Anomaly Detection and Artifact Recovery in PET Attenuation-Correction Images Using the Likelihood Function.

In dual modality PET/CT, CT data are used to generate the attenuation correction applied in the reconstruction of the PET emission image. This requires converting the CT image into a 511-keV attenuation map. Algorithms for making this transformation require assumptions about the makeup of material within the patient. Anomalous material such as contrast agent administered to enhance the CT scan confounds conversion algorithms and has been observed to result in inaccuracies, i.e., inconsistencies with the true 511-keV attenuation present at the time of the PET emission scan. These attenuation artifacts carry through to the final attenuation-corrected PET emission image and can resemble diseased tissue. We propose an approach to correcting this problem that employs the attenuation information carried by the PET emission data. A likelihood-based algorithm for identifying and correcting of contrast is presented and tested. The algorithm exploits the fact that contrast artifacts manifest as too-high attenuation values in an otherwise high quality attenuation image. In a separate study, the performance of the loglikelihood as an objective-function component of a detection/correction algorithm, independent of any particular algorithm was mapped out for several imaging scenarios as a function of statistical noise. Both the full algorithm and the loglikelihood performed well in studies with simulated data. Additional studies including those with patient data are required to fully understand their capabilities.

Successful transplantation of human hepatic stem cells with restricted localization to liver using hyaluronan grafts.

Cell therapies are potential alternatives to organ transplantation for liver failure or dysfunction but are compromised by inefficient engraftment, cell dispersal to ectopic sites, and emboli formation. Grafting strategies have been devised for transplantation of human hepatic stem cells (hHpSCs) embedded into a mix of soluble signals and extracellular matrix biomaterials (hyaluronans, type III collagen, laminin) found in stem cell niches. The hHpSCs maintain a stable stem cell phenotype under the graft conditions. The grafts were transplanted into the livers of immunocompromised murine hosts with and without carbon tetrachloride treatment to assess the effects of quiescent versus injured liver conditions. Grafted cells remained localized to the livers, resulting in a larger bolus of engrafted cells in the host livers under quiescent conditions and with potential for more rapid expansion under injured liver conditions. By contrast, transplantation by direct injection or via a vascular route resulted in inefficient engraftment and cell dispersal to ectopic sites. Transplantation by grafting is proposed as a preferred strategy for cell therapies for solid organs such as the liver.

Target localization using scanner-acquired SPECT data.

Target localization using single photon emission computed tomography (SPECT) and planar imaging is being investigated for guiding radiation therapy delivery. Previous studies on SPECT-based localization have used computer-simulated or hybrid images with simulated tumors embedded in disease-free patient images where the tumor position is known and localization can be calculated directly. In the current study, localization was studied using scanner-acquired images. Five fillable spheres were placed in a whole body phantom. Sphere-to-background 99mTc radioactivity was 6:1. Ten independent SPECT scans were acquired with a Trionix Triad scanner using three detector trajectories: left lateral 180°, 360°, and right lateral 180°. Scan time was equivalent to 4.5 min. Images were reconstructed with and without attenuation correction. True target locations were estimated from 12 hr SPECT and CT images. From the 12 hr SPECT scan, 45 sets of orthogonal planar images were used to assess target localization; total acquisition time per set was equivalent to 4.5min. A numerical observer localized the center of the targets in the 4.5 min SPECT and planar images. SPECT-based localization errors were compared for the different detector trajectories. Across the four peripheral spheres, and using optimal iteration numbers and postreconstruction smoothing, means and standard deviations in localization errors were 0.90 ± 0.25 mm for proximal 180° trajectories, 1.31 ± 0.51 mm for 360° orbits, and 3.93 ± 1.48 mm for distal 180° trajectories. This rank order in localization performance is predicted by target attenuation and distance from the target to the collimator. For the targets with mean localization errors < 2 mm, attenuation correction reduced localization errors by 0.15 mm on average. The improvement from attenuation correction was 1.0 mm on average for the more poorly localized targets. Attenuation correction typically reduced localization errors, but for well-localized targets, the detector trajectory generally had a larger effect. Localization performance was found to be robust to iteration number and smoothing. Localization was generally worse using planar images as compared with proximal 180° and 360° SPECT scans. Using a proximal detector trajectory and attenuation correction, localization errors were within 2 mm for the three superficial targets, thus supporting the current role in biopsy and surgery, and demonstrating the potential for SPECT imaging inside radiation therapy treatment rooms.

