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.

Imaging doxorubicin and polymer-drug conjugates of doxorubicin-induced cardiotoxicity with bispecific anti-myosin-anti-DTPA antibody and Tc-99m-labeled polymers.

BACKGROUND: Radiolabeled anti-myosin imaging is well-established for imaging doxorubicin-induced cardiotoxicity. However, to enable imaging of drug-induced cardiotoxicity in small experimental animals, pretargeting with bispecific anti-myosin-anti-DTPA-Fab-Fab' and targeting with high-specific radioactivity Tc-99m-DTPA-succinylated-polylysine (DSPL) was developed. METHODS: Mice were injected biweekly with 10 mg/kg Dox or its equivalent as D-Dox-PGA. Tc-99m-DSPL myocardial activity after pretargeting with bsAb-Fab-Fab' was determined after gamma imaging performed at day 7 for Dox-treated mice and day 39 for all others. RESULTS: Mice treated with 10 mg/kg Dox lost 10% total body weight in 1 week and 20% after a second dose. Pretargeted mice treated with 30 mg/kg cumulative D-Dox-PGA dose showed no loss of body weight for the duration of the study. Cardiotoxicity was confirmed by gamma imaging and scintillation counting (1.9 ± 0.25 [mean% ID/g ± SD]) after 1 dose of Dox. Mice injected with 3 × 10 mg/kg Dox equivalent as D-Dox-PGA (0.4 ± 0.04, P < .01) and untreated 2 control groups (0.20 ± 0.05 and 0.19 ± 0.04, P < .01) showed significantly lower myocardial anti-myosin radioactivity relative to the 10 mg/kg Dox group. CONCLUSION: Pretargeting with bsAb-Fab-Fab' and targeting with Tc-99m labeled high-specific activity polymers enabled early visualization of doxorubicin induce cardiotoxicity in mice. Tolerated dose of D-Dox-PGA was greater than to 30 mg/kg Dox-equivalent dose with minimal cardiotoxicity.

Development and Design of Next-Generation Head-Mounted Ambulatory Microdose Positron-Emission Tomography (AM-PET) System.

Several applications exist for a whole brain positron-emission tomography (PET) brain imager designed as a portable unit that can be worn on a patient's head. Enabled by improvements in detector technology, a lightweight, high performance device would allow PET brain imaging in different environments and during behavioral tasks. Such a wearable system that allows the subjects to move their heads and walk-the Ambulatory Microdose PET (AM-PET)-is currently under development. This imager will be helpful for testing subjects performing selected activities such as gestures, virtual reality activities and walking. The need for this type of lightweight mobile device has led to the construction of a proof of concept portable head-worn unit that uses twelve silicon photomultiplier (SiPM) PET module sensors built into a small ring which fits around the head. This paper is focused on the engineering design of mechanical support aspects of the AM-PET project, both of the current device as well as of the coming next-generation devices. The goal of this work is to optimize design of the scanner and its mechanics to improve comfort for the subject by reducing the effect of weight, and to enable diversification of its applications amongst different research activities.

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.

Real-time motion-enabling positron emission tomography of the brain of upright ambulatory humans.

BACKGROUND: Mobile upright PET devices have the potential to enable previously impossible neuroimaging studies. Currently available options are imagers with deep brain coverage that severely limit head/body movements or imagers with upright/motion enabling properties that are limited to only covering the brain surface. METHODS: In this study, we test the feasibility of an upright, motion-compatible brain imager, our Ambulatory Motion-enabling Positron Emission Tomography (AMPET) helmet prototype, for use as a neuroscience tool by replicating a variant of a published PET/fMRI study of the neurocorrelates of human walking. We validate our AMPET prototype by conducting a walking movement paradigm to determine motion tolerance and assess for appropriate task related activity in motor-related brain regions. Human participants (n = 11 patients) performed a walking-in-place task with simultaneous AMPET imaging, receiving a bolus delivery of F18-Fluorodeoxyglucose. RESULTS: Here we validate three pre-determined measure criteria, including brain alignment motion artifact of less than <2 mm and functional neuroimaging outcomes consistent with existing walking movement literature. CONCLUSIONS: The study extends the potential and utility for use of mobile, upright, and motion-tolerant neuroimaging devices in real-world, ecologically-valid paradigms. Our approach accounts for the real-world logistics of an actual human participant study and can be used to inform experimental physicists, engineers and imaging instrumentation developers undertaking similar future studies. The technical advances described herein help set new priorities for facilitating future neuroimaging devices and research of the human brain in health and disease.

