The Quest for an Accurate Functional Tumor Volume with 68Ga-DOTATATE PET/CT.

68Ga-labeled somatostatin analog (SSA) PET/CT is now a standard-of-care component in the management of neuroendocrine tumors (NETs). However, treatment response for NETs is still assessed with morphologic size measurements from other modalities, which can result in inaccuracy about the disease burden. Functional tumor volume (FTV) acquired from SSA PET/CT has been suggested as a possible metric, but no validated measurement tool to measure FTV exists. We tested the precision of multiple FTV computational approaches compared with morphologic volume measurements to identify a candidate for incorporation into future FTV studies to assess tumor burden more completely and accurately. Methods: The clinical and imaging data of 327 NET patients were collected at Memorial Sloan Kettering Cancer Center between December 2016 and April 2018. Patients were required to have SSA PET/CT and dedicated CT scans within 6 wk and were excluded if they had any intervention between scans. When paired studies were evaluated, 150 correlating lesions demonstrated SSA. Lesions were excluded if they contained necrotic components or were lobulated. This exclusion resulted in 94 lesions in 20 patients. The FTV for each lesion was evaluated with a hand-drawn assessment and 3 automated techniques: 50% threshold from SUVmax, 42% threshold from SUVmax, and background-subtracted lesion activity. These measurements were compared with volume calculated from morphologic volume measurements. Results: The FTV calculation methods showed varying correlations with morphologic volume measurements. FTV using a 42% threshold had a 0.706 correlation, hand-drawn volume from PET imaging had a 0.657 correlation, FTV using a 50% threshold had a 0.645 correlation, and background-subtracted lesion activity had a 0.596 correlation. The Bland-Altman plots indicated that all FTV methods had a positive mean difference from morphologic volume, with a 50% threshold showing the smallest mean difference. Conclusion: FTV determined with thresholding of SUVmax demonstrated the strongest correlation with traditional morphologic lesion volume assessment and the least bias. This method was more accurate than FTV calculated from hand-drawn volume assessments. Threshold-based automated FTV assessment promises to better determine disease extent and prognosis in patients with NETs.

Toward a standard for the evaluation of PET-Auto-Segmentation methods following the recommendations of AAPM task group No. 211: Requirements and implementation.

PURPOSE: The aim of this paper is to define the requirements and describe the design and implementation of a standard benchmark tool for evaluation and validation of PET-auto-segmentation (PET-AS) algorithms. This work follows the recommendations of Task Group 211 (TG211) appointed by the American Association of Physicists in Medicine (AAPM). METHODS: The recommendations published in the AAPM TG211 report were used to derive a set of required features and to guide the design and structure of a benchmarking software tool. These items included the selection of appropriate representative data and reference contours obtained from established approaches and the description of available metrics. The benchmark was designed in a way that it could be extendable by inclusion of bespoke segmentation methods, while maintaining its main purpose of being a standard testing platform for newly developed PET-AS methods. An example of implementation of the proposed framework, named PETASset, was built. In this work, a selection of PET-AS methods representing common approaches to PET image segmentation was evaluated within PETASset for the purpose of testing and demonstrating the capabilities of the software as a benchmark platform. RESULTS: A selection of clinical, physical, and simulated phantom data, including "best estimates" reference contours from macroscopic specimens, simulation template, and CT scans was built into the PETASset application database. Specific metrics such as Dice Similarity Coefficient (DSC), Positive Predictive Value (PPV), and Sensitivity (S), were included to allow the user to compare the results of any given PET-AS algorithm to the reference contours. In addition, a tool to generate structured reports on the evaluation of the performance of PET-AS algorithms against the reference contours was built. The variation of the metric agreement values with the reference contours across the PET-AS methods evaluated for demonstration were between 0.51 and 0.83, 0.44 and 0.86, and 0.61 and 1.00 for DSC, PPV, and the S metric, respectively. Examples of agreement limits were provided to show how the software could be used to evaluate a new algorithm against the existing state-of-the art. CONCLUSIONS: PETASset provides a platform that allows standardizing the evaluation and comparison of different PET-AS methods on a wide range of PET datasets. The developed platform will be available to users willing to evaluate their PET-AS methods and contribute with more evaluation datasets.

Relaxed ordered subset preconditioned alternating projection algorithm for PET reconstruction with automated penalty weight selection.

