Lesion Standardized Uptake Value Research Articles

Energy-based scatter estimation in clinical PET.

Scatter correction (SC) is essential in PET for accurate quantitative imaging. The state-of-the-art SC method is single-scatter simulation (SSS). Although this method is usually robust and accurate, it can fail in some situations, for example when there is motion between the CT and PET scans in PET/CT. Therefore, it is of interest to consider other SC methods. In this work, an energy-based scatter estimation (EBS) method is described in detail, tested in phantoms and patients, and compared to SSS. This version of EBS was developed for list-mode data from Biograph Vision-600 PET/CT scanner. EBS is based on digitized 2D energy histograms in each bin of a coarsely sampled PET sinogram, either with or without time of flight (TOF). The histograms are modeled as a noisy realization of a linear combination of nine basis functions whose parameters were derived from a measurement of the 511-keV photopeak spectrum as well as Monte-Carlo simulations of the scattering process. EBS uses an iterative expectation maximization approach to determine the coefficients in the linear combination, and from this estimates the scatter. The investigation was restricted to 18 F-based PET data in which the acquired number of counts was similar to the levels seen in oncological whole-body PET/CT scans. To evaluate the performance, phantom scans were used that involved the NEMA NU2-2018 protocol, a slab phantom, an NU 2-1994 phantom, a cardiac phantom in an anthropomorphic chest phantom, and a uniformly-filled torso phantom with a bladder phantom slightly outside the axial field of view. Contrast recovery (CR) and other parameters were evaluated in images reconstructed with SSS and EBS. Furthermore, FDG PET scans of seven lung cancer patients were used in the evaluation. Standardized uptake values (SUV) based on SSS and EBS were compared in 27 lesions. EBS and SSS images were visually similar in all cases except the torso + bladder phantom, where the EBS was much closer to the expected uniform image. The NU2-2018 analysis indicated a 2% scatter residual in EBS images compared to 3% with SSS, and 10% higher background variability, which is a surrogate for image noise. The cardiac phantom scan showed that CR was 98.2% with EBS and 99.6% with SSS, and that the SSS sinogram had values greater than the net-true emission sinogram, indicating a slight overcorrection in the case of SSS. In the lesion SUV comparison in patient scans, EBS correlated strongly (R2 =0.9973) with SSS, and SUV based on EBS were systematically 0.1 SUV lower. In the case of the torso + bladder phantom portion, the SSS image of the torso + bladder phantom was 299% times hotter than expected in one area, due to scatter estimation error, compared to 16% colder with EBS. In evaluating clinically relevant parameters such as SUV in focal lesions, EBS and SSS give almost the same results. In phantoms, some scatter figures of merit were slightly improved by use of EBS, though an image variability figure of merit was slightly degraded. In typical oncological whole-body PET/CT, EBS may be a suitable replacement for SSS, especially when SSS fails due to technical problems during the scan.

JS09.5.A18F-FLUCICLOVINE PET FOR DETECTION OF RECURRENT BRAIN METASTASES AFTER RADIATION THERAPY: IMAGE INTERPRETATION CRITERIA RESULTS FROM PURSUE, A PROSPECTIVE PHASE 2 TRIAL

