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.
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 3-D 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.
A room size PET scanner for neuroscience research is proposed in which subjects can move about freely in a natural environment. This scanner, termed RoomPET, would open new frontiers in the study of dynamic brain function. The key to a feasible system is PET detectors with a limited vertical dimension that may translate up and down to keep the brain in the field of view. Head position can be tracked by an array of video cameras, providing real-time data to guide detector motion and for motion-corrected image reconstruction. For a point in the center of the room and centered within the vertical field of view of the detectors, geometric sensitivity ranges between 4 and 18% for room widths of 2 to 3 m and detectors with vertical dimensions of 15 to 40 cm. Spatial resolution is dominated by annihilation photon non-colinearity due to the large detector separation. This non-colinearity contribution for F-18 is 4.4 and 6.6 mm full width at half maximum (FWHM) at the center of 2 ×2 and 3×3m 2 rooms, respectively, for a line of response orthogonal to the opposite walls. With pixelated scintillation crystal elements 2 mm on a side the system resolution for F-18 radiotracers is estimated at 4.5 and 6.7 mm FWHM for room widths of 2 and 3 m, respectively. A RoomPET system would advance the understanding of brain function in healthy humans and in those with neurological diseases, disorders and brain injury.
Investigating human brain function in response to environmental stimuli requires freely moving humans without attached instrumentation. The RoomPET concept provides a feasible solution for human brain imaging. A RoomPET system is a room that contains an optical head tracking system and PET detectors that move to keep the head in the PET detector field-of-view. As a proof of principle, a small box-size prototype was built to demonstrate feasibility of RoomPET with gantry mechanics, tracking capabilities, and control systems.
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.
The kinetics of single photon emitting macromolecules (e.g. antibodies) are typically slower than small molecules, necessitating long or repeat acquisitions. We previously proposed the use of motion tracking and limited angle tomographic reconstruction to characterise tracer kinetics over extended periods in awake rodents. In this study, we explored this approach by imaging a contrast phantom, moved with 6 degrees of freedom, using a prototype preclinical SPECT scanner with parallel-hole collimation and a fixed detector located at 0 and 90 degrees. The position of the phantom was tracked and data were acquired in list mode. Each event was motion corrected and reconstructed using LM-MLEM. Planar projections were created by summing the reconstructed volume along the x-axis. Line profiles of the contrast phantom were compared for a planar reference projection and projections generated from the motion-free, motion-corrupted and motion corrected reconstructions. Projections created from the motion corrected agreed well with the planar reference projection of the stationary object and exhibited similar contrast. Whilst this initial study was limited to rigid motion, it demonstrates the feasibility of motion-corrected planar projections of a moving object.
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 99mTc-pertechnetate phantom, 99mTc-methylene diphosphonate bone imaging, and measurement of the binding potential of the dopamine transporter radioligand 123I-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 123I-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.
A key feature of silicon photomultipliers (SiPMs) that can hinder their wider use in medium and high energy physics applications is their relatively high sensitivity to high energy background radiation, with particular regard to high energy neutrons. Dosages of 10(10) n(eq)/cm(2) can damage them severely. In this study, some standard versions along with some new formulations are irradiated with a high intensity (AmBe)-Am-241 source up to a total dose of 5 x 10(9) n(eq)/cm(2). Key parameters monitored include dark noise, photon detection efficiency (PDE), gain, and voltage breakdown. Only dark noise was found to change significantly for this range of dosage. Analysis of the data indicates that within each vendor's product line, the change in dark noise is very similar as a function of increasing dose. At present, the best strategy for alleviating the effects of radiation damage is to cool the devices to minimize the effects of increased dark noise with accumulated dose.
The main objective of the present study was to determine if combining the two images from a conjugate counting system might improve the contrast and signal-to-noise ratio (SNR) of small lesions in all regions of the breast compared to images from a single camera. Several methods for combining the opposing pixels of the two camera images were compared: multiplication, geometric mean, and summation. The image quality metrics measured were spatial resolution, lesion contrast and lesion SNR. These quantities were evaluated both theoretically and experimentally. A capillary phantom was used to measure the spatial resolution as a function of lesion depth and to assess the translation and angular offsets between the two cameras. An acrylic box phantom, with spherical lesions suspended inside, was used to evaluate contrast and SNR as a function of lesion position. Both theoretically and experimentally the spatial resolution in the product images was superior to that in the single images, geometric mean or summation images. Relative to the single camera images, the geometric mean or the summed images, the lesion contrast and SNR of the product images were superior, irrespective of lesion depth, and were more constant with changing lesion depth compared to the single camera images. These findings suggest that improved lesion detectability is possible by imaging simultaneously from both sides of the breast, and forming a combined image using pixel-by-pixel multiplication. This may be especially important if the location of the lesion within the breast is not known a priori.
Positron Emission Tomography (PET) historically has major clinical and preclinical applications in cancerous oncology, neurology, and cardiovascular diseases. Recently, in a new direction, an application specific PET system is being developed at Thomas Jefferson National Accelerator Facility (Jefferson Lab) in collaboration with Duke University, University of Maryland at Baltimore (UMAB), and West Virginia University (WVU) targeted for plant eco-physiology research. The new plant imaging PET system is versatile and scalable such that it could adapt to several plant imaging needs - imaging many important plant organs including leaves, roots, and stems. The mechanical arrangement of the detectors is designed to accommodate the unpredictable and random distribution in space of the plant organs without requiring the plant be disturbed. Prototyping such a system requires a new data acquisition system (DAQ) and data processing system which are adaptable to the requirements of these unique and versatile detectors.
