Phantom and methodology for comparison of small lesion detectability in PET.

PURPOSE: The main goal of this work is to describe a phantom design, data acquisition and data analysis methodology enabling comparison of small lesion detectability between PET imaging systems and reconstruction algorithms. Several methods are currently available to characterize intrinsic and image quality performance, but none focus exclusively on small lesion detectability. METHODS: We previously developed a small-lesion detection phantom and described initial results using a head-size phantom. Unlike most fillable nuclear medicine phantoms, this phantom offers a semi-realistic heterogenous background and wall-less contrast features. In this work, the methodology is extended to include (a) the use of both head- and body-sized phantoms and (b) a multi-scan data collection and analysis method. We present an example use case of the phantom and detection estimation methodology, comparing the small-lesion detection performance across four commercial PET/CT systems. RESULTS: Repeat acquisitions of the phantom enabled estimation of model observer performance and surrogates of detectability. As anticipated, estimated detectability increased with the square root of system sensitivity and TOF offered marked improvement in detectability, especially for the body sized object. The proposed approach characterizing detectability at different times during the decay of the phantom enabled comparison of small lesion detectability at matched activity concentrations (and scan durations) across different scanners. CONCLUSION: The proposed approach offers a reproducible tool for evaluating relative tradeoffs of system performance on small lesion detectability.

Multi-Objective Evolutionary Algorithm for PET Image Reconstruction: Concept.

In many diagnostic imaging settings, including positron emission tomography (PET), images are typically used for multiple tasks such as detecting disease and quantifying disease. Unlike conventional image reconstruction that optimizes a single objective, this work proposes a multi-objective optimization algorithm for PET image reconstruction to identify a set of images that are optimal for more than one task. This work is reliant on a genetic algorithm to evolve a set of solutions that satisfies two distinct objectives. In this paper, we defined the objectives as the commonly used Poisson log-likelihood function, typically reflective of quantitative accuracy, and a variant of the generalized scan-statistic model, to reflect detection performance. The genetic algorithm uses new mutation and crossover operations at each iteration. After each iteration, the child population is selected with non-dominated sorting to identify the set of solutions along the dominant front or fronts. After multiple iterations, these fronts approach a single non-dominated optimal front, defined as the set of PET images for which none the objective function values can be improved without reducing the opposing objective function. This method was applied to simulated 2D PET data of the heart and liver with hot features. We compared this approach to conventional, single-objective approaches for trading off performance: maximum likelihood estimation with increasing explicit regularization and maximum a posteriori estimation with varying penalty strength. Results demonstrate that the proposed method generates solutions with comparable to improved objective function values compared to the conventional approaches for trading off performance amongst different tasks. In addition, this approach identifies a diverse set of solutions in the multi-objective function space which can be challenging to estimate with single-objective formulations.

Patient factors and outcomes associated with discordance between quantitative and qualitative cardiac PET ischemia information.

BACKGROUND: Cardiac PET can provide quantitative myocardial blood flow (MBF) estimates. The frequency and clinical significance of discordant ischemia information between quantitative and qualitative parameters is unclear. METHODS: This retrospective, cohort study analyzed 256 Rb-82 stress-rest PET/CT studies. Global MBF and myocardial flow reserve (MFR) were estimated in absolute units for quantitative results and sum-stress and difference scores were used for qualitative results. Four groups of patients were evaluated based on a specific definition of concordant and discordant quantitative and qualitative results. RESULTS: 31% of cases demonstrated discordance. Factors associated with microvascular disease were more common in the groups with abnormal quantitative results, regardless of the qualitative findings. Patients with concordant abnormal results had a significantly increased risk of myocardial infarction, heart failure, percutaneous intervention, and all-cause-mortality at 1 year compared to patients with concordant normal results. In patients with discordant results of abnormal quantitative and normal qualitative findings, there was a higher prevalence of heart failure than in controls (12.5% vs 0%, p = 0.01). CONCLUSIONS: Discordance in qualitative and quantitative ischemia measures from PET is common, and further study is needed to clarify its prognostic implications. Moreover, quantitative estimation of MBF and MFR appears to add value to qualitative visual interpretation by supporting qualitative findings when results are concordant. Abnormal quantitative findings, regardless of concordance or discordance with qualitative findings, occurred in patients with risk factors associated with diffuse disease and with increased risk of heart failure admission.