Combination of converging collimators for high-sensitivity brain SPECT.

UNLABELLED: The objective of this study, which is related to human brain SPECT, was to increase the sensitivity of a triple-camera SPECT system and reduce statistical noise in reconstructed images using a combination of converging collimators. The reason for combining collimators is to ensure both high sensitivity and sufficient sampling without trading off spatial resolution. METHODS: A high-sensitivity half-cone-beam (HCB) collimator, designed specifically for brain imaging, was combined with other collimators and compared with conventional parallel-beam and fanbeam circular orbit acquisitions. For comparison, previously studied HCB collimation with a circle-and-helix data acquisition trajectory was also included in this study. Simulations of the Hoffman 3-dimensional brain phantom were performed to calculate the efficiencies of collimators and their combinations and to quantitatively evaluate reconstruction bias, statistical noise, and signal-to-noise ratios in the reconstructed images. Experimental brain phantom data were also acquired and compared for different acquisition types. Finally, a patient brain scan was obtained with a combination of HCB and fanbeam collimators and compared with a triple-fanbeam circular orbit acquisition. RESULTS: A combination of 2 HCB collimators and 1 fanbeam collimator, compared with a triple-fanbeam collimator, can increase the photon detection efficiency by 27% and by more than a factor of 2, compared with triple-parallel-hole collimation, with equal spatial resolution measured on the axis of rotation. Quantitative analysis of reconstruction bias and visual analysis of the images showed no signs of sampling artifacts. Reconstructed images in the simulations, experimental brain phantom, and patient brain scans showed improved quality with this collimator combination due to increased sensitivity and reduced noise. Lesion visibility was also improved, as confirmed by signal-to-noise ratios. Alternatively, triple-HCB circle-and-helix acquisition has also shown competitive results, with a slight disadvantage in axial sampling and implementation procedure. CONCLUSION: Combined HCB and fanbeam collimation is a promising approach for high-sensitivity brain SPECT.

Characterizing the MTF in 3D for a Quantized SPECT Camera Having Arbitrary Trajectories.

The emergence of application-specific 3D tomographic small animal and dedicated breast imaging systems has stimulated the development of simple methods to quantify the spatial resolution or Modulation Transfer Function (MTF) of the system in three dimensions. Locally determined MTFs, obtained from line source measurements at specific locations, can characterize spatial variations in the system resolution and can help correct for such variations. In this study, a method is described to measure the MTF in 3D for a compact SPECT system that uses a 16 × 20 cm(2) CZT-based compact gamma camera and 3D positioning gantry capable of moving in different trajectories. Image data are acquired for a novel phantom consisting of three radioactivity-filled capillary tubes, positioned nearly orthogonally to each other. These images provide simultaneous measurements of the local MTF along three dimensions of the reconstructed imaged volume. The usefulness of this approach is shown by characterizing the MTF at different locations in the reconstructed imaged 3D volume using various (1) energy windows; (2) iterative reconstruction parameters including number of iterations, voxel size, and number of projection views; (3) simple and complex 3D orbital trajectories including simple vertical axis of rotation, simple tilt, complex circle-plus-arc, and complex sinusoids projected onto a hemisphere; and (4) object shapes in the camera's field of view. Results indicate that the method using the novel phantom can provide information on spatial resolution effects caused by system design, sampling, energy windows, reconstruction parameters, novel 3D orbital trajectories, and object shapes. Based on these measurements that are useful for dedicated tomographic breast imaging, it was shown that there were small variations in the MTF in 3D for various energy windows and reconstruction parameters. However, complex trajectories that uniformly sample the breast volume of interest were quantitatively shown to have slightly better spatial resolution performance than more simple orbits.

Quantitative Evaluation of Half-Cone-Beam Scan Paths in Triple-Camera Brain SPECT.

In this study related to human brain SPECT imaging, simulation of half-cone-beam (HCB) collimation with different scan paths is performed and compared with simulated fan-beam and parallel-hole circular orbit acquisitions of disk-phantom projection data. Acquisition types are quantitatively evaluated based on the photon detection efficiency, the root-mean-squared error, contrast and signal-to-noise ratio measurements of the reconstructed images. We demonstrate that a triple-camera SPECT system with half-cone-beam collimators and circle-and-helix scan paths can offer up to a 26% efficiency increase over fan-beam, and up to a 128% increase over parallel-hole collimators for equal spatial resolutions, and display no visible axial sampling artifacts in reconstructed disk-phantom images. In addition, we perform qualitative experimental evaluation of triple-HCB circle-and-helix acquisition using a Hoffman 3D brain phantom. Reconstructed brain phantom images show improved quality due to reduced noise and no apparent sampling artifacts. Triple-HCB circle-and-helix SPECT has a potential for improved brain imaging, producing higher image quality with a smaller reconstruction error and better lesion detectability due to increased efficiency for equal spatial resolution compared to conventional fan-beam and parallel-hole SPECT.