While nuclear methods find application in plant biology there are very limited amount of instrumentation that is geared to the unique challenges that plant biology presents. Mostly researchers are utilizing devices created for clinical and preclinical imaging. The majority of the biologically significant elements involved in plant formation have positron emitting isotopes, making positron emission tomography a naturally fitting imaging modality. One particular caveat in using PET instrumentation in plant imaging is extremely small thickness of the leaf as an annihilation medium for emitted positrons. For positron energies around 1 MeV (as in case of C-11), about 1 mm of water equivalent material is required for positron conversion, so most of the positrons would not annihilate inside the leaf, therefore limiting both sensitivity and spatial resolution of the imaging system. In this work we made an attempt of determining whether direct imaging of positrons could be beneficial in plant biology studies. We compared performance of direct positron detector with a planar PET system. Detection efficiency ratio of ~650 in favor of direct positron detection system was measured. Direct comparison of spatial resolutions yielded comparable numbers for a setup, when a phantom was placed directly onto the entrance window of the positron detector. We also determined quick deterioration of spatial resolution as a function of source to detector distance. The last observation makes it necessary to maintain close proximity of the object to the detector, but this condition can be met in plant biology study.
We have developed a novel approach that allows for fast estimation of margins of extracted lesions. Dual modality planar optical/PET scanner consists of a pair of detector heads, suitable for imaging positron-emitting radioisotopes, a mechanical fixture to maintain constant separation between the two cameras, an optical camera that provides an anatomical map, a sliding table with an attached sample holder and a common mobile gantry that supports all of the system components. The two identical detector heads are based on a 4×4 array of Hamamatsu R5900-C-8 position-sensitive photomultiplier tubes (PSPMTs) with 4 strip anodes in each orthogonal dimension. Each tube has an active region of ∼1 inch square. The PSPMT array is coupled to a matrix of LGSO scintillating crystals; with each crystal measuring 3×3×10 mm. The active area of the PET subsystem is 10 cm square. Anode readout strips are interconnected to provide 8 read-out lines for each dimension of the detector head. Detector heads are read out by a custom-built 16-channel FPGA-based ADC. Online laminography reconstruction is performed over five parallel planes, separated by a selectable distance, and images from each plane can be directly exported into an ImageJ software package for overlay and further analysis. System calibration process is described. Results of imaging of several tissue simulating materials are presented. The ability of the proposed dual-modality scanner to detect lesions in warm background has been demonstrated. Although the proposed system will not eliminate the need for pathology analysis, it will help to reduce time in surgery by unveiling insufficient margins in the sample tissue. The system will be soon demonstrated and tested in a realistic clinical environment.
We are developing a breast scanner that obtains co-registered dual modality tomographic images of the breast using x-ray imaging (digital breast tomosynthesis) and gamma emission imaging (limited angle breast SPECT). The project is a collaborative effort among the Jefferson Lab (Newport News, VA), Dexela Ltd., (Sudbury MA), and the University of Virginia (UVa) (Charlottesville, VA). The scanner is currently undergoing pilot clinical evaluation at UVa’s Breast Care Center. Here we report on the design of the scanner, choice of acquisition parameters, and present some early phantom and human breast images.
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 multiprocessor 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 mu Ci(-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.
The goal of this study was to evaluate the efficacy of operating a two-head gamma camera system in a configuration in which the two cameras are positioned on opposite sides of the compressed breast, aligned precisely with each other and with precisely anti-parallel viewing directions. The main objective of the present study was to determine if the combination of the two resulting images might allow for better sensitivity for small lesions in all regions of the breast. Two pairs of gamma cameras were evaluated; one composed of commercially available gamma cameras and the other composed of two research-based gamma cameras. For each pair, an acrylic box phantom, with two spherical lesions suspended inside, was used to evaluate contrast and SNR as a function of lesion position, first for images from the two cameras separately and then for images obtained from pixel- by-pixel multiplication or summation of the individual images. A capillary phantom was used to quantify the spatial resolution as a function of lesion depth for the cameras individually as well as for the resulting multiplied images. Lastly, gelatin phantoms were imaged, each containing a single cube-shaped lesion of ~8 mm side length positioned at varying depths within the phantom. Relative to the single camera images or the summed images, the lesion contrast and SNR of the multiplication image were superior, irrespective of lesion depth, and were much more constant with changing lesion depth. Except when the lesion was less than a centimeter from one of the cameras, the SNR of the multiplied image exceeded that of a single camera image obtained using twice the acquisition time. These findings suggest that improved lesion detectability is possible by imaging simultaneously from both sides of the breast, especially if the location of the lesion within the breast is not known a priori.
Performance of a new XP1470 nine-channel photomultiplier tube was studied for economical yet high resolution single gamma and PET imaging applications. Four samples of this PMT were tested using two different front-end readout schemes. Spatial and time resolution performance of 1 times 2 and 2 times 2 array configurations of these PMTs were studied with 2 mm and 3 mm pixellated LYSO and Nal(Tl) crystal arrays with 122 keV and 511 keV gamma rays. With optimized light spreader, good pixel separation and good energy resolution were achieved in a small ~10 times 10 cm 2 active FOV PET or single gamma detector module prototype.