Use of Dual-Energy CT for Quantification of Essential Trace Metals (Iron, Copper, and Zinc): Proof of Concept.

OBJECTIVE. Altered concentrations of essential trace metals have been associated with the development of abdominal tumors. We developed a method to quantify trace metals (iron, copper, and zinc) using monochromatic data from commercially available dual-energy CT (DECT) implementations. CONCLUSION. Our data provide a foundation for the use of DECT for noninvasive quantification of essential trace metals. Minimum detectable concentrations of iron and zinc estimated with DECT overlap with in vivo hepatic concentrations reported in the literature.

Sharing and Selling Images: Ethical and Regulatory Considerations for Radiologists.

Opportunities to share or sell images are common in radiology. But because these images typically originate as protected health information, their use admits a host of ethical and regulatory considerations. This article discusses four scenarios that reflect data sharing or selling arrangements in radiology, especially as they might occur in "big data" systems or applications. The objective of this article is to acquaint radiologists with a variety of regulatory standards and ethical perspectives that pertain to certain data use agreements, such that the attitudes and practices of data holders and their sharers or purchasers can withstand ethical or regulatory scrutiny and not invite undesirable outcomes.

Correction to: Ovarian torsion: developing a machine-learned algorithm for diagnosis.

The original version of this paper included errors in Fig. 3. The corrected Fig. 3 is presented here.

Ovarian torsion: developing a machine-learned algorithm for diagnosis.

BACKGROUND: Ovarian torsion is a common concern in girls presenting to emergency care with pelvic or abdominal pain. The diagnosis is challenging to make accurately and quickly, relying on a combination of physical exam, history and radiologic evaluation. Failure to establish the diagnosis in a timely fashion can result in irreversible ovarian ischemia with implications for future fertility. Ultrasound is the mainstay of evaluation for ovarian torsion in the pediatric population. However, even with a high index of suspicion, imaging features are not pathognomonic. OBJECTIVE: We sought to develop an algorithm to aid radiologists in diagnosing ovarian torsion using machine learning from sonographic features and to evaluate the frequency of each sonographic element. MATERIALS AND METHODS: All pediatric patients treated for ovarian torsion at a quaternary pediatric hospital over an 11-year period were identified by both an internal radiology database and hospital-based International Statistical Classification of Diseases and Related Health Problems (ICD) code review. Inclusion criteria were surgical confirmation of ovarian torsion and available imaging. Patients were excluded if the diagnosis could not be confirmed, no imaging was available for review, the ovary was not identified by imaging, or torsion involved other adnexal structures but spared the ovary. Data collection included: patient age; laterality of torsion; bilateral ovarian volumes; torsed ovarian position, i.e. whether medialized with respect to the mid-uterine line; presence or absence of Doppler signal within the torsed ovary; visualization of peripheral follicles; and presence of a mass or cyst, and free peritoneal fluid. Subsequently, we evaluated a non-torsed control cohort from April 2015 to May 2016. This cohort consisted of sequential girls and young adults presenting to the emergency department with abdominopelvic symptoms concerning for ovarian torsion but who were ultimately diagnosed otherwise. These features were then fed into supervised machine learning systems to identify and develop viable decision algorithms. We divided data into training and validation sets and assessed algorithm performance using sub-sets of the validation set. RESULTS: We identified 119 torsion-confirmed cases and 331 torsion-absent cases. Of the torsion-confirmed cases, significant imaging differences were evident for girls younger than 1 year; these girls were then excluded from analysis, and 99 pediatric patients older than 1 year were included in our study. Among these 99, all variables demonstrated statistically significant differences between the torsion-confirmed and torsion-absent groups with P-values <0.005. Using any single variable to identify torsion provided only modest detection performance, with areas under the curve (AUC) for medialization, peripheral follicles, and absence of Doppler flow of 0.76±0.16, 0.66±0.14 and 0.82±0.14, respectively. The best decision tree using a combination of variables yielded an AUC of 0.96±0.07 and required knowledge of the presence of intra-ovarian flow, peripheral follicles, the volume of both ovaries, and the presence of cysts or masses. CONCLUSION: Based on the largest series of pediatric ovarian torsion in the literature to date, we quantified sonographic features and used machine learning to create an algorithm to identify the presence of ovarian torsion - an algorithm that performs better than simple approaches relying on single features. Although complex combinations using multiple-interaction models provide slightly better performance, a clinically pragmatic decision tree can be employed to detect torsion, providing sensitivity levels of 95±14% and specificity of 92±2%.

