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.

Experimental validation of a rodent PET scanner prototype based on a single LYSO crystal tube.

Improving sensitivity and spatial resolution in small animal Positron Emission Tomography imaging instrumentation constitutes one of the main goals of nuclear imaging research. These parameters are degraded by the presence of gaps between the detectors. The present manuscript experimentally validates our prototype of an edge-less pre-clinical PET system based on a single LYSO:Ce annulus with an inner diameter of 62 mm and 10 outer facets of 26 × 52 mm2. Scintillation light is read out by arrays of 8 × 8 SiPMs coupled to the facets, using a projection readout of the rows and columns signals. The readout provides accurate Depth of Interaction (DOI). We have implemented a calibration that mitigates the DOI-dependency of the transaxial and axial impact coordinates, and the energy photopeak gain. An energy resolution of 23.4 ± 1.8% was determined. Average spatial resolution of 1.4 ± 0.2 and 1.3 ± 0.4 mm FWHM were achieved for the radial and axial directions, respectively. We found a peak sensitivity of 3.8% at the system center, and a maximum NECR at 40.6 kcps for 0.27 mCi. The image quality was evaluated using reconstructed images of an array of sources and the NEMA image quality phantom was also studied.

Performance comparison of a dedicated total breast PET system with a clinical whole-body PET system: a simulation study.

This paper presents a novel PET geometry for breast cancer imaging. The scanner consists of a 'stadium' (a rectangle with two semi-circles on opposite sides) shaped ring, along with anterior and posterior panels to provide high sensitivity and high spatial resolution for an imaging field-of-view (FOV) that include both breasts, mediastinum and axilla. We simulated this total-breast PET system using GATE and reconstructed the coincidence events using a GPU-based list-mode image reconstruction implementing maximum likelihood expectation-maximization (ML-EM) algorithm. The rear-panel is made up of a single layer of LSO crystals (3.2 × 3.2 × 20 mm3each), while the 'stadium'-shaped elongated ring and the anterior panel are made with dual-layered LSO crystals (1.6 × 1.6 × 6 mm3each). The energy resolution and coincidence resolving time of all detectors are assumed to be 12% and 250 ps full-width-at-half-maximum, respectively. Various sized simulated lesions (4, 5, 6 mm) having 4:1, 5:1, and 6:1 lesion-to-background radioactivity concentration ratios, mimicking different biological uptakes, were strategically located throughout a volumetric torso phantom. We compared system sensitivity and lesion detectability of the dedicated total-breast PET system to a state-of-the-art clinical whole-body PET scanner. The mean sensitivity of the total-breast PET system is 3.21 times greater than that of a whole-body PET scanner in the breast regions. The total-breast PET system also provides better contrast-recovery coefficients for lesions of all sizes and lesion-to-background ratios in the breast when compared to a reference clinical whole-body PET scanner. Receiver operating characteristics (ROC) study shows the area under the ROC curve is 0.948 and 0.924 for the total-breast system and the whole-body PET scanner, respectively, in the detection of 4 mm diameter lesions with 4:1 lesion-to-background ratio. This study demonstrates our novel geometry can provide an imaging FOV larger than conventional PEM systems to simultaneously image both breasts, chest wall and axillae with significantly improved lesion detectability in the breasts when compared to a whole-body PET scanner.

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.

Do women with dense breasts have higher radiation dose during screening mammography?

Radiation dose during screening mammography is a concern among women. The purpose of this study was to evaluate the relative contribution of breast density to the radiation dose from screening mammography. This IRB approved retrospective study involved collecting patient age, weight, height, compressed breast thickness, and average glandular dose for each exposure for 434 sequential patients undergoing screening mammography at our institution. Automated volumetric density software was used to quantify breast density. The relationship of predictors was evaluated by univariate and multivariate analysis. Median patient age was 58 years and median body mass index (BMI) was 26.8. Median volumetric breast density was 5.8% (range 1.7-30.5%). Median compressed breast thickness was 63.4 mm (range 24.5-111.5 mm). Univariate analysis showed positive associations between radiation dose and both breast thickness and BMI, an inverse association with age, and no association with density. Multivariate regression analysis demonstrated a significant association between dose and age (P=.021), laterality (P<.001), BMI (P=.038), density (P<.001), and breast thickness (P<.001). Decomposition of the multivariate regression model coefficient of determination showed that breast thickness was the primary determinant of dose, accounting for 76% of the 58% of the dose variability, followed by density (8%), laterality (4%), age (<1%), and BMI (<1%). Compressed breast thickness had the greatest effect on average glandular dose. Breast density has a minor impact, while BMI and age have minimal impact on dose.