Abstract BACKGROUND Differentiating radiation necrosis from tumour progression after radiation therapy (RT) for brain metastases (BM) remains clinically challenging, and accurate imaging is crucial to prevent unnecessary surgery or unwarranted changes in therapy. 18F-Fluciclovine is a PET radiopharmaceutical with low background uptake in the brain and increased uptake in BM. The PURSUE study (NCT04410367) aimed to establish image interpretation criteria (IIC) for detecting suspected recurrent BM after RT using 18F-fluciclovine PET, based on several measures of lesion uptake. MATERIAL AND METHODS Across 7 US sites, 23 patients with solid tumour BM and a previously irradiated ‘reference’ lesion equivocal for recurrence on MRI who were scheduled for craniotomy underwent 18F-fluciclovine PET (185 MBq) <42 days post-MRI and 1-21 days pre-craniotomy. Three independent, blinded readers qualitatively rated lesion 18F-fluciclovine uptake as ‘mild’ (up to blood pool), ‘moderate’ (above blood pool to parotid gland), or ‘marked’ (above parotid gland). The primary endpoint was the diagnostic performance of different thresholds of lesion uptake on qualitative (visual) reads vs central histopathology. Secondary endpoints included diagnostic performance, based on different thresholds, of quantitative (e.g., lesion standardized uptake value [SUV]), and dynamic measures. A committee, including two independent imaging physicians, reviewed all data to establish the IIC, which were subsequently used to evaluate the diagnostic performance of 18F-fluciclovine. RESULTS All 23 reference lesions underwent histopathological analysis, with 10 (43%) being pathologically confirmed BM recurrence. The highest performing qualitative measure of 18F-fluciclovine lesion uptake was ‘marked’, rendering 92-100% and variable (40-80%) across readers. SUVmax was a reader-independent, high-performing quantitative metric (AUC 0.87, SUVmax threshold 4.8, 80% sensitivity, 85% specificity). Dynamic measures did not add diagnostic value. Thus, the committee established IIC as: "Lesions with 18F-fluciclovine uptake of a SUVmax equal to or greater than 4.8, or visually greater than the parotid gland, should be considered suspicious for recurrence. Otherwise, recurrence should be considered unlikely." Application of these IIC resulted in 80% sensitivity, 77-85% specificity, 73-80% positive predictive value, and 83-85% negative predictive value across readers. CONCLUSION PURSUE is the first prospective, multicentre study to define IIC for 18F-fluciclovine PET for accurate identification of suspected recurrent BM after RT, verified by histopathology. In this initial cohort, the IIC convey excellent diagnostic performance for 18F-fluciclovine and will help evaluate 18F-fluciclovine PET in future studies. This study was sponsored by Blue Earth Diagnostics Ltd.

NEIM-05 PURSUE: RESULTS FROM A PROSPECTIVE, PHASE 2B TRIAL TO DEFINE IMAGE INTERPRETATION CRITERIA FOR18F-FLUCICLOVINE-PET FOR DETECTION OF RECURRENT BRAIN METASTASES AFTER RADIATION THERAPY

Abstract BACKGROUND After radiation therapy (RT) for brain metastases (BM), differentiating radiation necrosis from tumor recurrence remains challenging. PURSUE (NCT04410367) evaluated various measures of lesion 18F-fluciclovine uptake to establish image interpretation criteria (IIC) for 18F-fluciclovine-PET to accurately diagnose recurrent BM. METHODS Patients with solid tumor BM and a previously irradiated ‘reference’ lesion equivocal for recurrence on MRI who were scheduled for craniotomy underwent 18F-fluciclovine-PET (185 MBq) <42 days post-MRI and 1-21 days pre-craniotomy. Lesion 18F-fluciclovine uptake was qualitatively rated as ‘mild’ (up to blood pool), ‘moderate’ (above blood pool to parotid gland), or ‘marked’ (above parotid gland) by three independent blinded readers. The primary endpoint was diagnostic performance of different uptake thresholds on qualitative reads vs central histopathology. Secondary endpoints included diagnostic performance, based on different thresholds, of quantitative (e.g., lesion standardized uptake value [SUV]) and dynamic measures. IIC were determined by committee and subsequently used to assess the diagnostic performance of 18F-fluciclovine. RESULTS All 23 reference lesions from 23 enrolled patients underwent histopathological analysis; 10 (43%) were pathologically-confirmed BM recurrence. The highest performing qualitative measure was ‘marked’, rendering 92-100% sensitivity and 40-80% specificity across readers. SUVmax was a reader-independent, high-performing quantitative metric (AUC 0.87, SUVmax threshold 4.8, 80% sensitivity, 85% specificity). Dynamic measures did not add diagnostic value. Thus, IIC was established as: “Lesions with 18F-fluciclovine uptake of SUVmax equal to or greater than 4.8, or visually greater than the parotid gland, should be considered suspicious for recurrence. Otherwise, recurrence should be considered unlikely.” Application of the IIC resulted in 80% sensitivity, 77-85% specificity, 73-80% PPV, and 83-85% NPV across the readers. CONCLUSIONS PURSUE is the first prospective, multicenter trial to establish IIC for 18F-fluciclovine-PET for suspected recurrent BM after RT, verified by histopathology. Finalized IIC demonstrated excellent diagnostic performance for 18F-fluciclovine and will help evaluate 18F-fluciclovine-PET in future studies.

Maximum and mean standardized uptake values of medication-related osteonecrosis of the jaw with bone SPECT/CT: comparison of mandibular pathologies, control and temporomandibular joints.