Technical Note: A digital reference object representing Hoffman's 3D brain phantom for PET scanner simulations.

PURPOSE: Physical and digital phantoms play a key role in the development and testing of nuclear medicine instrumentation and processing algorithms for clinical and research applications, including neuroimaging using positron emission tomography (PET). We have developed and tested a digital reference object (DRO) version of the original segmented magnetic resonance imaging (MRI) data used for the three-dimensional (3D) PET brain phantom developed by Hoffman et al., which is used as the basis of a commercially available physical test phantom. METHODS: The DRO was constructed by subdividing the MRI image planes the original phantom was based on to create equal-thickness slices and re-labeling voxels. The digital data was then embedded in a PET Digital Imaging and Communications in Medicine format and tested for compliance. RESULTS: We then tested the DRO by comparing it to computed tomography (CT) images of the physical phantom summed to form composite slices with axial extent similar to the DRO, but with a factor of two better in-slice resolution. For composite slices, 91% of voxels were labeled in full agreement, 5% of the voxels were 50-75% accurate, and the remaining 4% of voxels had 25% or less agreement. CONCLUSIONS: This DRO can be used as an input for PET scanner simulation studies or for comparing simulations to measured Hoffman phantom images.

PET/CT-guided biopsy with respiratory motion correction.

PURPOSE: Given the ability of positron emission tomography (PET) imaging to localize malignancies in heterogeneous tumors and tumors that lack an X-ray computed tomography (CT) correlate, combined PET/CT-guided biopsy may improve the diagnostic yield of biopsies. However, PET and CT images are naturally susceptible to problems due to respiratory motion, leading to imprecise tumor localization and shape distortion. To facilitate PET/CT-guided needle biopsy, we developed and investigated the feasibility of a workflow that allows to bring PET image guidance into interventional CT suite while accounting for respiratory motion. METHODS: The performance of PET/CT respiratory motion correction using registered and summed phases method was evaluated through computer simulations using the mathematical 4D extended cardiac-torso phantom, with motion simulated from real respiratory traces. The performance of PET/CT-guided biopsy procedure was evaluated through operation on a physical anthropomorphic phantom. Vials containing radiolabeled 18F-fluorodeoxyglucose were placed within the physical phantom thorax as biopsy targets. We measured the average distance between target center and the simulated biopsy location among multiple trials to evaluate the biopsy localization accuracy. RESULTS: The computer simulation results showed that the RASP method generated PET images with a significantly reduced noise of 0.10 ± 0.01 standardized uptake value (SUV) as compared to an end-of-expiration image noise of 0.34 ± 0.04 SUV. The respiratory motion increased the apparent liver lesion size from 5.4 ± 1.1 to 35.3 ± 3.0 cc. The RASP algorithm reduced this to 15.7 ± 3.7 cc. The distances between the centroids for the static image lesion and two moving lesions in the liver and lung, when reconstructed with the RASP algorithm, were 0.83 ± 0.72 mm and 0.42 ± 0.72 mm. For the ungated imaging, these values increased to 3.48 ± 1.45 mm and 2.5 ± 0.12 mm, respectively. For the ungated imaging, this increased to 1.99 ± 1.72 mm. In addition, the lesion activity estimation (e.g., SUV) was accurate and constant for images reconstructed using the RASP algorithm, whereas large activity bias and variations (± 50%) were observed for lesions in the ungated images. The physical phantom studies demonstrated a biopsy needle localization error of 2.9 ± 0.9 mm from CT. Combined with the localization errors due to respiration for the PET images from simulations, the overall estimated lesion localization error would be 3.08 mm for PET-guided biopsies images using RASP and 3.64 mm when using ungated PET images. In other words, RASP reduced the localization error by approximately 0.6 mm. The combined error analysis showed that replacing the standard end-of-expiration images with the proposed RASP method in PET/CT-guided biopsy workflow yields comparable lesion localization accuracy and reduced image noise. CONCLUSION: The RASP method can produce PET images with reduced noise, attenuation artifacts and respiratory motion, resulting in more accurate lesion localization. Testing the PET/CT-guided biopsy workflow using computer simulation and physical phantoms with respiratory motion, we demonstrated that guided biopsy procedure with the RASP method can benefit from improved PET image quality due to noise reduction, without compromising the accuracy of lesion localization.