Effects on image quality of a 2D antiscatter grid in x-ray digital breast tomosynthesis: Initial experience using the dual modality (x-ray and molecular) breast tomosynthesis scanner.

PURPOSE: Radiation scattered from the breast in digital breast tomosynthesis (DBT) causes image degradation, including loss of contrast between cancerous and background tissue. Unlike in 2-dimensional (2D) mammography, an antiscatter grid cannot readily be used in DBT because changing alignment between the tube and detector during the scan would result in unacceptable loss of primary radiation. However, in the dual modality breast tomosynthesis (DMT) scanner, which combines DBT and molecular breast tomosynthesis, the tube and detector rotate around a common axis, thereby maintaining a fixed tube-detector alignment. This C-arm geometry raises the possibility of using a 2D (cellular) focused antiscatter grid. The purpose of this study is to assess change in image quality when using an antiscatter grid in the DBT portion of a DMT scan under conditions of fixed radiation dose. METHODS: Two 2D focused prototype grids with 80 cm focal length were tested, one stack-laminated from copper (Cu) and one cast from a tungsten-polymer (W-poly). They were reciprocated using a motion scheme designed to maximize transmission of primary x-ray photons. Grid-in and grid-out scatter-to-primary ratios (SPRs) were measured for rectangular blocks of material simulating 30%, 50%, and 70% glandular tissue compositions. For assessment of changes in image quality through the addition of a grid, the Computerized Imaging Reference Systems, Inc., phantom Model 011A containing a set of 1 cm thick blocks simulating a range of glandular/adipose ratios from 0/100 to 100/0 was used. To simulate 6.5 and 8.5 cm thick compressed breasts, 1 cm thick slices of PMMA were added to the Model 011A phantom. DBT images were obtained with and without the grid, with exposure parameters fixed for a given compressed thickness. Signal-difference-to-noise ratios (SDNRs), contrast, and voxel value-based attenuation coefficients (µ) were measured for all blocks from reconstructed phantom images. RESULTS: For 4, 6, and 8 cm tissue-equivalent block phantom thicknesses, the inclusion of the W-poly grid reduced the SPR by factors of 5, 6, and 5.8, respectively. For the same thicknesses, the copper grid reduced the SPR by factors of 3.9, 4.5, and 4.9. For the 011A phantom, the W-poly grid raised the SDNR of the 70/30 block from 0.8, -0.32, and -0.72 to 0.9, 0.76, and 0.062 for the 4.5, 6.5, and 8.5 cm phantoms, respectively. It raised the SDNR of the 100/0 block from 3.78, 1.95, and 1.0 to 3.79, 3.67, and 3.25 for the 4.5, 6.5, and 8.5 cm phantoms, respectively. Inclusion of the W-poly grid improved the accuracy of image-based µ values for all block compositions. However, smearing of attenuation across slices due to limited angular sampling decreases the sensitivity of voxel values to changing composition compared to theoretical µ values. CONCLUSIONS: Under conditions of fixed radiation dose to the breast, use of a 2D focused grid increased contrast, SDNR, and accuracy of estimated attenuation for mass-simulating block compositions in all phantom thicknesses tested, with the degree of improvement depending upon material composition. A 2D antiscatter grid can be usefully incorporated in DBT systems that employ fully isocentric tube-detector rotation.

Design and characterization of a low profile NaI(Tl) gamma camera for dedicated molecular breast tomosynthesis.

