Supplemental Transmission Aided Attenuation Correction for Quantitative Cardiac PET.

Quantitative PET attenuation correction (AC) for cardiac PET/CT and PET/MR is a challenging problem. We propose and evaluate an AC approach that uses coincidences from a relatively weak and physically fixed sparse external source, in combination with that from the patient, to reconstruct µ -maps based on physics principles alone. The low 30 cm3 volume of the source makes it easy to fill and place, and the method does not use prior image data or attenuation map assumptions. Our supplemental transmission aided maximum likelihood reconstruction of attenuation and activity (sTX-MLAA) algorithm contains an attenuation map update that maximizes the likelihood of terms representing coincidences originating from tracer in the patient and a weighted expression of counts segmented from the external source alone. Both external source and patient scatter and randoms are fully corrected. We evaluated performance of sTX-MLAA compared to reference standard CT-based AC with FDG PET/CT phantom studies; including modeling a patient with myocardial inflammation. Through an ROI analysis we measured ≤ 5 % bias in activity concentrations for PET images generated with sTX-MLAA and a TX source strength ≥ 12.7 MBq, relative to CT-AC. PET background variability (from noise and sparse sampling) was substantially reduced with sTX-MLAA compared to using counts segmented from the transmission source alone for AC. Results suggest that sTX-MLAA will enable quantitative PET during cardiac PET/CT and PET/MR of human patients.

Development of a classifier for [18F]fluorodeoxyglucose extravasation severity using semi-quantitative readings from topically applied detectors.

BACKGROUND: Radiotracer extravasations, caused largely by faulty tracer injections, can occur in up to 23% of 18F-fluorodeoxyglucose (FDG) PET/CT scans and negatively impact radiological review and tracer quantification. Conventional radiological assessment of extravasation severity on PET has limited performance (e.g., extravasations frequently resolve before scanning) and practical drawbacks. In this study, we develop a new topical detector-based FDG extravasation severity classifier, calibrated from semi-quantitative PET measurements, and assess its performance on human subjects. METHODS: A retrospective study examined patients whose FDG injections had been monitored as part of their standard workup for PET/CT imaging. Topical uncollimated gamma ray detectors were applied proximal to the injection site and on the same location on the opposing arm, and readings were acquired continuously during radiotracer uptake. Patients were imaged with their arms in the PET field of view and total extravasation activity quantified from static PET images through a volume of interest approach. The image-derived activities were considered ground truth and used to calibrate and assess quantification of topical detector readings extrapolated to the start of PET imaging. The classifier utilizes the calibrated detector readings to produce four extravasation severity classes: none, minor, moderate, and severe. In a blinded study, a radiologist qualitatively labeled PET images for extravasation severity using the same classifications. The radiologist's interpretations and topical detector classifications were compared to the ground truth PET results. RESULTS: Linear regression of log-transformed image-derived versus topical detector tracer extravasation activity estimates showed a strong correlation (R2 = 0.75). A total of 24 subject scans were cross-validated with the quantitatively based classifier through a leave-one-out methodology. For binary classification (none vs. extravasated), the topical detector classifier had the highest overall diagnostic performance for identifying extravasations. Specificity, sensitivity, accuracy, and positive predictive value were 100.0%, 80.0%, 95.8%, and 100.0%, respectively, for the topical detector classifier and 31.6%, 100.0%, 45.8%, and 27.8%, respectively, for the radiological analysis. The topical detector classifier, with an optimal detection threshold, produced a significantly higher Matthews correlation coefficient (MCC) than the radiological analysis (0.87 vs. 0.30). CONCLUSIONS: The topical detector binary classifier, calibrated using quantitative static PET measurements, significantly improves extravasation detection compared to qualitative image analysis.

Comparison of maximum likelihood and conventional PET scatter scaling methods for 18 F-FDG and 68 Ga-DOTATATE PET/CT.