Accuracy of Myocardial Blood Flow Estimation From Dynamic Contrast-Enhanced Cardiac CT Compared With PET.

Background The accuracy of absolute myocardial blood flow (MBF) from dynamic contrast-enhanced cardiac computed tomography acquisitions has not been fully characterized. We evaluate computed tomography (CT) compared with rubidium-82 positron emission tomography (PET) MBF estimates in a high-risk population. Methods In a prospective trial, patients receiving clinically indicated rubidium-82 PET exams were recruited to receive a dynamic contrast-enhanced cardiac computed tomography exam. The CT protocol included a rest and stress dynamic portion each acquiring 12 to 18 cardiac-gated frames. The global MBF was estimated from the PET and CT exam. Results Thirty-four patients referred for cardiac rest-stress PET were recruited. Of the 68 dynamic contrast-enhanced cardiac computed tomography scans, 5 were excluded because of injection errors or mismatched hemodynamics. The CT-derived global MBF was highly correlated with the PET MBF (r=0.92; P<0.001) with a mean difference of 0.7±26.4%. The CT MBF estimates were within 20% of PET estimates ( P<0.02) with a mean of (1) MBF for resting flow of PET versus CT of 0.9±0.3 versus 1.0±0.2 mL/min per gram and (2) MBF for stress flow of 2.1±0.7 versus 2.0±0.8 mL/min per gram. Myocardial flow reserve was -14±28% underestimated with CT (PET versus CT myocardial flow reserve, 2.5±0.6 versus 2.2±0.6). The proposed rest+stress+computed tomography angiography protocol had a dose length product of 598±76 mGy×cm resulting in an approximate effective dose of 8.4±1.1 mSv. Conclusions In a high-risk clinical population, a clinically practical dynamic contrast-enhanced cardiac computed tomography provided unbiased MBF estimates within 20% of rubidium-82 PET. Although unbiased, the CT estimates contain substantial variance with an standard error of the estimate of 0.44 mL/min per gram. Myocardial flow reserve estimation was not as accurate as individual MBF estimates.

Performance evaluation of the 5-Ring GE Discovery MI PET/CT system using the national electrical manufacturers association NU 2-2012 Standard.

The GE Discovery MI PET/CT system has a modular digital detector design allowing three, four, or five detector block rings that extend the axial field-of-view (FOV) from 15 to 25 cm in 5 cm increments. This study investigated the performance of the 5-ring system and compared it to 3- and 4-ring systems; the GE Discovery IQ system that uses conventional photomultiplier tubes; and the GE Signa PET/MR system that has a reduced transaxial FOV. METHODS: PET performance was evaluated at three different institutions. Spatial resolution, sensitivity, counting rate performance, accuracy, and image quality were measured in accordance with National Electrical Manufacturers Association NU 2-2012 standards. The mean energy resolution, mean timing resolution, and PET/CT subsystem alignment were also measured. Phantoms were used to determine the effects of varying acquisition time and reconstruction parameters on image quality. Retrospective patient scans were reconstructed with various scan durations to evaluate the impact on image quality. RESULTS: Results from all three institutions were similar. Radial/tangential/axial full width at half maximum spatial resolution measurements using the filtered back projection algorithm were 4.3/4.3/5.0 mm, 5.5/4.6/6.5 mm, and 7.4/5.0/6.6 mm at 1, 10, and 20 cm from the center of the FOV, respectively. Measured sensitivity at the center of the FOV (20.84 cps/kBq) was significantly higher than systems with reduced axial FOV. The peak noise-equivalent counting rate was 266.3 kcps at 20.8 kBq/ml, with a corresponding scatter fraction of 40.2%. The correction accuracy for count losses up to the peak noise-equivalent counting rate was 3.6%. For the 10-, 13-, 17-, 22-, 28-, and 37-mm spheres, contrast recoveries in the image quality phantom were measured to be 46.2%, 54.3%, 66.1%, 71.1%, 85.3%, and 89.3%, respectively. The mean energy and timing resolution were 9.55% and 381.7 ps, respectively. Phantom and patient images demonstrated excellent image quality, even at short acquisition times or low injected activity. CONCLUSION: Compared to other PET/CT models, the extended axial FOV improved the overall PET performance of the 5-ring GE Discovery MI scanner. This system offers the potential to reduce scan times or injected activities through increased sensitivity.