A new low profile gamma camera is being developed for use in a dual modality (x-ray transmission and gamma-ray emission) tomosynthesis system. Compared to the system's current gamma camera, the new camera has a larger field of view (~20×25 cm) to better match the system's x-ray detector (~23×29 cm), and is thinner (7.3 cm instead of 10.3 cm) permitting easier camera positioning near the top surface of the breast. It contains a pixelated NaI(Tl) array with a crystal pitch of 2.2 mm, which is optically coupled to a 4×5 array of Hamamatsu H8500C position sensitive photomultiplier tubes (PSPMTs). The manufacturer-provided connector board of each PSPMT was replaced with a custom designed board that a) reduces the 64 channel readout of the 8×8 electrode anode of the H8500C to 16 channels (8X and 8Y), b) performs gain non-uniformity correction, and c) reduces the height of the PSPMT-base assembly, 37.7 mm to 27.87 mm. The X and Y outputs of each module are connected in a lattice framework, and at two edges of this lattice, the X and Y outputs (32Y by 40X) are coupled to an amplifier/output board whose signals are fed via shielded ribbon cables to external ADCs. The camera uses parallel hole collimation. We describe the measured camera imaging performance, including intrinsic and extrinsic spatial resolution, detection sensitivity, uniformity of response, energy resolution for 140 keV gamma rays, and geometric linearity.

Design and evaluation of a grid reciprocation scheme for use in digital breast tomosynthesis.

This work describes a methodology for efficient removal of scatter radiation during digital breast tomosynthesis (DBT). The goal of this approach is to enable grid image obscuration without a large increase in radiation dose by minimizing misalignment of the grid focal point (GFP) and x-ray focal spot (XFS) during grid reciprocation. Hardware for the motion scheme was built and tested on the dual modality breast tomosynthesis (DMT) scanner, which combines DBT and molecular breast tomosynthesis (MBT) on a single gantry. The DMT scanner uses fully isocentric rotation of tube and x-ray detector for maintaining a fixed tube-detector alignment during DBT imaging. A cellular focused copper prototype grid with 80 cm focal length, 3.85 mm height, 0.1 mm thick lamellae, and 1.1 mm hole pitch was tested. Primary transmission of the grid at 28 kV tube voltage was on average 74% with the grid stationary and aligned for maximum transmission. It fell to 72% during grid reciprocation by the proposed method. Residual grid line artifacts (GLAs) in projection views and reconstructed DBT images are characterized and methods for reducing the visibility of GLAs in the reconstructed volume through projection image flat-field correction and spatial frequency-based filtering of the DBT slices are described and evaluated. The software correction methods reduce the visibility of these artifacts in the reconstructed volume, making them imperceptible both in the reconstructed DBT images and their Fourier transforms.

Comparison of breast specific gamma imaging and molecular breast tomosynthesis in breast cancer detection: Evaluation in phantoms.

PURPOSE: Breast specific gamma imaging or molecular breast imaging (BSGI) obtains 2D images of (99m)Tc sestamibi distribution in the breast. Molecular breast tomosynthesis (MBT) maps the tracer distribution in 3D by acquiring multiple projections over a limited angular range. Here, the authors compare the performance of the two technologies in terms of spatial resolution, lesion contrast, and contrast-to-noise ratio (CNR) in phantom studies under conditions of clinically relevant sestamibi dose and imaging time. METHODS: The systems tested were a Dilon 6800 and a MBT prototype developed at the University of Virginia. Both systems comprise a pixelated sodium iodide scintillator, an array of position sensitive photomultipliers, and a parallel hole collimator. The active areas and energy resolution of the systems are similar. System sensitivity, spatial resolution, lesion contrast, and CNR were measured using a Petri dish, a point source phantom, and a breast phantom containing simulated lesions at two depths, respectively. A single BSGI projection was acquired. Five MBT projections were acquired over ±20°. For both modalities, the total scan count density was comparable to that observed for each in typical 10 min human scans following injection of 22 mCi (814 MBq) of (99m)Tc-sestamibi. To assess the impact of reducing the tracer dose, the pixel counts of projection images were later binomially subsampled by a factor of 2 to give images corresponding to an injected activity of approximately 11 mCi (407 MBq). Both unprocessed (pixelated) BSGI projections and interpolated (smoothed) BSGI images displayed by default on the Dilon 6800 workstation were analyzed. Volumetric images were reconstructed from the MBT projections using a maximum likelihood expectation maximization algorithm and extracted slices were analyzed. RESULTS: Over a depth range of 1.5-7.5 cm, BSGI spatial resolution was 5.6-11.5 mm in unprocessed projections and 5.7-12.0 mm in interpolated images. Over the same range, the in-slice MBT spatial resolution was 6.7-9.4 mm. Lesion contrast was significantly improved with MBT relative to BSGI for five out of eight lesions imaged at either the 22 mCi or the 11 mCi dose level (p < 0.05). At both dose levels, significant improvements in CNR with MBT were also found for five out of eight lesions (9.8, 7.8, 6.2 mm lesions at water depth of 1.7 cm and 9.8, 7.8 mm lesions at water depth of 4.5 cm, p < 0.05). The 6.2 and 4.9 mm lesions located at 4.5 cm below the water surface were not visible in either modality at either activity level. CONCLUSIONS: Under conditions of equal dose, imaging time and similar detectors, compared to BSGI, MBT provided higher lesion contrast, higher CNR, and spatial resolution that was less depth dependent.