PURPOSE: We aim to quantify differences between a new maximum likelihood (ML) background scaling (MLBS) algorithm and two conventional scatter scaling methods for clinical PET/CT. A common source of reduced image quantification with conventional scatter corrections is attributed to erroneous scaling of the initial scatter estimate to match acquired scattered events in the sinogram. MLBS may have performance advantages over conventional methods by using all available data intersecting the subject. METHODS: A retrospective analysis was performed on subjects injected with 18 F-FDG (N = 71) and 68 Ga-DOTATATE (N = 11) and imaged using time-of-flight (TOF) PET/CT. The scatter distribution was estimated with single scatter simulation approaches. Conventional scaling algorithms included (a) tail fitted background scaling (TFBS), which scales the scatter to "tails" outside the emission support, and (b) absolute scatter correction (ABS), which utilizes the simulated scatter distribution with no scaling applied. MLBS consisted of an alternating iterative reconstruction with a TOF-based ML activity image update allowing negative values (NEG-ML) and nested loop ML scatter scaling estimation. Scatter corrections were compared using reconstructed images as follows: (a) normalized relative difference images were generated and used for voxel-wise analysis, (b) liver and suspected lesion ROIs were drawn to compute mean SUVs, and (c) a qualitative analysis of overall diagnostic image quality, impact of artifacts, and lesion conspicuity was performed. Absolute quantification and normalized relative differences were also assessed with an 18 F-FDG phantom study. RESULTS: For human subjects 18 F-FDG data, Bland-Altman plots demonstrated that the largest normalized voxel-wise differences were observed close to the lower limit (SUV = 1.0). MLBS reconstructions trended towards higher scatter fractions compared to TFBS and ABS images, with median voxel differences across all subjects for TFBS-MLBS measured at 1.7% and 7.6% for 18 F-FDG and 68 Ga-DOTATATE, respectively. For mean SUV analysis, there was a high degree of correlation between the scatter corrections. For 18 F-FDG, ABS scatter correction reconstructions trended towards higher liver mean SUVs relative to MLBS. The qualitative image analysis revealed no significant differences between TFBS and MLBS image reconstructions. For a uniformly filled relatively large 37 cm diameter phantom, MLBS produced the lowest bias in absolute quantification, while normalized voxel-wise differences showed a trend in scatter correction performance consistent with the human subjects study. CONCLUSIONS: For 18 F-FDG, MLBS is at least a valid substitute to TFBS, providing reconstructed image performance comparable to TFBS in most subjects but exhibiting quantitative differences in cases where TFBS is typically prone to inaccuracies (e.g., due to patient motion and CT-based attenuation map truncation). Particularly for low contrast regions, quantification differs for ABS compared to MLBS and TFBS, and caution should be taken when utilizing ABS for decision-making based on quantitative metrics.

Transmission imaging for integrated PET-MR systems.

Attenuation correction for PET-MR systems continues to be a challenging problem, particularly for body regions outside the head. The simultaneous acquisition of transmission scan based µ-maps and MR images on integrated PET-MR systems may significantly increase the performance of and offer validation for new MR-based µ-map algorithms. For the Biograph mMR (Siemens Healthcare), however, use of conventional transmission schemes is not practical as the patient table and relatively small diameter scanner bore significantly restrict radioactive source motion and limit source placement. We propose a method for emission-free coincidence transmission imaging on the Biograph mMR. The intended application is not for routine subject imaging, but rather to improve and validate MR-based µ-map algorithms; particularly for patient implant and scanner hardware attenuation correction. In this study we optimized source geometry and assessed the method's performance with Monte Carlo simulations and phantom scans. We utilized a Bayesian reconstruction algorithm, which directly generates µ-map estimates from multiple bed positions, combined with a robust scatter correction method. For simulations with a pelvis phantom a single torus produced peak noise equivalent count rates (34.8 kcps) dramatically larger than a full axial length ring (11.32 kcps) and conventional rotating source configurations. Bias in reconstructed µ-maps for head and pelvis simulations was ⩽4% for soft tissue and ⩽11% for bone ROIs. An implementation of the single torus source was filled with (18)F-fluorodeoxyglucose and the proposed method quantified for several test cases alone or in comparison with CT-derived µ-maps. A volume average of 0.095 cm(-1) was recorded for an experimental uniform cylinder phantom scan, while a bias of <2% was measured for the cortical bone equivalent insert of the multi-compartment phantom. Single torus µ-maps of a hip implant phantom showed significantly less artifacts and improved dynamic range, and differed greatly for highly attenuating materials in the case of the patient table, compared to CT results. Use of a fixed torus geometry, in combination with translation of the patient table to perform complete tomographic sampling, generated highly quantitative measured µ-maps and is expected to produce images with significantly higher SNR than competing fixed geometries at matched total acquisition time.

Different partial volume correction methods lead to different conclusions: An (18)F-FDG-PET study of aging.