Comparison of Micro-Computed Tomography and Clinical Computed Tomography Protocols for Visualization of Nasal Cartilage Before Surgical Planning for Rhinoplasty.

IMPORTANCE: There is no imaging standard to model nasal cartilage for the planning of rhinoplasty procedures. Preoperative visualization of cartilage may improve objective evaluation of nasal deformities, surgical planning, and surgical reconstruction. OBJECTIVES: To evaluate the feasibility of visualizing nasal cartilage using high resolution micro-computed tomography (CT) compared with the criterion standard of pathologic findings in a cadaveric specimen and to evaluate its accuracy compared with various clinical CT protocols. DESIGN, SETTING, AND PARTICIPANTS: Anatomic study at the University of Washington using single human cadaveric nasal specimens performed from July 10, 2017, to March 30, 2018. INTERVENTIONS: A micro-CT acquisition with 60-micron resolution was obtained of a nasal specimen. The specimen was then scanned with 5 different clinical CT protocols to span both clinical care and machine limits. The specimen was then sectioned in 5-mm axial slices for pathologic analysis. MAIN OUTCOMES AND MEASURES: Micro-CT images were registered to pathologic specimen cross-sections using a graphite fiducial system. Cartilage substructures were manually segmented and analyzed. A library of matched images across the micro-CT and various clinical CT protocols was then developed. Region of interest analysis was performed for each of the cartilage structures and their boundaries on clinical CT protocols and micro-CT, with the outcome of mean (SD) density using Hounsfield units. RESULTS: A single human cadaveric nasal specimen was used to obtain the following results. Lower lateral cartilage, upper lateral cartilage, and septal cartilage were accurately delineated on the micro-CT images compared with pathologic findings. The mean absolute deviation from pathologic findings was 0.30 mm for septal cartilage thickness, 0.98 mm for maximal upper lateral cartilage length, and 1.40 mm for maximal lower lateral cartilage length. On clinical CT protocols, only septal cartilage was well discriminated from boundary. Higher radiation dose resulted in more accurate density measurements of cartilage, but it did not ultimately improve ability to discriminate cartilage. CONCLUSIONS AND RELEVANCE: The results of this anatomic study may represent a notable step toward advancing knowledge of the capabilities and pitfalls of nasal cartilage visualization on CT. Nasal cartilage visualization was feasible on the micro-CT compared with pathologic findings. Future research may further examine the barriers to accurately visualizing upper lateral cartilage and lower lateral cartilage, a prerequisite for clinical application. LEVEL OF EVIDENCE: NA.

Patient body motion correction for dynamic cardiac PET-CT by attenuation-emission alignment according to projection consistency conditions.

INTRODUCTION: Patient body motion is known to cause large deviations in the determination of myocardial blood flow (MBF) with errors exceeding 300%. Accurate correction for patient whole-body motion is still a largely unsolved problem in cardiac positron emission tomography (PET) imaging. OBJECTIVE: This study evaluated the efficacy of using Natterer's formulation of the Helgason-Ludwig consistency conditions on the two-dimensional Radon transform to align computed tomography to PET projection data in multiple time frames of a dynamic sequence for the purpose of frame-by-frame correction of rigid whole-body motion. METHODS: The correction algorithm was evaluated with digital NCAT phantoms using realistic noise added by the analytical simulator. Count rates used in the simulation were derived from clinical patient data. In addition, a proof of concept test using measured data with a cardiac torso phantom was conducted. RESULTS: Motion correction resulted in significant improvement in the accuracy of MBF estimates, especially for high count-rate acquisitions. Maximum errors for 2 cm of motion dropped from 325% to 25% and from 250% to 25% using global and regional partial-volume correction, respectively. Median MBF errors dropped from 33% to 4.5% and 27% to 3.8%, respectively. Importantly, the correction algorithm performed equally well to compensate for body motion in both early and late time frames. CONCLUSION: Cardiac PET-CT data used for attenuation correction (CTAC) alignment using projection consistency conditions was effective for reducing errors in MBF measurements due to simulated patient motion, and can be integrated into the image reconstruction workflow.

