Stan Majewski

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.

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.

Imaging of Mesenchymal Stem Cell Transplant by Bioluminescence and PET

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.

Performance of a PSPMT based detector for scintimammography

In breast scintigraphy, compact detectors with high intrinsic spatial resolution and small inactive peripheries can provide improvements in extrinsic spatial resolution, efficiency and contrast for small lesions relative to larger conventional cameras. We are developing a pixelated small field-of-view gamma camera for scintimammography. Extensive measurements of the imaging properties of a prototype system have been made, including spatial resolution, sensitivity, uniformity of response, geometric linearity and energy resolution. An anthropomorphic torso phantom providing a realistic breast exit gamma spectrum has been used in a qualitative study of lesion detectability. A new type of breast imaging system that combines scintimammography and digital mammography in a single upright unit has also been developed. The system provides automatic co-registration between the scintigram and the digital mammogram, obtained with the breast in a single configuration. Intrinsic spatial resolution was evaluated via calculation of the phase-dependent modulation transfer function (MTF). Measurements of extrinsic spatial resolution, sensitivity and uniformity of response were made for two types of parallel hole collimator using NEMA (National Electrical Manufacturers Association) protocols. Geometric linearity was quantified using a line input and least squares analysis of the measured line shape. Energy resolution was measured for seven different crystal types, and the effectiveness of optical grease coupling was assessed. Exit gamma spectra were obtained using a cadmium zinc telluride based spectrometer. These were used to identify appropriate radioisotope concentrations for the various regions of an anthropomorphic torso phantom, such that realistic scatter conditions could be obtained during phantom measurements. For prone scintimammography, a special imaging table was constructed that permits simultaneous imaging of both breasts, as well as craniocaudal views. A dedicated breast imaging system was also developed that permits simultaneous acquisition and superposition of planar gamma images and digital x-ray images. The intrinsic MTF is nonstationary, and is dependent on the phase relationship between the signal and the crystal array matrix. Averaged over all phases, the MTF is approximately 0.75, 0.57 and 0.40 at spatial frequencies of 1.0, 1.5 and 2.0 cycles per cm, respectively. The phase averaged line spread function (LSF) has a FWHM value of 2.6 mm. Following uniformity corrections, the RMS deviations in flood images are only slightly greater than is predicted from counting statistics. Across an 80 mm section of the active area, the differential linearity is 0.83 mm and the absolute linearity 2.0 mm. Using an anthropomorphic torso phantom with detachable breasts, scatter radiation similar to that observed exiting the breast of scintimammography patients was observed. It was observed that scattered gamma rays can constitute the majority of the radiation incident on the detector, but that the scatter-to-primary ratio varies significantly across the field of view, being greatest in the caudal portion of the breast, where scatter from the liver is high. Using a lesion-to-breast concentration ratio of 6:1, a 1.0 cm3 simulated breast lesion was detectable in lateral images obtained with both the developmental camera and with a clinical camera, while a 0.35 cm3 lesion was detectable in neither. Utilization of the dual x-ray transmission, gamma emission breast imaging system greatly increases the conspicuity of scintimammographic lesions relative to prone imaging, as well as greatly facilitating the localization and identification of structures in the gamma image. The prototype imaging gamma detector exhibits spatial resolution superior to that of conventional cameras, and comparable uniformity of response and geometric linearity. Because of light losses in the crystals, the energy resolution is inferior to that of single crystal NaI(Tl) came

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.

Optimizing pinhole and parallel hole collimation for scintimammography with compact pixellated detectors

The relative resolution and sensitivity advantages of pinhole and parallel hole collimators for planar scintimammography with compact, pixellated gamma detectors were investigated using analytic models. Collimator design was studied as follows. A desired object resolution was specified for a pixellated detector with a given crystal size and intrinsic spatial resolution and for a given object-to-collimator distance. Using analytic formulas, pinhole and parallel hole collimator parameters were calculated that satisfy this object resolution with optimal geometric sensitivity. Analyses were performed for 15 cm /spl times/ 20 cm field of view detectors with crystal elements 1.0, 2.0, and 3.0 mm on a side and 140 keV incident photons. The sensitivity for a given object resolution was greater for pinhole collimation at smaller distances, as expected. The object distance at which the pinhole and parallel hole sensitivity curves cross each other is important. The crossover distances increased with larger crystal size for a constant object resolution and increased as the desired object resolution decreased for a constant crystal size. For example, for 4 mm object resolution and a pinhole collimator with focal length 13 cm, these distances were 5.5 cm, 6.5 cm, and 8 cm for the 1 mm, 2 mm, and 3 mm crystal detectors, respectively. The results suggest a strategy of parallel hole collimation for whole breast imaging and pinhole collimation for imaging focal uptake. This could be accomplished with a dual detector system with a different collimator type on each head or a single head system equipped with two collimators and a rapid switching mechanism.