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.

Novel cancer-targeting SPECT/NIRF dual-modality imaging probe (99m)Tc-PC-1007: synthesis and biological evaluation.

Synthesis, characterization, in vitro and in vivo biological evaluation of a heptamethine cyanine based dual-mode single-photon emission computed tomography (SPECT)/near infrared fluorescence (NIRF) imaging probe (99m)Tc-PC-1007 is described. (99m)Tc-PC-1007 exhibited preferential accumulation in human breast cancer MCF-7 cells. Cancer-specific SPECT/CT and NIRF imaging of (99m)Tc-PC-1007 was performed in a breast cancer xenograft model. The probe uptake ratio of tumor to control (spinal cord) was calculated to be 4.02±0.56 at 6 h post injection (pi) and 8.50±1.41 at 20 h pi (P<0.0001). Pharmacokinetic parameters such as blood clearance and organ distribution were assessed.

Implementation and evaluation of an expectation maximization reconstruction algorithm for gamma emission breast tomosynthesis.

PURPOSE: We are developing a dual modality tomosynthesis breast scanner in which x-ray transmission tomosynthesis and gamma emission tomosynthesis are performed sequentially with the breast in a common configuration. In both modalities projection data are obtained over an angular range of less than 180° from one side of the mildly compressed breast resulting in incomplete and asymmetrical sampling. The objective of this work is to implement and evaluate a maximum likelihood expectation maximization (MLEM) reconstruction algorithm for gamma emission breast tomosynthesis (GEBT). METHODS: A combination of Monte Carlo simulations and phantom experiments was used to test the MLEM algorithm for GEBT. The algorithm utilizes prior information obtained from the x-ray breast tomosynthesis scan to partially compensate for the incomplete angular sampling and to perform attenuation correction (AC) and resolution recovery (RR). System spatial resolution, image artifacts, lesion contrast, and signal to noise ratio (SNR) were measured as image quality figures of merit. To test the robustness of the reconstruction algorithm and to assess the relative impacts of correction techniques with changing angular range, simulations and experiments were both performed using acquisition angular ranges of 45°, 90° and 135°. For comparison, a single projection containing the same total number of counts as the full GEBT scan was also obtained to simulate planar breast scintigraphy. RESULTS: The in-plane spatial resolution of the reconstructed GEBT images is independent of source position within the reconstructed volume and independent of acquisition angular range. For 45° acquisitions, spatial resolution in the depth dimension (the direction of breast compression) is degraded with increasing source depth (increasing distance from the collimator surface). Increasing the acquisition angular range from 45° to 135° both greatly reduces this depth dependence and improves the average depth dimension resolution from 10.8 to 4.8 mm. The 135° acquisition results in a near-isotropic, spatially uniform 3D resolution of approximately 4.3 mm full width at half maximum. Background nonuniformity (cupping) artifacts arise primarily from angular incompleteness for small angular range acquisition but primarily from gamma ray attenuation at larger angular range. However, background artifacts can be largely eliminated if both prior information regularization and AC are applied. An artificial decrease in lesion voxel value with increasing lesion depth can also be substantially reduced through a combination of AC and RR. In experiments using compressible gelatin breast phantoms, lesion contrast and SNR are about 2.6-8.8 times and 2.3-5.6 times higher, respectively, in GEBT than in planar breast scintigraphy depending on the acquisition angle, the gamma camera trajectory, and the lesion location. In addition, the strong reduction in lesion contrast and SNR with increasing lesion depth that is observed in planar breast scintigraphy can be largely overcome in GEBT. CONCLUSIONS: The authors have demonstrated a promising EM-based reconstruction scheme for use in GEBT. Compared to planar breast scintigraphy GEBT provides superior and less position-dependent lesion contrast, lesion SNR, and spatial resolution as well as more accurate quantification of lesion-to-background activity concentration ratio.