Protocols for Harmonized Quantification and Noise Reduction in Low-Dose Oncologic 18F-FDG PET/CT Imaging.

Oncologic 18F-FDG PET/CT acquisition and reconstruction protocols need to be optimized for both quantitative and detection tasks. To date, most studies have focused on either quantification or noise, leading to quantitative harmonization guidelines or appropriate noise levels. We developed and evaluated protocols that provide harmonized quantitation with optimal amounts of noise as a function of acquisition parameters and body mass. Methods: Multiple image acquisitions (n = 17) of the International Electrotechnical Commission/National Electrical Manufacturers Association PET image-quality phantom were performed with variable counting statistics. Phantom images were reconstructed with 3-dimensional ordered-subset expectation maximization (OSEM3D) and point-spread function (PSF) for harmonized quantification of the contrast recovery coefficient of the maximum pixel value (CRC max ). The lowest counting statistics that resulted in compliance with European Association of Nuclear Medicine recommendations for CRC max and CRC max variability were used as optimization metrics. Image noise in the liver of 48 typical oncologic 18F-FDG PET/CT studies was analyzed with OSEM3D and PSF harmonized reconstructions. We also evaluated 164 additional 18F-FDG PET/CT reconstructed list-mode images to derive analytic expressions that predict image quality and noise variability. Phantom-to-subject translational analysis was used to derive optimized acquisition and reconstruction protocols. Results: For harmonized quantitation levels, PSF reconstructions yielded decreased noise and lower CRC max variability than regular OSEM3D reconstructions, suggesting they could enable a decreased activity regimen for matched performance. Conclusion: PSF reconstruction with a 7-mm postprocessing filter can provide harmonized quantification performance and acceptable image noise levels with injected activity, duration, and mass settings using a 260 MBq⋅s/kg acquisition parameter at scan time. Similarly, OSEM3D with a 5-mm postprocessing filter can provide similar performance with 401 MBq⋅s/kg.

Establishment of normative values for the fetal posterior fossa by magnetic resonance imaging.

OBJECTIVE: Suspected Dandy-Walker continuum anomalies constitute a significant percentage of prenatal cases evaluated by magnetic resonance imaging (MRI). To unify the description of posterior fossa malformations, we sought to establish objective measurements for the posterior fossa in normal fetuses between 18 and 37 weeks gestation. METHODS: T2-weighted images of normal fetal brains in sagittal projection were obtained from fetal magnetic resonance (MR) studies of normal brains performed from 2009 to 2017.121 fetal brains were included in the analysis. Three radiologists reviewed images and recorded the following for each case: superior posterior fossa angle (SPFA), posterior fossa perimeter, and tegmento-vermian angle (TVA). RESULTS: For each feature, the mean of the measurements, the percentage of absolute difference of the reader measurement compared with mean measurement, and the interclass correlation (ICC) were calculated. Values are reported as mean ± standard deviation. Perimeter increases linearly with age, whereas the SPFA and the TVA are independent of gestational age. For all included cases, the SPFA averaged 100.9° ± 8° and the TVA averaged 2.5° ± 2.3°. CONCLUSION: The superior posterior fossa angle, a novel measurement, and the posterior fossa perimeter can be used for establishing the expected size of the posterior fossa in second- and third-trimester fetuses by MRI.

CT Detectability of Small Low-Contrast Hypoattenuating Focal Lesions: Iterative Reconstructions versus Filtered Back Projection.