Recently, single-photon emission CT/CT (SPECT/CT) plays an important role in assessing patients with medication-related osteonecrosis of the jaw (MRONJ). The aim of this study was to investigate maximum and mean standardized uptake values (SUVs) of MRONJ with bone SPECT/CT, especially comparison of mandibular pathologies, control and temporomandibular joints. 61 mandibular patients with MRONJ who underwent bone SPECT/CT were included in this study. The maximum and mean SUVs of the lesion, right and left sides of the lesion, opposite side of the lesion as control, right and left temporomandibular joints were analyzed using a workstation and software. The SUVs of MRONJ were analyzed using one-way analysis of variance with Tukey's honestly significant difference test. Patient characteristics with MRONJ and SUVs were analyzed using Mann-Whitney U test. P-values less than 0.05 were considered to indicate statistical significance. The maximum and mean SUVs for opposite side of the lesions (4.4 ± 2.0 and 1.8 ± 0.7) were significantly lower than those for mandibular lesions (18.3 ± 8.1 and 6.3 ± 2.8), right side of the lesions (8.1 ± 3.9 and 2.9 ± 1.3) and left side of the lesions (8.1 ± 3.9 and 2.8 ± 1.4), respectively. The maximum and mean SUVs for right and left sides of the lesions, and opposite side of the lesions, right and left temporomandibular joints were not significant difference. Furthermore, the maximum SUVs of the mandibular lesions were a significant difference for age and staging. The maximum and mean SUVs with SPECT/CT can be useful in the quantitative management of MRONJ patients.

Anatomically guided reconstruction improves lesion quantitation and detectability in bone SPECT/CT.

Bone single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging suffers from poor spatial resolution, but the image quality can be improved during SPECT reconstruction by using anatomical information derived from CT imaging. The purpose of this work was to compare two different anatomically guided SPECT reconstruction methods to ordered subsets expectation maximization (OSEM) which is the most commonly used reconstruction method in nuclear medicine. The comparison was done in terms of lesion quantitation and lesion detectability. Anatomically guided Bayesian reconstruction (AMAP) and kernelized ordered subset expectation maximization (KEM) algorithms were implemented and compared against OSEM. Artificial lesions with a wide range of lesion-to-background contrasts were added to normal bone SPECT/CT studies. The quantitative accuracy was assessed by the error in lesion standardized uptake values and lesion detectability by the area under the receiver operating characteristic curve generated by a non-prewhitening matched filter. AMAP and KEM provided significantly better quantitative accuracy than OSEM at all contrast levels. Accuracy was the highest when SPECT lesions were matched to a lesion on CT. Correspondingly, AMAP and KEM also had significantly better lesion detectability than OSEM at all contrast levels and reconstructions with matching CT lesions performed the best. Quantitative differences between AMAP and KEM algorithms were minor. Visually AMAP and KEM images looked similar. Anatomically guided reconstruction improves lesion quantitation and detectability markedly compared to OSEM. Differences between AMAP and KEM algorithms were small and thus probably clinically insignificant.

Dynamic PET/CT scan of 68Ga-FAPI-04 for the optimal acquisition time in suspected malignant hepatic cancer patients.

Dynamic PET/CT scan of 68Ga-FAPI-04 in patients with suspected malignant hepatic lesions were retrospectively analyzed to find the optimal acquisition time with better lesion detection rate. Twenty-two patients with lesions confirmed by CT or MRI were performed with dynamic 68Ga-FAPI-04 PET/CT scan. Tracer uptake of lesions and normal organs at different time points were analyzed. Standardized uptake value (SUV) and tumor-to-background (TBR) were calculated based on the quantification of images. SUV of normal organs decreased rapidly from 10 to 30min and decreased gradually from 30 to 60min. Besides, the uterus showed a particularly high uptake in all patients (12.62 ± 4.58 at 10min p.i., 12.04 ± 3.99 at 30min p.i., 10.92 ± 2.38 at 60min p.i.). SUV of lesions decreased gradually, while TBR increased from 10- to 60-min post-injection. Visual analysis verified a comparable lesion detectability of 30min and 60min with images of 10min showing a decreased lesion detection number. This study revealed that similar detection rates were achieved at both 30 and 60min, suggesting a static scan at 30min to be appropriate in the clinic. Besides, although with high lesion uptake, early 68Ga-FAPI-04 PET imaging at 10min after tracer injection could cause missed lesion detection.

Clinical features and treatment outcomes of pulmonary actinomycosis.