Development of an application specific scintimammography detector based on a crystal scintillator array and a PSPMT

Abstract We report the results of studies conducted with small field of view scintimammography camera based on a position-sensitive photomultiplier tube (5″ Hamamatsu R3292) and several pixelized crystal scintillator arrays made of YAP, CsI(Na) and NaI(Tl) scintillators. Laboratory tests and pre-clinical phantom studies were conducted to compare and optimize the performances of the prototypes with special emphasis on spatial resolution (∼2–3xa0mm) and sufficient energy resolution for scatter rejection.

Performance Evaluation of a Dedicated Camera Suitable for Dynamic Radiopharmaceuticals Evaluation in Small Animals

As the result of a collaboration between the Detector and Imaging Group of Thomas Jefferson National Accelerator Facility (US), the Institute of Radioisotopes and Radiodiagnostic Products (IRRP) of N.C.S.R. ldquoDemokritosrdquo and the Biomedical Simulations and Imaging Applications Laboratory (BIOSIM) of National Technical University of Athens (Greece), a mouse sized camera optimized for Tc99m imaging was developed. The detector was built in Jefferson Lab and transferred to Greece, where it was evaluated with phantoms and small animals. The system will be used initially for planar dynamic studies in small animals, in order to assess the performance of new radiolabeled biomolecules for oncological studies. The active area of the detector is approximately 48 mm times 96 mm. It is based on two flat-panel Hamamatsu H8500 position sensitive photomultiplier tubes (PSPMT), a pixelated NaI(Tl) scintillator and a high resolution lead parallel-hole collimator. The system was developed to optimize both sensitivity and resolution for in vivo imaging of small animals injected with technetium compounds. The results of system evaluation in planar mode with phantoms are reported. Results are presented for in vivo dynamic studies of mice injected with > 100 muCi of two conventional and novel radiopharmaceuticals, namely Tc99m-MDP and Tc99m -Bombesin.

Design of compact pinhole SPECT system based on flat panel PMT

The present development of new gamma imagers has allowed to realize detectors with ultra high spatial resolution and very compact size for PET as well as for SPET application. In this paper we analyze and discuss the possible design of new pinhole SPECT scanners based on heads which consist of flat panel PSPMT and different design of scintillation arrays like NaI(Tl), 1 mm pixel size, and CsI(Tl) multi layers array, mounted in off centered configuration to improve the intrinsic spatial resolution of the imagers. The results show that an array configuration 2/spl times/2 Hamamatsu flat panel PSPMTs coupled to NaI(Tl) scintillation array with 1 mm pixel size, represents the best trade off between compactness and spatial resolution of pinhole SPET scanner. The use of off centered CsI(Tl) scintillation array coupled to a single flat panel PSPMT allows to arrange a high sensitivity and very compact pinhole SPET scanner at very low cost only worsening of 50% spatial resolution than an Anger gamma camera pinhole SPECT.

Analysis of factors affecting positron emission mammography (PEM) image formation

Image reconstruction for positron emission mammography (PEM) with the breast positioned between two parallel, planar detectors is usually performed by backprojection to image planes. Three important factors affecting PEM image reconstruction by backprojection are investigated: 1) image uniformity (flood) corrections, 2) image sampling (pixel size) and 3) count allocation methods. An analytic expression for uniformity correction is developed that incorporates factors for spatial-dependent detector sensitivity and geometric effects from acceptance angle limits on coincidence events. There is good agreement between experimental floods from a PEM system with a pixellated detector and numerical simulations. The analytic uniformity corrections are successfully applied to image reconstruction of compressed breast phantoms and reduce the necessity for flood scans at different image planes. Experimental and simulated compressed breast phantom studies show that lesion contrast is improved when the image pixel size is half of, rather than equal to, the detector pixel size, though this occurs at the expense of some additional image noise. In PEM reconstruction counts usually are allocated to the pixel in the image plane intersected by the line of response (LOR) between the centers of the detection pixels. An alternate count allocation method is investigated that distributes counts to image pixels in proportion to the area of the tube of response (TOR) connecting the detection pixels that they overlay in the image plane. This TOR method eliminates some image artifacts that occur with the LOR method and increases tumor signal-to-noise ratios at the expense of a slight decrease in tumor contrast. Analysis of image uniformity, image sampling and count allocation methods in PEM image reconstruction points to ways of improving image formation. Further work is required to optimize image reconstruction parameters for particular detection or quantitation tasks.