Brain SPECT Simulation Using Half-Cone-Beam Collimation and Single-Revolution Helical-Path Acquisition.

In this study related to human brain SPECT imaging, simulation of half-cone-beam collimation and helical-path data acquisition is performed. We discuss problems related to circular-orbit acquisition using cone-beam collimation, such as shoulder interference resulting in object truncation, and insufficient sampling of the object resulting in axial distortions in the reconstructed images. We demonstrate that a triple-camera SPECT system with half-cone-beam collimation and single-revolution helical-path acquisition eliminates both issues and offers substantially improved sampling and almost artifact-free reconstruction of the object.

Intertumoral differences in hypoxia selectivity of the PET imaging agent 64Cu(II)-diacetyl-bis(N4-methylthiosemicarbazone).

UNLABELLED: Cu-Diacetyl-bis(N(4)-methylthiosemicarbazone) (Cu-ATSM) is a recently developed PET imaging agent for tumor hypoxia. However, its accuracy and reliability for measuring hypoxia have not been fully characterized in vivo. The aim of this study was to evaluate (64)Cu-ATSM as a hypoxia PET marker by comparing autoradiographic distributions of (64)Cu-ATSM with a well-established hypoxia marker drug, EF5. METHODS: R3230 mammary adenocarcinomas (R3230Ac), fibrosarcomas (FSA), and 9L gliomas (9L) were used in the study. EF5 and Hoechst 33342, a vascular perfusion marker, were administered to the animal for immunohistochemical analysis. (64)Cu-ATSM microPET and autoradiography were performed on the same animal. The tumor-to-muscle ratio (T/M ratio) and standardized uptake values (SUVs) were characterized for these 3 different types of tumors. Five types of images-microPET, autoradiography, EF5 immunostaining, Hoechst fluorescence vascular imaging, and hematoxylin-and-eosin histology-were superimposed, evaluated, and compared. RESULTS: A significantly higher T/M ratio and SUV were seen for FSA compared with R3230Ac and 9L. Spatial correlation analysis between (64)Cu-ATSM autoradiography and EF5 immunostained images varied between the 3 tumor types. There was close correlation of (64)Cu-ATSM uptake and hypoxia in R3230Ac and 9L tumors but not in FSA tumors. Interestingly, elevated (64)Cu-ATSM uptake was observed in well-perfused areas in FSA, indicating a correlation between (64)Cu-ATSM uptake and vascular perfusion as opposed to hypoxia. The same relationship was observed with 2 other hypoxia markers, pimonidazole and carbonic anhydrase IX, in FSA tumors. Breathing carbogen gas significantly decreased the hypoxia level measured by EF5 staining in FSA-bearing rats but not the uptake of (64)Cu-ATSM. These results indicate that some other (64)Cu-ATSM retention mechanisms, as opposed to hypoxia, are involved in this type of tumor. CONCLUSION: To our knowledge, this study is the first comparison between (64)Cu-ATSM uptake and immunohistochemistry in these 3 tumors. Although we have shown that (64)Cu-ATSM is a valid PET hypoxia marker in some tumor types, but not for all, this tumor type-dependent hypoxia selectivity of (64)Cu-ATSM challenges the use of (64)Cu-ATSM as a universal PET hypoxia marker. Further studies are needed to define retention mechanisms for this PET marker.

Analysis of a novel offset cone-beam computed mammotomography system geometry for accomodating various breast sizes.