PET imaging of tumor associated macrophages using mannose coated 64Cu liposomes.

Macrophages within the tumor microenvironment (TAMs) have been shown to play a major role in the growth and spread of many types of cancer. Cancer cells produce cytokines that cause macrophages to express scavenger receptors (e.g. the mannose receptor) and factors that facilitate tissue and blood vessel growth, suppress T cell mediated anti-tumor activity, and express enzymes that can break down the extracellular matrix, thereby promoting metastasis. We have designed a mannosylated liposome (MAN-LIPs) and show that it accumulates in TAMs in a mouse model of pulmonary adenocarcinoma. These liposomes are loaded with (64)Cu to allow tracking by PET imaging, and contain a fluorescent dye in the lipid bilayer permitting subsequent fluorescence microscopy. We injected these liposomes into a mouse model of lung cancer. In vivo PET images were acquired 6 h after injection followed by the imaging of select excised organs. MAN-LIPs accumulated in TAMs and exhibited little accumulation in remote lung areas. MAN-LIPs are a promising new vehicle for the delivery of imaging agents to lung TAMs. In addition to imaging, MAN-LIPs hold the potential for delivery of therapeutic agents to the tumor microenvironment.

The Impact of Reduced Injected Radioactivity on Image Quality of Molecular Breast Imaging Tomosynthesis.

This study's objective is to compare image quality in 3-D molecular breast imaging tomosynthesis (MBIT) with that in planar molecular breast imaging (MBI) over a range of breast radioactivity concentrations. Using gelatin and point source phantoms lesion contrast, lesion signal-to-noise ratio (SNR) and spatial resolution were compared for a range of lesion sizes and depths. For both MBI and MBIT, lesion contrast is essentially constant with changing activity while SNR decreases by a factor of 1.5 - 2 between 100% and 25% activity levels. For nearly all lesion sizes and locations contrast and SNR are significantly higher for MBIT than MBI, potentially permitting greater reductions in injected dose. Spatial resolution in MBI is dependent on lesion depth but independent of lesion location with MBIT. Reconstructed MBIT spatial resolution is substantially better than that in the projection images, suggesting future use of higher sensitivity collimators for even further reductions in injected activity.

Detective Quantum Efficiency of a CsI-CMOS X-ray Detector for Breast Tomosynthesis Operating in High Dynamic Range and High Sensitivity Modes.

The spatial frequency dependent detective quantum efficiency (DQE) of a CsI-CMOS x-ray detector was measured in two operating modes: a high dynamic range (HDR) mode and a high sensitivity (HS) mode. DQE calculations were performed using the IEC-62220-1-2 Standard. For detector entrance air kerma values between ~7 µGy and 60 µGy the DQE is similar in either HDR mode or HS mode, with a value of ~0.7 at low frequency and ~ 0.15 - 0.20 at the Nyquist frequency fN = 6.7 mm-1. In HDR mode the DQE remains virtually constant for operation with Ka values between ~7 µGy and 119 µGy but decreases for Ka levels below ~ 7 µGy. In HS mode the DQE is approximately constant over the full range of entrance air kerma tested between 1.7 µGy and 60 µGy but kerma values above ~75 µGy produce hard saturation. Quantum limited operation in HS mode for entrance kerma as small as 1.7 µGy makes it possible to use a large number of low dose views to improve angular sampling and decrease acquisition time.

FDG-PET Quantification of Lung Inflammation with Image-Derived Blood Input Function in Mice.