Brain imaging plays an important role in understanding how the human brain functions in both health and disease. However, traditional brain scanners often require people to remain still, limiting the study of the brain in motion, and excluding people who cannot remain still. To overcome this, our team developed an imager that moves with a person's head, which uses a suspended ring of lightweight detectors that fit to the head. Using our imager, we were able to obtain clear brain images of people walking in place that showed the expected brain activity patterns during walking. Further development of our imager could enable it to be used to better understand real-world brain function and behavior, enabling enhanced knowledge and treatment of neurological conditions.

Construction and Evaluation of a Prototype High Resolution, Silicon Photomultiplier-Based, Tandem Positron Emission Tomography System.

While the performance of most current commercially available PET scanners is sufficient for many standard clinical applications, some specific tasks likely require specialized imaging systems. The goal of this project is to explore the capabilities and limitations of a small, high-resolution prototype system for obtaining PET images. The scanner consists of a tandem of detectors. One is a small detector consisting of a 20 × 20 array of 0.7 × 0.7 × 3 mm3 (pitch 0.8 mm) LYSO elements. The scintillator array is coupled to an array of silicon photomultipliers. The second detector is a 96 × 72 array of 2 × 2 × 15 mm3 (pitch = 2.1 mm) LYSO elements coupled to PSPMTs. Separation between the two devices is 180 mm. The detectors are operated in coincidence with each other. Image reconstruction is performed using a limited angle, Maximum Likelihood Expectation Maximization (MLEM) algorithm. Evaluation of the device included measurements of spatial resolution and detection sensitivity as a function of distance. The transaxial radial and tangential spatial resolution of the system ranged from 0.6 mm to 0.9 mm FWHM; axial resolution ranged from 2.7 mm to 4.6 mm FWHM. Detection sensitivity ranged from 0.05 to 0.28%. Spatial resolution and field-of-view vary as a function of distance from the small detector. The tandem detector insert permitted differentiation of the smallest (1 mm diameter) rods in a mini-hot rod phantom. The results indicate that a tandem PET imaging scheme can be potentially employed in applications where high-resolution images over a small region are required.

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.

Intraoperative imaging guidance for sentinel node biopsy in melanoma using a mobile gamma camera.

OBJECTIVE: To evaluate the sensitivity and clinical utility of intraoperative mobile gamma camera (MGC) imaging in sentinel lymph node biopsy (SLNB) in melanoma. BACKGROUND: The false-negative rate for SLNB for melanoma is approximately 17%, for which failure to identify the sentinel lymph node (SLN) is a major cause. Intraoperative imaging may aid in detection of SLN near the primary site, in ambiguous locations, and after excision of each SLN. The present pilot study reports outcomes with a prototype MGC designed for rapid intraoperative image acquisition. We hypothesized that intraoperative use of the MGC would be feasible and that sensitivity would be at least 90%. METHODS: From April to September 2008, 20 patients underwent Tc99 sulfur colloid lymphoscintigraphy, and SLNB was performed with use of a conventional fixed gamma camera (FGC), and gamma probe followed by intraoperative MGC imaging. Sensitivity was calculated for each detection method. Intraoperative logistical challenges were scored. Cases in which MGC provided clinical benefit were recorded. RESULTS: Sensitivity for detecting SLN basins was 97% for the FGC and 90% for the MGC. A total of 46 SLN were identified: 32 (70%) were identified as distinct hot spots by preoperative FGC imaging, 31 (67%) by preoperative MGC imaging, and 43 (93%) by MGC imaging pre- or intraoperatively. The gamma probe identified 44 (96%) independent of MGC imaging. The MGC provided defined clinical benefit as an addition to standard practice in 5 (25%) of 20 patients. Mean score for MGC logistic feasibility was 2 on a scale of 1-9 (1 = best). CONCLUSIONS: Intraoperative MGC imaging provides additional information when standard techniques fail or are ambiguous. Sensitivity is 90% and can be increased. This pilot study has identified ways to improve the usefulness of an MGC for intraoperative imaging, which holds promise for reducing false negatives of SLNB for melanoma.