Pulmonary actinomycosis is a rare and chronic infectious disease that mimics malignancy and is frequently misdiagnosed. There are few reports that address the clinical characteristics of pulmonary actinomycosis. The objective of this research is to evaluate the clinical features, radiological findings, diagnostic approaches and treatment outcomes of pulmonary actinomycosis. Thirty-seven patients with pulmonary actinomycosis histopathologically diagnosed from 2009 to 2021 were analyzed retrospectively. The mean age at presentation was 53.7 (±13.3) years. Frequent symptoms were cough and hemoptysis. The median diagnosis time from the first symptoms was 60 days (interquartile range 18-195). Pulmonary comorbidity was found in 59.5% of cases. The most common thorax computed tomography finding was mass or nodule. The low-attenuation center within the mass or consolidation was observed in 40% of the lesions. The median maximal standardized uptake value of lesions on positron emission tomography (PET) was 6.5 (interquartile range 2.7-10.3). In the majority of cases (97.3%), the diagnosis of pulmonary actinomycosis was not suspected at admission, and 56.8% of patients were misdiagnosed with lung cancer. The mean duration of antibiotic therapy was 9.4 days (range 3-22) with intravenous antibiotics and 64.7 days (range 5-270) with oral antibiotics. Four patients died due to concomitant comorbidities. Eight cases were lost to follow-up. All other cases were fully cured. Pulmonary actinomycosis mimics other diseases, often lung cancer. Clinicians should consider the diagnosis of actinomycosis when they detect a mass or consolidation, especially with a low-attenuation center. PET/CT appears not to be useful for differential diagnosis. A shorter course of antibiotic therapy than traditionally recommended appears to be sufficient.

Harmonization based on quantitative analysis of standardized uptake value variations across PET/CT scanners: a multicenter phantom study.

This study aimed to measure standardized uptake value (SUV) variations across different PET/computed tomography (CT) scanners to harmonize quantification across systems. We acquired images using the National Electrical Manufacturers Association International Electrotechnical Commission phantom from three PET/CT scanners operated using routine imaging protocols at each site. The SUVs of lesions were assessed in the presence of reference values by a digital reference object (DRO) and recommendations by the European Association of Nuclear Medicine (EANM/EARL) to measure inter-site variations. For harmonization, Gaussian filters with tuned full width at half maximum (FWHM) values were applied to images to minimize differences in SUVs between reference and images. Inter-site variation of SUVs was evaluated in both pre- and postharmonization situations. Test-retest analysis was also carried out to evaluate repeatability. SUVs from different scanners became significantly more consistent, and inter-site differences decreased for SUV mean , SUV max and SUV peak from 17.3, 20.7, and 15.5% to 4.8, 4.7, and 2.7%, respectively, by harmonization ( P values <0.05 for all). The values for contrast-to-noise ratio in the smallest lesion of the phantom verified preservation of image quality following harmonization (>2.8%). Harmonization significantly lowered variations in SUV measurements across different PET/CT scanners, improving reproducibility while preserving image quality.

Volumetric analysis of mandibular lesions with SPECT/CT: a pilot clinical study of maximum standardized uptake value.

PurposeThis study was designed to investigate mandibular lesions using volumetric analysis with bone single-photon emission computed tomography/computed tomography (SPECT/CT).Material and methodsEight patients with mandibular lesions underwent SPECT/CT scan acquisition 4 hours after injection of Tc-99m hydroxymethylene diphosphonate (HMDP). Regarding volumetric analysis, maximum standar-dized uptake value (SUV) was obtained using software and a workstation (Q.Volumetrix MI and GEniE-Xeleris 4 DR, respectively). The localization and size of the volume of interest (VOI) can be drawn over the lesion, mesial, distal, and opposite side as normal using the CT, SPECT, and SPECT/CT transaxials, coronals, and sagittals as the anatomical reference. Q.Volumetrix MI can analyse SUV of lesions by organ segmentation using optional pan and zoom imaging. Then, the dosimetry software provided multiple quantitative data for a given VOI. Statistical analyses for the maximum SUV were performed by Mann-Whitney U test. A p-value lower than 0.05 was considered as statistically significant.ResultsMaximum SUVs for medication-related osteonecrosis of the jaw (n = 4, 25.4 ± 4.9), chronic osteomyelitis (n = 3, 14.6 ± 3.1), and squamous cell carcinoma (n = 1, 31.7) were significantly higher than those of the opposite side as normal mandible (3.8 ± 0.7, 4.6 ± 1.8, and 7.4, respectively; p = 0.000).ConclusionsVolumetric analysis with SPECT/CT could be useful for the evaluation of mandibular lesions, such as detecting and surgical planning.