Purpose To investigate performance in detectability of small (≤1 cm) low-contrast hypoattenuating focal lesions by using filtered back projection (FBP) and iterative reconstruction (IR) algorithms from two major CT vendors across a range of 11 radiation exposures. Materials and Methods A low-contrast detectability phantom consisting of 21 low-contrast hypoattenuating focal objects (seven sizes between 2.4 and 10.0 mm, three contrast levels) embedded into a liver-equivalent background was scanned at 11 radiation exposures (volume CT dose index range, 0.5-18.0 mGy; size-specific dose estimate [SSDE] range, 0.8-30.6 mGy) with four high-end CT platforms. Data sets were reconstructed by using FBP and varied strengths of image-based, model-based, and hybrid IRs. Sixteen observers evaluated all data sets for lesion detectability by using a two-alternative-forced-choice (2AFC) paradigm. Diagnostic performances were evaluated by calculating area under the receiver operating characteristic curve (AUC) and by performing noninferiority analyses. Results At benchmark exposure, FBP yielded a mean AUC of 0.79 ± 0.09 (standard deviation) across all platforms which, on average, was approximately 2% lower than that observed with the different IR algorithms, which showed an average AUC of 0.81 ± 0.09 (P = .12). Radiation decreases of 30%, 50%, and 80% resulted in similar declines of observer detectability with FBP (mean AUC decrease, -0.02 ± 0.05, -0.03 ± 0.05, and -0.05 ± 0.05, respectively) and all IR methods investigated (mean AUC decrease, -0.00 ± 0.05, -0.04 ± 0.05, and -0.04 ± 0.05, respectively). For each radiation level and CT platform, variance in performance across observers was greater than that across reconstruction algorithms (P = .03). Conclusion Iterative reconstruction algorithms have limited radiation optimization potential in detectability of small low-contrast hypoattenuating focal lesions. This task may be further complicated by a high degree of variation in radiologists' performances, seemingly exceeding real performance differences among reconstruction algorithms. © RSNA, 2018 Online supplemental material is available for this article.

Hepatotoxic Dose Thresholds by Positron-Emission Tomography After Yttrium-90 Radioembolization of Liver Tumors: A Prospective Single-Arm Observational Study.

PURPOSE: To define a threshold radiation dose to non-tumoral liver from 90Y radioembolization that results in hepatic toxicity using pair-production PET. MATERIALS AND METHODS: This prospective single-arm study enrolled 35 patients undergoing radioembolization. A total of 34 patients (27 with HCC and 7 with liver metastases) were included in the final analysis. Of 27 patients with underlying cirrhosis, 22 and 5 patients were Child-Pugh A and B, respectively. Glass and resin microspheres were used in 32 (94%) and 2 (6%) patients, respectively. Lobar and segmental treatment was done in 26 (76%) and 8 (24%) patients, respectively. Volumetric analysis was performed on post-radioembolization time-of-flight PET imaging to determine non-tumoral parenchymal dose. Hepatic toxicity was evaluated up to 120 days post-treatment, with CTCAE grade ≤ 1 compared to grade ≥ 2. RESULTS: The median dose delivered to the non-tumoral liver in the treated lobe was 49 Gy (range 0-133). A total of 15 patients had grade ≤ 1 hepatic toxicity, and 19 patients had grade ≥ 2 toxicity. Patients with a grade ≥ 2 change in composite toxicity (70.7 vs. 43.8 Gy), bilirubin (74.1 vs. 43.3 Gy), albumin (84.2 vs. 43.8 Gy), and AST (94.5 vs. 47.1 Gy) have significantly higher non-tumoral parenchymal doses than those with grade ≤ 1. Liver parenchymal dose and Child-Pugh status predicted grade ≥ 2 toxicity, observed above a dose threshold of 54 Gy. CONCLUSION: Increasing delivered 90Y dose to non-tumoral liver measured by internal pair-production PET correlates with post-treatment hepatic toxicity. The likelihood of toxicity exceeds 50% at a dose threshold of 54 Gy. ClinicalTrials.gov identifier: NCT02848638.

Quantitative myocardial perfusion from static cardiac and dynamic arterial CT.

