function. Perhaps more exciting than the combination of anatomical MRI with PET, is the melding of PET with MR spectroscopy (MRS). Thus, two aspects of physiology could be combined in novel ways to produce new insights into the physiology of normal and pathological processes. Our team is developing a system to acquire MRI images and MRS spectra, and PET images contemporaneously. The prototype MR-compatible PET system consists of two opposed detector heads (appropriate in size for small animal imaging), operating in coincidence mode with an active field-of-view of approximately 14 cm in diameter. Each detector consists of an array of LSO detector elements coupled through a 2-m long fiber optic light guide to a single position-sensitive photomultiplier tube. The use of light guides allows these magnetic field-sensitive elements of the PET imager to be positioned outside the strong magnetic field of our 3T MRI scanner. The PET scanner imager was integrated with a 12-cm diameter, 12-leg custom, birdcage coil. Simultaneous MRS spectra and PET images were successfully acquired from a multi-modality phantom consisting of a sphere filled with 17 brain relevant substances and a positron-emitting radionuclide. There were no significant changes in MRI or PET scanner performance when both were present in the MRI magnet bore. This successful initial test demonstrates the potential for using such a multi-modality to obtain complementary MRS and PET data.

A gamma camera re-evaluation of potassium iodide blocking efficiency in mice.

The protection of the thyroid against radioiodine uptake has been an important safety concern for decades. After several studies examined potassium iodide blockade efficacy in the 1960's and 1970's, a standard dosage was prescribed by both the World Health Organization and the U.S. Food and Drug Administration. In this paper, we tested the effectiveness of a scaled version of that standard dosage in comparison to higher doses in mice. A novel gamma camera was employed with a high spatial resolution for precisely quantifying activity within the thyroid and a field of view large enough to image the entire mouse body. Thyroid and whole-body 125I biodistribution was analyzed immediately after exposure and 1 and 7 days later. It was found that 1 h after exposure five times the scaled human dose blocked thyroid uptake about 40% more effectively than the 1X scaled dose. Even after 1 d and 7 d, five times the recommended scaled human dose blocked approximately 10% more effectively than the 1X dose. These data suggest the need for continued evaluation of the effectiveness of KI as a blocking agent and the application of novel, non-invasive technologies to this important human health issue.

Simultaneous MRI and PET imaging of a rat brain.

Multi-modality imaging is rapidly becoming a valuable tool in the diagnosis of disease and in the development of new drugs. Functional images produced with PET fused with anatomical structure images created by MRI will allow the correlation of form with function. Our group is developing a system to acquire MRI and PET images contemporaneously. The prototype device consists of two opposed detector heads, operating in coincidence mode. Each MRI-PET detector module consists of an array of LSO detector elements coupled through a long fibre optic light guide to a single Hamamatsu flat panel position-sensitive photomultiplier tube (PSPMT). The use of light guides allows the PSPMTs to be positioned outside the bore of a 3T MRI scanner where the magnetic field is relatively small. To test the device, simultaneous MRI and PET images of the brain of a male Sprague Dawley rat injected with FDG were successfully obtained. The images revealed no noticeable artefacts in either image set. Future work includes the construction of a full ring PET scanner, improved light guides and construction of a specialized MRI coil to permit higher quality MRI imaging.

Positron emission mammography with tomographic acquisition using dual planar detectors: initial evaluations.

Positron emission mammography (PEM) with tomographic acquisition using dual planar detectors rotating about the breast can obtain complete angular sampling and has the potential to improve activity estimation compared with PEM using stationary detectors. PEM tomography (PEMT) was compared with stationary PEM for point source and compressed breast phantom studies performed with a compact dual detector system. The acquisition geometries were appropriate for the target application of PEM guidance of stereotactic core biopsy. Images were reconstructed with a three-dimensional iterative maximum likelihood expectation maximization algorithm. PEMT eliminated blurring normal to the detectors seen with stationary PEM. Depth of interaction effects distorted the shape of the point spread functions for PEMT as the angular range from normal incidence of lines of response used in image reconstruction increased. Streak artefacts in PEMT for large detector rotation increments led to the development of an expression for the maximum rotation increment that maintains complete angular sampling. Studies with a compressed breast phantom were used to investigate contrast and signal-to-noise ratio (SNR) trade-offs for different sized spherical tumour models. PEMT and PEM both had advantages depending on lesion size and detector separation. The most appropriate acquisition method for specific detection or quantitation tasks requires additional investigation.

Combined structural and functional imaging of the breast.

Scintimammography, or single gamma nuclear imaging of the breast, has shown promise as a way of characterizing certain biological properties of suspicious breast masses. Conventional scintimammography, performed using large clinical gamma cameras and prone patient positioning suffers from several drawbacks including poor sensitivity for small (> 1 cm) lesions and no reliable method for correlating scintigraphic findings with those of other imaging modalities. We are developing a system designed to overcome some of these problems. The system combines x-ray mammography with scintimammography on a common gantry. The x-ray and gamma ray images are obtained in quick succession, with the breast in a common configuration under mild compression. A digital x-ray detector is used, permitting rapid assessment of lesion location prior to gamma imaging, and enabling fusion of the x-ray transmission and gamma emission information in a single digital image. In a pilot clinical diagnostic study, the system has demonstrated high pathology-proven accuracy in differentiating benign and malignant masses.