Quantification of radiotracer uptake with a dedicated breast PET imaging system.

Tomographic breast imaging techniques can be used to quantify radiotracer uptake in breast and tumor tissue. However, physical processes common to PET imaging can confound accurate quantification. In this investigation, we assessed the effects of these phenomena and tested correction schemes for our new positron emission mammography-tomography system (PEM-PET). The PEM-PET scanner utilizes two sets of rotating planar detector heads. Each unit consists of a 4 x 3 array of Hamamatsu H8500 flat panel position sensitive photomultipliers coupled to a 96 x 72 array of 2 x 2 x 15 mm3 LYSO detector elements (pitch = 2.1 mm). Image reconstruction is performed with a 3D-OSEM algorithm parallelized to run on a multiprocessor computer system. The reconstructed field-of-view is 15 x 15 x 15 cm3. Much of the testing procedures were based on NEMA-NU2/2001 protocols. Count rate losses due to pulse pile-up, image contamination due to acceptance of random coincidences and Compton scatter, and image artifacts produced by photon attenuation were measured. It was found that the system was susceptible to count rate losses when moderate levels of radiation were present in the scanner due to the current design of the event trigger electronics. Application of corrections for Compton scattering, photon attenuation and dead time resulted in improved estimations of 18F concentration in simplified phantom studies. Results from these preliminary studies indicate that the PEM-PET scanner will be useful for the quantification of radiotracer uptake in breast tumors, possibly facilitating early assessment of cancer treatments.

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.

Feasibility Study of a Small Animal PET Insert Based on a Single LYSO Monolithic Tube.

There are drawbacks with using a Positron Emission Tomography (PET) scanner design employing the traditional arrangement of multiple detectors in an array format. Typically PET systems are constructed with many regular gaps between the detector modules in a ring or box configuration, with additional axial gaps between the rings. Although this has been significantly reduced with the use of the compact high granularity SiPM photodetector technology, such a scanner design leads to a decrease in the number of annihilation photons that are detected causing lower scanner sensitivity. Moreover, the ability to precisely determine the line of response (LOR) along which the positron annihilated is diminished closer to the detector edges because the spatial resolution there is degraded due to edge effects. This happens for both monolithic based designs, caused by the truncation of the scintillation light distribution, but also for detector blocks that use crystal arrays with a number of elements that are larger than the number of photosensors and, therefore, make use of the light sharing principle. In this report we present a design for a small-animal PET scanner based on a single monolithic annulus-like scintillator that can be used as a PET insert in high-field Magnetic Resonance systems. We provide real data showing the performance improvement when edge-less modules are used. We also describe the specific proposed design for a rodent scanner that employs facetted outside faces in a single LYSO tube. In a further step, in order to support and prove the proposed edgeless geometry, simulations of that scanner have been performed and lately reconstructed showing the advantages of the design.

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.

Light sharing in multi-flat-panel-PMT PEM detectors.