A cross-sectional group study of the effects of aging on brain metabolism as measured with (18)F-FDG-PET was performed using several different partial volume correction (PVC) methods: no correction (NoPVC), Meltzer (MZ), Müller-Gärtner (MG), and the symmetric geometric transfer matrix (SGTM) using 99 subjects aged 65-87years from the Harvard Aging Brain study. Sensitivity to parameter selection was tested for MZ and MG. The various methods and parameter settings resulted in an extremely wide range of conclusions as to the effects of age on metabolism, from almost no changes to virtually all of cortical regions showing a decrease with age. Simulations showed that NoPVC had significant bias that made the age effect on metabolism appear to be much larger and more significant than it is. MZ was found to be the same as NoPVC for liberal brain masks; for conservative brain masks, MZ showed few areas correlated with age. MG and SGTM were found to be similar; however, MG was sensitive to a thresholding parameter that can result in data loss. CSF uptake was surprisingly high at about 15% of that in gray matter. The exclusion of CSF from SGTM and MG models, which is almost universally done, caused a substantial loss in the power to detect age-related changes. This diversity of results reflects the literature on the metabolism of aging and suggests that extreme care should be taken when applying PVC or interpreting results that have been corrected for partial volume effects. Using the SGTM, significant age-related changes of about 7% per decade were found in frontal and cingulate cortices as well as primary visual and insular cortices.

Effects of ferumoxytol on quantitative PET measurements in simultaneous PET/MR whole-body imaging: a pilot study in a baboon model.

BACKGROUND: Simultaneous PET/MR imaging depends on MR-derived attenuation maps (mu-maps) for accurate attenuation correction of PET data. Currently, these maps are derived from gradient-echo-based MR sequences, which are sensitive to susceptibility changes. Iron oxide magnetic nanoparticles have been used in the measurement of blood volume, tumor microvasculature, tumor-associated macrophages, and characterizing lymph nodes. Our aim in this study was to assess whether the susceptibility effects associated with iron oxide nanoparticles can potentially affect measured (18)F-FDG PET standardized uptake values (SUV) through effects on MR-derived attenuation maps. METHODS: The study protocol was approved by the Institutional Animal Care and Use Committee. Using a Siemens Biograph mMR PET/MR scanner, we evaluated the effects of increasing concentrations of ferumoxytol and ferumoxytol aggregates on MR-derived mu-maps using an agarose phantom. In addition, we performed a baboon experiment evaluating the effects of a single i.v. ferumoxytol dose (10 mg/kg) on the liver, spleen, and pancreas (18)F-FDG SUV at baseline (ferumoxytol-naïve), within the first hour and at 1, 3, 5, and 11 weeks. RESULTS: Phantom experiments showed mu-map artifacts starting at ferumoxytol aggregate concentrations of 10 to 20 mg/kg. The in vivo baboon data demonstrated a 53% decrease of observed (18)F-FDG SUV compared to baseline within the first hour in the liver, persisting at least 11 weeks. CONCLUSIONS: A single ferumoxytol dose can affect measured SUV for at least 3 months, which should be taken into account when administrating ferumoxytol in patients needing sequential PET/MR scans. Advances in knowledge 1. Ferumoxytol aggregates, but not ferumoxytol alone, produce significant artifacts in MR-derived attenuation correction maps at approximate clinical dose levels of 10 mg/kg. 2. When performing simultaneous whole-body (18)F-FDG PET/MR, a single dose of ferumoxytol can result in observed SUV decreases up to 53%, depending on the amount of ferumoxytol aggregates in the studied tissue. Implications for patient care Administration of a single, clinically relevant, dose of ferumoxytol can potentially result in changes in observed SUV for a prolonged period of time in the setting of simultaneous PET/MR. These potential changes should be considered in particular when administering ferumoxytol to patients with expected future PET/MR studies, as ferumoxytol-induced SUV changes might interfere with therapy assessment.

Influence of the partial volume correction method on (18)F-fluorodeoxyglucose brain kinetic modelling from dynamic PET images reconstructed with resolution model based OSEM.