PURPOSE: Performance of the preconditioned alternating projection algorithm (PAPA) using relaxed ordered subsets (ROS) with a non-smooth penalty function was investigated in positron emission tomography (PET). A higher order total variation (HOTV) regularizer was applied and a method for unsupervised selection of penalty weights based on the measured data is introduced. METHODS: A ROS version of PAPA with HOTV penalty (ROS-HOTV-PAPA) for PET image reconstruction was developed and implemented. Two-dimensional PET data were simulated using two synthetic phantoms (geometric and brain) in geometry similar to GE D690/710 PET/CT with uniform attenuation, and realistic scatter (25%) and randoms (25%). Three count levels (high/medium/low) corresponding to mean information densities (ID¯s) of 125, 25, and 5 noise equivalent counts (NEC) per support voxel were reconstructed using ROS-HOTV-PAPA. The patients' brain and whole body PET data were acquired at similar ID¯s on GE D690 PET/CT with time-of-fight and were reconstructed using ROS-HOTV-PAPA and available clinical ordered-subset expectation-maximization (OSEM) algorithms. A power-law model of the penalty weights' dependence on ID¯ was semi-empirically derived. Its parameters were elucidated from the data and used for unsupervised selection of the penalty weights within a reduced search space. The resulting image quality was evaluated qualitatively, including reduction of staircase artifacts, image noise, spatial resolution and contrast, and quantitatively using root mean squared error (RMSE) as a global metric. The convergence rates were also investigated. RESULTS: ROS-HOTV-PAPA converged rapidly, in comparison to non-ROS-HOTV-PAPA, with no evidence of limit cycle behavior. The reconstructed image quality was superior to optimally post-filtered OSEM reconstruction in terms of noise, spatial resolution, and contrast. Staircase artifacts were not observed. Images of the measured phantom reconstructed using ROS-HOTV-PAPA showed reductions in RMSE of 5%-44% as compared with optimized OSEM. The greatest improvement occurred in the lowest count images. Further, ROS-HOTV-PAPA reconstructions produced images with RMSE similar to images reconstructed using optimally post-filtered OSEM but at one-quarter the NEC. CONCLUSION: Acceleration of HOTV-PAPA was achieved using ROS. This was accompanied by an improved RMSE metric and perceptual image quality that were both superior to that obtained with either clinical or optimized OSEM. This may allow up to a four-fold reduction of the radiation dose to the patients in a PET study, as compared with current clinical practice. The proposed unsupervised parameter selection method provided useful estimates of the penalty weights for the selected phantoms' and patients' PET studies. In sum, the outcomes of this research indicate that ROS-HOTV-PAPA is an appropriate candidate for clinical applications and warrants further research.

PET quantification with a histogram derived total activity metric: superior quantitative consistency compared to total lesion glycolysis with absolute or relative SUV thresholds in phantoms and lung cancer patients.

INTRODUCTION: The increasing use of molecular imaging probes as biomarkers in oncology emphasizes the need for robust and stable methods for quantifying tracer uptake in PET imaging. The primary motivation for this research was to find an accurate method to quantify the total tumor uptake. Therefore we developed a histogram-based method to calculate the background subtracted lesion (BSL) activity and validated BSL by comparing the quantitative consistency with the total lesion glycolysis (TLG) in phantom and patient studies. METHODS: A thorax phantom and a PET-ACR quality assurance phantom were scanned with increasing FDG concentrations. Volumes of interest (VOIs) were placed over each chamber. TLG was calculated with a fixed threshold at SUV 2.5 (TLG2.5) and a relative threshold at 42% of SUVmax (TLG42%). The histogram for each VOI was built and BSL was calculated. Comparison with the total injected FDG activity (TIA) was performed using concordance correlation coefficients (CCC) and the slope (a). Fifty consecutive patients with FDG-avid lung tumors were selected under an IRB waiver. TLG42%, TLG2.5 and BSL were compared to the reference standard calculating CCC and the slope. RESULTS: In both phantoms, the CCC for lesions with a TIA ≤50ml*SUV between TIA and BSL was higher and the slope closer to 1 (CCC=0.933, a=1.189), than for TLG42% (CCC=0.350, a=0.731) or TLG2.5 (CCC=0.761, a=0.727). In 50 lung lesions BSL had a slope closer to 1 compared to the reference activity than TLG42% (a=1.084 vs 0.618 - for high activity lesions) and also closer to 1 than TLG2.5 (a=1.117 vs 0.548 - for low activity lesions). CONCLUSION: The histogram based BSL correlated better with TIA in both phantom studies than TLG2.5 or TLG42%. Also in lung tumors, the BSL activity is overall more accurate in quantifying the lesion activity compared to the two most commonly applied TLG quantification methods.