Quantitative myocardial blood flow (MBF) estimation by dynamic contrast enhanced cardiac computed tomography (CT) requires multi-frame acquisition of contrast transit through the blood pool and myocardium to inform the arterial input and tissue response functions. Both the input and the tissue response functions for the entire myocardium are sampled with each acquisition. However, the long breath holds and frequent sampling can result in significant motion artifacts and relatively high radiation dose. To address these limitations, we propose and evaluate a new static cardiac and dynamic arterial (SCDA) quantitative MBF approach where (1) the input function is well sampled using either prediction from pre-scan timing bolus data or measured from dynamic thin slice 'bolus tracking' acquisitions, and (2) the whole-heart tissue response data is limited to one contrast enhanced CT acquisition. A perfusion model uses the dynamic arterial input function to generate a family of possible myocardial contrast enhancement curves corresponding to a range of MBF values. Combined with the timing of the single whole-heart acquisition, these curves generate a lookup table relating myocardial contrast enhancement to quantitative MBF. We tested the SCDA approach in 28 patients that underwent a full dynamic CT protocol both at rest and vasodilator stress conditions. Using measured input function plus single (enhanced CT only) or plus double (enhanced and contrast free baseline CT's) myocardial acquisitions yielded MBF estimates with root mean square (RMS) error of 1.2 ml/min/g and 0.35 ml/min/g, and radiation dose reductions of 90% and 83%, respectively. The prediction of the input function based on timing bolus data and the static acquisition had an RMS error compared to the measured input function of 26.0% which led to MBF estimation errors greater than threefold higher than using the measured input function. SCDA presents a new, simplified approach for quantitative perfusion imaging with an acquisition strategy offering substantial radiation dose and computational complexity savings over dynamic CT.

Prospective Trial Using Internal Pair-Production Positron Emission Tomography to Establish the Yttrium-90 Radioembolization Dose Required for Response of Hepatocellular Carcinoma.

PURPOSE: To prospectively assess the threshold dose for objective response of hepatocellular carcinoma (HCC), using 90Y internal pair-production positron emission tomography (PET) to quantify the radiation dose delivered to hepatic tumors after radioembolization. METHODS AND MATERIALS: A prospective study was performed under institutional review board approval from 2012 to 2014. Thirty-five patients with primary and secondary liver tumors undergoing 90Y treatment were recruited. Eight patients did not meet inclusion criteria, and 27 patients with HCC were included for analysis. Time-of-flight PET imaging was performed immediately after radioembolization and voxel values converted into 90Y activity. The radioembolization dose was calculated from PET images, and image segmentation was performed with volumetric analysis of dose deposition within tumors. Radiographic response was assessed on follow-up imaging. RESULTS: Treated HCC showed 84% objective response, 11% stable disease, and 5% progressive disease according to modified RECIST 1.1 response criteria. Responders had a higher median 90Y tumor dose than nonresponders (225 Gy vs 83 Gy, P < .01). Logistic regression models show tumor dose (P = .002) strongly predicted objective response. All nonresponders had tumor dose <200 Gy. No statistical difference for patient age, tumor volume, multifocal or extrahepatic disease, portal vein invasion, or injected 90Y activity was found between responders and nonresponders. CONCLUSIONS: Hepatocellular carcinoma that resulted in objective response after radioembolization had a greater median tumor dose of 225 Gy, compared with 83 Gy in nonresponders. Delivered tumor dose can be assessed by PET and significantly impacts treatment response in HCC.

Variable temporal sampling and tube current modulation for myocardial blood flow estimation from dose-reduced dynamic computed tomography.

Quantification of myocardial blood flow (MBF) can aid in the diagnosis and treatment of coronary artery disease. However, there are no widely accepted clinical methods for estimating MBF. Dynamic cardiac perfusion computed tomography (CT) holds the promise of providing a quick and easy method to measure MBF quantitatively. However, the need for repeated scans can potentially result in a high patient radiation dose, limiting the clinical acceptance of this approach. In our previous work, we explored techniques to reduce the patient dose by either uniformly reducing the tube current or by uniformly reducing the number of temporal frames in the dynamic CT sequence. These dose reduction techniques result in noisy time-attenuation curves (TACs), which can give rise to significant errors in MBF estimation. We seek to investigate whether nonuniformly varying the tube current and/or sampling intervals can yield more accurate MBF estimates for a given dose. Specifically, we try to minimize the dose and obtain the most accurate MBF estimate by addressing the following questions: when in the TAC should the CT data be collected and at what tube current(s)? We hypothesize that increasing the sampling rate and/or tube current during the time frames when the myocardial CT number is most sensitive to the flow rate, while reducing them elsewhere, can achieve better estimation accuracy for the same dose. We perform simulations of contrast agent kinetics and CT acquisitions to evaluate the relative MBF estimation performance of several clinically viable variable acquisition methods. We find that variable temporal and tube current sequences can be performed that impart an effective dose of 5.5 mSv and allow for reductions in MBF estimation root-mean-square error on the order of 20% compared to uniform acquisition sequences with comparable or higher radiation doses.