Kinetic parameters estimated from dynamic (18)F-fluorodeoxyglucose ((18)F-FDG) PET acquisitions have been used frequently to assess brain function in humans. Neglecting partial volume correction (PVC) for a dynamic series has been shown to produce significant bias in model estimates. Accurate PVC requires a space-variant model describing the reconstructed image spatial point spread function (PSF) that accounts for resolution limitations, including non-uniformities across the field of view due to the parallax effect. For ordered subsets expectation maximization (OSEM), image resolution convergence is local and influenced significantly by the number of iterations, the count density, and background-to-target ratio. As both count density and background-to-target values for a brain structure can change during a dynamic scan, the local image resolution may also concurrently vary. When PVC is applied post-reconstruction the kinetic parameter estimates may be biased when neglecting the frame-dependent resolution. We explored the influence of the PVC method and implementation on kinetic parameters estimated by fitting (18)F-FDG dynamic data acquired on a dedicated brain PET scanner and reconstructed with and without PSF modelling in the OSEM algorithm. The performance of several PVC algorithms was quantified with a phantom experiment, an anthropomorphic Monte Carlo simulation, and a patient scan. Using the last frame reconstructed image only for regional spread function (RSF) generation, as opposed to computing RSFs for each frame independently, and applying perturbation geometric transfer matrix PVC with PSF based OSEM produced the lowest magnitude bias kinetic parameter estimates in most instances, although at the cost of increased noise compared to the PVC methods utilizing conventional OSEM. Use of the last frame RSFs for PVC with no PSF modelling in the OSEM algorithm produced the lowest bias in cerebral metabolic rate of glucose estimates, although by less than 5% in most cases compared to the other PVC methods. The results indicate that the PVC implementation and choice of PSF modelling in the reconstruction can significantly impact model parameters.

Quantification with a dedicated breast PET/CT scanner.

PURPOSE: Dedicated breast PET/CT is expected to have utility in local staging, surgical planning, monitoring of therapy response, and detection of residual disease for breast cancer. Quantitative metrics will be integral to several such applications. The authors present a validation of fully 3D data correction schemes for a custom built dedicated breast PET/CT (DbPET/CT) scanner via (18)F-FDG phantom scans. METHODS: A component-based normalization was implemented, live-time was estimated with a multicomponent model, and a variance reduced randoms estimate was computed from delayed coincidences. Attenuation factors were calculated by using a CT based segmentation scheme while scatter was computed using a Monte Carlo (MC) simulation method. As no performance standard currently exists for breast PET systems, custom performance tests were created based on prior patient imaging results. Count-rate linearity for live-time and randoms corrections was measured with a decay experiment for a solid polyethylene cylinder phantom with an offset line source. A MC simulation was used to validate attenuation correction, a multicompartment phantom with asymmetric activity distribution provided an assessment of scatter correction, and image uniformity after geometric and detector normalization was measured from a high count scan of a uniform cylinder phantom. Raw data were reconstructed with filtered back projection (FBP) after Fourier rebinning. To quantify performance absolute activity concentrations, contrast recovery coefficients and image uniformity were calculated through region of interest analysis. RESULTS: The most significant source of error was attributed to mispositioning of events due to pile-up, presenting in count-related axial and transaxial nonuniformities that were not corrected for with the normalization method used here. Within the range of singles counts observed during clinical trials residual error after applying all corrections was comparable to that of a commercial whole body PET/CT system. CONCLUSIONS: The results suggest that DbPET/CT is capable of producing quantitative images under the operating conditions expected during patient imaging.

Simulation study of spatial resolution and sensitivity for the tapered depth of interaction PET detectors for small animal imaging.

Improvements to current small animal PET scanners can be made by improving the sensitivity and the spatial resolution of the scanner. In the past, efforts have been made to minimize the crystal dimensions in the axial and transaxial directions to improve the spatial resolution and to increase the crystal length to improve the sensitivity of the scanner. We have designed tapered PET detectors with the purpose of reducing the gaps between detector modules and optimizing the sensitivity of a future-generation small animal PET scanner. In this work, we investigate spatial resolution and sensitivity of a scanner based on tapered detector elements using Monte Carlo simulations. For tapered detector elements more scintillation material is used per detector resulting in a higher sensitivity of the scanner. However, since the detector elements are not uniform in size, degradation in spatial resolution is also expected. To investigate characteristics of tapered PET detectors, the spatial resolution and sensitivity of a one-ring scanner were simulated for a system based on traditional cuboid detectors and a scanner based on tapered detectors. Additionally, the effect of depth of interaction (DOI) resolution on the spatial resolution for the traditional and tapered detectors was evaluated. All simulations were performed using the Monte Carlo simulation package GATE. Using the tapered arrays, a 64% improvement in the sensitivity across the field of view was found compared with traditional detectors for the same ring diameter. The level of DOI encoding was found to be the dominating factor in determining the radial spatial resolution and not the detector shape. For all levels of DOI encoding, no significant difference was found for the spatial resolution when comparing the tapered and the cuboid detectors. Detectors employing the tapered crystal design along with excellent DOI resolution will lead to PET scanners with higher sensitivity and uniform spatial resolution across the field of view.

Initial characterization of a dedicated breast PET/CT scanner during human imaging.