Dynamic FDG-PET imaging was used to study inflammation in lungs of mice following administration of a virulent strain of Klebsiella (K.) pneumoniae. Net whole-lung FDG influx constant (K(i)) was determined in a compartment model using an image-derived blood input function. Methods. K. pneumoniae (~3 x 10(5) CFU) was intratracheally administered to six mice with 6 other mice serving as controls. Dynamic FDG-PET and X-Ray CT scans were acquired 24 hr after K. pneumoniae administration. The experimental lung time activity curves were fitted to a 3-compartment FDG model to obtain K(i). Following imaging, lungs were excised and immunohistochemistry analysis was done to assess the relative presence of neutrophils and macrophages. Results. Mean K(i) for control and K. pneumoniae infected mice were (5.1 ± 1.2) ×10(-3) versus (11.4 ± 2.0) ×10(-3) min(-1), respectively, revealing a 2.24 fold significant increase (P = 0.0003) in the rate of FDG uptake in the infected lung. Immunohistochemistry revealed that cellular lung infiltrate was almost exclusively neutrophils. Parametric K(i) maps by Patlak analysis revealed heterogeneous inflammatory foci within infected lungs. Conclusion. The kinetics of FDG uptake in the lungs of mice can be noninvasively quantified by PET with a 3-compartment model approach based on an image-derived input function.

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.

Neutrophil targeting heterobivalent SPECT imaging probe: cFLFLF-PEG-TKPPR-99mTc.

A new heterobivalent peptide ligand specifically targeting polymorphonuclear leukocytes (PMNs) with favorable pharmacological parameters to monitor sites of inflammation for imaging is designed. The detailed synthesis, characterization, and pharmacological evaluation of the ligands are reported here. Two separate peptide binding ligands for formyl peptide and tuftsin receptors were chosen to link together based on the high expression levels of the two receptors on activated PMNs The heterobivalency and pegylated links were incorporated in the structural design to improve the sensitivity of the detection and to improve the bioavailability along with blood clearance profile, respectively. Two chemical constructs, cFLFLF-(PEG)(n)-TKPPR-(99m)Tc (n = 4, 12), were evaluated in vitro with human PMNs for binding affinity and bioavailability. As a result, cFLFLF-(PEG)(12)-TKPPR-(99m)Tc was found to have more favorable pharmacological properties and was therefore used for further in vivo studies. Preliminary in vivo assessment of the agent was performed using single gamma emission computed tomography (SPECT) imaging of a mouse model of ear inflammation. The results of these studies indicate cFLFLF-(PEG)(12)-TKPPR-(99m)Tc may be a desirable imaging agent for binding to PMNs to identify sites of inflammation by SPECT.

Dual-modality breast tomosynthesis.

PURPOSE: To evaluate the clinical performance of a hybrid scanner that uses dual-modality tomosynthesis (DMT) and technetium 99m sestamibi to provide coregistered anatomic and functional breast images in three dimensions. MATERIALS AND METHODS: A prospective pilot evaluation of the scanner was performed in women scheduled to undergo breast biopsy after institutional review board approval and informed consent were obtained. All subject data were handled in compliance with the rules and regulations concerning the privacy and security of protected health information under HIPAA. The study included 17 women (mean age, 53 years; age range, 44-67 years) and 21 biopsy-sampled lesions. Results of DMT scanning were compared with histopathologic results for the 21 lesions. RESULTS: Of the 21 lesions, seven were malignant, and 14 were benign. Among the 13 subjects with one lesion each, three had positive biopsy results, and 10 had negative biopsy results. Among the four subjects with two lesions, the biopsy results were as follows: bilateral in one, both negative; bilateral in one, both positive; unilateral in two, one positive and one negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of DMT scanning were 86%, 100%, 100%, 93%, and 95%, respectively. CONCLUSION: Pilot clinical evaluation of the DMT scanner suggests that it is a feasible and accurate method with which to detect and diagnose breast cancer. Systems such as the DMT scanner that are designed specifically for three-dimensional multimodality breast imaging could make possible some of the advances in tumor detection, localization, and characterization of breast cancer that are now being observed with whole-body three-dimensional hybrid systems, such as positron emission tomography/computed tomography (CT) or single photon emission computed tomography/CT.