We evaluate a newly developed dedicated cone-beam transmission computed mammotomography (CmT) system configuration using an optimized quasi-monochromatic cone beam technique for attenuation correction of SPECT in a planned dual-modality emission and transmission system for pendant, uncompressed breasts. In this study, we perform initial CmT acquisitions using various sized breast phantoms to evaluate an offset cone-beam geometry. This offset geometry provides conjugate projections through a full 360 degree gantry rotation, and thus yields a greatly increased effective field of view, allowing a much wider range of breast sizes to be imaged without truncation in reconstructed images. Using a tungsten X-ray tube and digital flat-panel X-ray detector in a compact geometry, we obtained initial CmT scans without shift and with the offset geometry, using geometrical frequency/resolution phantoms and two different sizes of breast phantoms. Acquired data were reconstructed using an ordered subsets transmission iterative algorithm. Projection images indicate that the larger, 20 cm wide, breast requires use of a half-cone-beam offset scan to eliminate truncation artifacts. Reconstructed image results illustrate elimination of truncation artifacts, and that the novel quasi-monochromatic beam yields reduced beam hardening. The offset geometry CmT system can indeed potentially be used for structural imaging and accurate attenuation correction for the functional dedicated breast SPECT system.

Evaluation of fully 3-D emission mammotomography with a compact cadmium zinc telluride detector.

A compact, dedicated cadmium zinc telluride (CZT) gamma camera coupled with a fully three-dimensional (3-D) acquisition system may serve as a secondary diagnostic tool for volumetric molecular imaging of breast cancers, particularly in cases when mammographic findings are inconclusive. The developed emission mammotomography system comprises a medium field-of-view, quantized CZT detector and 3-D positioning gantry. The intrinsic energy resolution, sensitivity and spatial resolution of the detector are evaluated with Tc-99m (140 keV) filled flood sources, capillary line sources, and a 3-D frequency-resolution phantom. To mimic realistic human pendant, uncompressed breast imaging, two different phantom shapes of an average sized breast, and three different lesion diameters are imaged to evaluate the system for 3-D mammotomography. Acquisition orbits not possible with conventional emission, or transmission, systems are designed to optimize the viewable breast volume while improving sampling of the breast and anterior chest wall. Complications in camera positioning about the patient necessitate a compromise in these two orbit design criteria. Image quality is evaluated with signal-to-noise ratios and contrasts of the lesions, both with and without additional torso phantom background. Reconstructed results indicate that 3-D mammotomography, incorporating a compact CZT detector, is a promising, dedicated breast imaging technique for visualization of tumors < 1 cm in diameter. Additionally, there are no outstanding trajectories that consistently yield optimized quantitative lesion imaging parameters. Qualitatively, imaging breasts with realistic torso backgrounds (out-of-field activity) substantially alters image characteristics and breast morphology unless orbits which improve sampling are utilized. In practice, the sampling requirement may be less strict than initially anticipated.

Dosimetry and radiographic analysis of 131I-labeled anti-tenascin 81C6 murine monoclonal antibody in newly diagnosed patients with malignant gliomas: a phase II study.

UNLABELLED: The objective was to perform dosimetry and evaluate dose-response relationships in newly diagnosed patients with malignant brain tumors treated with direct injections of (131)I-labeled anti-tenascin murine 81C6 monoclonal antibody (mAb) into surgically created resection cavities (SCRCs) followed by conventional external-beam radiotherapy and chemotherapy. METHODS: Absorbed doses to the 2-cm-thick shell, measured from the margins of the resection cavity interface, were estimated for 33 patients with primary brain tumors. MRI/SPECT registrations were used to assess the distribution of the radiolabeled mAb in brain parenchyma. Results from biopsies obtained from 15 patients were classified as tumor, radionecrosis, or tumor and radionecrosis, and these were correlated with absorbed dose and dose rate. Also, MRI/PET registrations were used to assess radiographic progression among patients. RESULTS: This therapeutic strategy yielded a median survival of 86 and 79 wk for all patients and glioblastoma multiforme (GBM) patients, respectively. The average SCRC residence time of (131)I-mu81C6 mAb was 76 h (range, 34-169 h). The average absorbed dose to the 2-cm cavity margins was 48 Gy (range, 25-116 Gy) for all patients and 51 Gy (range, 27-116 Gy) for GBM patients. In MRI/SPECT registrations, we observed a preferential distribution of (131)I-mu81C6 mAb through regions of vasogenic edema. An analysis of the relationship between the absorbed dose and dose rate and the first biopsy results yielded a most favorable absorbed dose of 44 Gy. A correlation between decreased survival and irreversible neurotoxicity was noted. A comparative analysis, in terms of median survival, was performed with previous brachytherapy clinical studies, which showed a proportional relationship between the average boost absorbed dose and the median survival. CONCLUSION: This study shows that (131)I-mu81C6 mAb increases the median survival of GBM patients. An optimal absorbed dose of 44 Gy to the 2-cm cavity margins is suggested to reduce the incidence of neurologic toxicity. Further clinical studies are warranted to determine the effectiveness of (131)I-mu81C6 mAb based on a target dose of 44 Gy rather than a fixed administered activity.