UNLABELLED: We have constructed a dedicated breast PET/CT scanner capable of high-resolution functional and anatomic imaging. Here, we present an initial characterization of scanner performance during patient imaging. METHODS: The system consisted of a lutetium oxyorthosilicate-based dual-planar head PET camera (crystal size, 3 x 3 x 20 mm) and 768-slice cone-beam CT. The position of the PET heads (separation and height) could be adjusted for varying breast dimensions. For scanning, the patient lay prone on a specialized bed and inserted a single pendent breast through an aperture in the table top. Compression of the breast as used in mammography is not required. PET and CT systems rotate in the coronal plane underneath the patient sequentially to collect fully tomographic datasets. PET images were reconstructed with the fully 3-dimensional maximum a posteriori method, and CT images were reconstructed with the Feldkamp algorithm, then spatially registered and fused for display. Phantom scans were obtained to assess the registration accuracy between PET and CT images and the influence of PET electronics and activity on CT image quality. We imaged 4 women with mammographic findings highly suggestive of breast cancer (breast imaging reporting and data system, category 5) in an ongoing clinical trial. Patients were injected with (18)F-FDG and imaged for 12.5 min per breast. From patient data, noise-equivalent counting rates and the singles-to-trues ratio (a surrogate for the randoms fraction) were calculated. RESULTS: The average registration error between PET and CT images was 0.18 mm. PET electronics and activity did not significantly affect CT image quality. For the patient trial, biopsy-confirmed cancers were visualized on dedicated breast PET/CT on all patient scans, including the detection of ductal carcinoma in situ in 1 case. The singles-to-trues ratio was found to be inversely correlated with breast volume in the field of view, suggesting that larger breasts trend toward increased noise-equivalent counting rates for all other things equal. CONCLUSION: Scanning of the uncompressed breast with dedicated breast PET/CT can accurately visualize suspected lesions in 3 dimensions.

PET characteristics of a dedicated breast PET/CT scanner prototype.

A dedicated breast PET/CT system has been constructed at our institution, with the goal of having increased spatial resolution and sensitivity compared to whole-body systems. The purpose of this work is to describe the design and the performance characteristics of the PET component of this device. Average spatial resolution of a line source in warm background using maximum a posteriori (MAP) reconstruction was 2.5 mm, while the average spatial resolution of a phantom containing point sources using filtered back projection (FBP) was 3.27 mm. A sensitivity profile was computed with a point source translated across the axial field of view (FOV) and a peak sensitivity of 1.64% was measured at the center of the FOV. The average energy resolution determined on a per-crystal basis was 25%. The characteristic dead time for the front-end electronics and data acquisition (DAQ) was determined to be 145 ns and 3.6 micros, respectively. With no activity outside the FOV, a peak noise-equivalent count rate of 18.6 kcps was achieved at 318 microCi (11.766 MBq) in a cylindrical phantom of diameter 75 mm. After the effects of exposing PET detectors to x-ray flux were evaluated and ameliorated, a combined PET/CT scan was performed. The percentage standard deviations of uniformity along axial and transaxial directions were 3.7% and 2.8%, respectively. The impact of the increased reconstructed spatial resolution compared to typical whole-body PET scanners is currently being assessed in a clinical trial.

Crystal identification in positron emission tomography using nonrigid registration to a Fourier-based template.

Modern positron emission tomography (PET) detectors are typically made from 2D modular arrays of scintillation crystals. Their characteristic flood field response (or flood histogram) must be segmented in order to correctly determine the crystal of annihilation photon interaction in the system. Crystal identification information thus generated is also needed for accurate system modeling as well as for detailed detector characterization and performance studies. In this paper, we present a semi-automatic general purpose template-guided scheme for the segmentation of flood histograms. We first generate a template image that exploits the spatial frequency information in the given flood histogram using Fourier-space analysis. This template image is a lower order approximation of the flood histogram, and can be segmented with horizontal and vertical lines drawn midway between adjacent peaks in the histogram. The template is then registered to the given flood histogram by a diffeomorphic polynomial-based warping scheme that is capable of iteratively minimizing intensity differences. The displacement field thus calculated is applied to the segmentation of the template resulting in a segmentation of the given flood histogram. We evaluate our segmentation scheme for a photomultiplier tube based PET detector, a detector with readout by a position-sensitive avalanche photodiode (PSAPD) and a detector consisting of a stack of photomultiplier tubes and scintillator arrays. Further, we quantitatively compare the performance of the proposed method to that of a manual segmentation scheme using reconstructed images of a line-source phantom. We also present an adaptive method for distortion reduction in flood histograms obtained for PET detectors that use PSAPDs.