Large are a detectors, such as those used in positron emission mammography (PEM) and scintimammography, utilize arrays of discrete semtillator elements mounted on arrays of position sensitive photomultiplier tubes (PSPMT). Scintillator elements can be packed very densely (minimizing area between elements), allowing good detection sensitivity and spatial resolution. And, while new flat panel PSPMTS have minimal inactive edges, when they are placed in arrays significant dead spaces where scintillation light is undetectable are created. To address this problem, a light guide is often placed between the detector and PSPMT array to spread scintillation light so that these gaps can be bridged. In this investigation we studied the effect of light guides of various thickness on system performance. A 10x10 element array of LYSO detector elements was coupled to the center of a 2x2 array of PSPMTs through varying thicknesses (1 to 4 mm) of UV glass. The spot size of the imaged elements and distortions in the regular square pattern of the imaged scintillator arrays were evaluated. Energy resolution was measured by placing single elements of LYSO at several locations of the PSPMT array. Spatial distortions in the images of the array were reduced by using thicker light guides (3-4 mm). Use of thicker light guides, however, resulted in reduced pixel resolution and slight degradation of energy resolution. Therefore, some loss of pixel and energy resolution will accompany the use of thick light guides (minimum of 3 mm) required for optimum identification of detector elements.

Quality assurance procedure for a gamma guided stereotactic breast biopsy system.

A quality assurance procedure has been developed for a prototype gamma-ray guided stereotactic biopsy system. The system consists of a compact small-field-of-view gamma-ray camera mounted to the rotational arm of a Lorad stereotactic biopsy system. The small-field-of-view gamma-ray camera has been developed for clinical applications where mammographic X-ray localization is not possible. Marker sources that can be imaged with the gamma-camera have been designed and built for quality assurance testing and to provide a fiducial reference mark. An algorithm for determining the three dimensional location of a region of interest, such as a lesion, relative to the fiducial mark has been implemented into the software control of the camera. This system can be used to determine the three-dimensional location of a region of interest from a stereo pair of images and that information can be used to guide a biopsy needle to that site. Point source phantom tests performed with the system have demonstrated that the camera can be used to localize a point of interest to within 1 mm, which is satisfactory for its use in needle localization.

Lesion radioactivity concentration estimation using dual modality gamma ray/X-ray imaging.

Although the use of dedicated gamma cameras in scintimammography permits closer access to the breast and improved spatial resolution relative to conventional gamma cameras, the task of quantifying the radiotracer concentration in the lesion relative to that in the surrounding breast tissue remains challenging because of the lesion-depth-dependent effects of attenuation and collimator blur. We are developing a dual modality scanner that combines digital x-ray mammography and a dedicated gamma camera on a common upright gantry. Here we present the results of a phantom study evaluating the use of the dual modality system for quantifying radioactivity in breast lesions. In addition to assessment of lesion activity, lesion volume estimates are necessary to quantify lesion radioactivity concentration. We have used multiple view x-ray imaging as a means of estimating lesion volume. Using phantom experiments, we have empirically derived a formula for correction of the measured z dimension of the lesion. The error obtained in quantification of lesion activity is approximately 10%. Lesion volume can be assessed with an accuracy comparable to that of lesion activity assessment using five x-ray views. These results suggest that the error in lesion concentration assessment is approximately 14%.

Phantom evaluations of a dedicated dual-head scintimammography system.

Results of aboratory evaluations are presented of the dual-head scintimammography system using two opposed and co-registered compact gamma heads. The system is intended for clinical studies imaging suspicious lesions in a compressed breast. The studies were performed using 5 cm and 6 cm compressed breast phantoms with lesion sizes from 6 to 10 mm and lesion to breast tissue activity ratios from 6 to 10. Two imagers with a field-of-view (FOV) of 15 cmx20 cm were placed on the opposite sides of the breast phartoms. In some studies anthropomorphic torso phantom was used to simulate realistic scatter gamma radiation field. Two types of parallel-hole lead collimators were employed. Combining the co-registered images from both detector heads resulted in an over two-fold increase in lesioin contrast in the central plane of the phantom and substantially increased detection sensitivity over the whole breast volume, especially of asymmetrically placed small lesions. The results confirm the important advantage of a co-registoed two-head scintimammography system over a single head system in lesion detection and localization.