Phase 1 trial study of 131I-labeled chimeric 81C6 monoclonal antibody for the treatment of patients with non-Hodgkin lymphoma.

We report a phase 1 study of pharmacokinetics, dosimetry, toxicity, and response of (131)I anti-tenascin chimeric 81C6 for the treatment of lymphoma. Nine patients received a dosimetric dose of 370 MBq (10 mCi). Three patients received an administered activity of 1480 MBq (40 mCi), and 2 developed hematologic toxicity that required stem cell infusion. Six patients received an administered activity of 1110 MBq (30 mCi), and 2 developed toxicity that required stem cell infusion. The clearance of whole-body activity was monoexponential with a mean effective half-life of 110 hours (range, 90-136 hours) and a mean effective whole-body residence time of 159 hours (range, 130-196 hours). There was rapid uptake within the viscera; however, tumor uptake was slower. Activity in normal viscera decreased proportional to the whole body; however, tumor sites presented a slow clearance (T(1/2), 86-191 hours). The mean absorbed dose to whole-body was 67 cGy (range, 51-89 hours), whereas the dose to tumor sites was 963 cGy (range, 363-1517 cGy). Despite lack of a "blocking" antibody, 1 of 9 patients attained a complete remission and 1 a partial remission. These data demonstrate this radiopharmaceutical to be an encouraging agent for the treatment of lymphoma particularly if methods to protect the normal viscera are developed.

Mammotomography with pinhole incomplete circular orbit SPECT.

UNLABELLED: Dedicated mammotomography with pinhole incomplete circular orbit (PICO) SPECT imaging of an uncompressed pendant breast was evaluated with small, very-high-stopping-power pinhole apertures. Comparisons were made with planar pinhole scintimammography. Enhanced 3-dimensional imaging performance with very-high-stopping-power apertures is thought to ultimately yield improved sensitivities for lesion detection and identification in breast disease. METHODS: Pinhole collimators made of high-density and high atomic number (184)W or depleted (238)U, with aperture diameters from 1 to 4 mm, were used to image 0.6- and 1.0-cm-diameter spherical lesions in a pendulous, uncompressed breast phantom in planar and PICO-SPECT modes. The breast was centered on the horizontal axis of rotation of an incomplete circular orbit. Lesion, breast and body, and myocardial activities (L:B:M) were included in the phantoms to simulate clinical imaging conditions with (99m)Tc (140 keV). Lesion contrasts and signal-to-noise ratios (SNRs) for all apertures were determined for near clinical acquisition times for L:B:M ratios of 12:1:20 and 7:1:25. A set of minidisks inserted in the breast phantom was scanned to determine sampling limitations at depth from the nipple. In an initial study, a patient with biopsy-confirmed breast carcinoma was injected with 960 MBq (99m)Tc-tetrofosmin and scanned 2 h later with planar pinhole and PICO-SPECT techniques. RESULTS: Overall, for PICO-SPECT imaging there were small differences in measured counting rate sensitivity (4.9%) and lesion contrast (8.8%) with larger SNR differences (20.8%) between tungsten and depleted uranium pinhole materials at this energy and these lesion sizes. Backgrounds from simulated myocardial uptake had minor contributions in all reconstructed image volumes because of the rapid sensitivity fall-off for pinhole apertures. An optimal aperture diameter between 2 and 3 mm was determined from peak SNR, indicating that these aperture sizes may have the best performance for lesions as small as 0.6 cm in diameter with activity concentration ratios of (99m)Tc similar to those currently seen in patients. Both lesions were visualized with PICO-SPECT better than with planar pinhole imaging, with respective contrast improvements >20 times the values obtained from planar imaging for the same pinholes. In the patient study, higher contrast (>6) visualization of the active tumor periphery was obtained with PICO-SPECT than with planar imaging. CONCLUSION: These results indicate that the enhanced spatial resolution of smaller apertures outweighs the loss in sensitivity in small lesion identification with PICO-SPECT. Although the imaging differences between investigated aperture types are small and some limitations to this imaging approach exist, dedicated PICO-SPECT of the breast appears to be an improved technique compared with conventional planar pinhole scintimammography. This technique provides enhanced contrast and SNR for imaging small lesions with the high-resolution pinhole apertures along with 3-dimensional localization of the lesions.