Measuring Heterogeneity in 18F-Fluorodeoxyglucose Positron Emission Tomography Images for Classifying Metastatic and Benign Bone Lesions in Patients with Cervical Cancer

PurposeHeterogeneity assessment can be applied for medical imaging analysis. Here, we evaluated first-order and texture analysis (TA) metrics in 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) imaging for classification of metastatic and benign bone lesions in patients with cervical cancer.MethodsThe data of 18F-FDG PET studies performed on a specific PET/CT system from 2016 to 2018 in patients with cervical cancer were retrieved. The data of bone lesions extracted from studies over 2016–2017 and 2018 were used as training and validation datasets, respectively. Metastatic bone lesions were identified in each dataset, with an equal number of benign bone lesions selected. Cuboid volume of interest (VOI) consisting of 3 × 3 × 5 reconstructed voxels was applied for first-order metrics, and cubic VOI consisting of smaller voxels with trilinear interpolation of standardized uptake value (SUV) was adopted for TA metrics. First-order metrics included the maximum SUV (SUVmax) of lesions and the mean voxel SUV and its standard deviation (SUVsd), skewness, and kurtosis in VOI. In total, 4464 TA metrics based on 62 texture features were evaluated. Logistic regression was used for classification with area under the receiver operating characteristic curve (AUC) as the performance measure.ResultsFrom the training and validation datasets, 98 and 42 metastatic bone lesions were identified, respectively. SUVsd demonstrated higher performance than did SUVmax in both the training (AUC .798 vs .732, P = .001) and validation (AUC .786 vs .684, P < .001) datasets. Top-performing TA metrics demonstrated significantly higher performance in the training dataset, but not in the validation dataset.ConclusionA simple first-order measure of heterogeneity, SUVsd, was found to be superior to SUVmax for the classification of metastatic and benign bone lesions. Multiple hypothesis testing can result in false-positive findings in TA with multiple features and parameters; careful validation is required.

Integrated CT Radiomics Features Could Enhance the Efficacy of 18F-FET PET for Non-Invasive Isocitrate Dehydrogenase Genotype Prediction in Adult Untreated Gliomas: A Retrospective Cohort Study.

PurposeWe aimed to investigate the predictive models based on O-[2-(18F)fluoroethyl]-l-tyrosine positron emission tomography/computed tomography (18F-FET PET/CT) radiomics features for the isocitrate dehydrogenase (IDH) genotype identification in adult gliomas.MethodsFifty-eight consecutive pathologically confirmed adult glioma patients with pretreatment 18F-FET PET/CT were retrospectively enrolled. One hundred and five radiomics features were extracted for analysis in each modality. Three independent radiomics models (PET-Rad Model, CT-Rad Model and PET/CT-Rad Model) predicting IDH mutation status were generated using the least absolute shrinkage and selection operator (LASSO) regression analysis based on machine learning algorithms. All-subsets regression and cross validation were applied for the filter and calibration of the predictive radiomics models. Besides, semi-quantitative parameters including maximum, peak and mean tumor to background ratio (TBRmax, TBRpeak, TBRmean), standard deviation of glioma lesion standardized uptake value (SUVSD), metabolic tumor volume (MTV) and total lesion tracer uptake (TLU) were obtained and filtered for the simple model construction with clinical feature of brain midline involvement status. The area under the receiver operating characteristic curve (AUC) was applied for the evaluation of the predictive models.ResultsThe AUC of the simple predictive model consists of semi-quantitative parameter SUVSD and dichotomized brain midline involvement status was 0.786 (95% CI 0.659-0.883). The AUC of PET-Rad Model building with three 18F-FET PET radiomics parameters was 0.812 (95% CI 0.688-0.902). The AUC of CT-Rad Model building with three co-registered CT radiomics parameters was 0.883 (95% CI 0.771-0.952). While the AUC of the combined 18F-FET PET/CT-Rad Model building with three CT and one PET radiomics features was 0.912 (95% CI 0.808-0.970). DeLong test results indicated the PET/CT-Rad Model outperformed the PET-Rad Model (p = 0.048) and simple predictive model (p = 0.034). Further combination of the PET/CT-Rad Model with the clinical feature of dichotomized tumor location status could slightly enhance the AUC to 0.917 (95% CI 0.814-0.973).ConclusionThe predictive model combining 18F-FET PET and integrated CT radiomics features could significantly enhance and well balance the non-invasive IDH genotype prediction in untreated gliomas, which is important in clinical decision making for personalized treatment.

Radiomic Phenotypes of High and Low Lesion SUV Components for the Prediction of Refractory Disease in Hodgkin's Lymphoma Patients Treated with ABVD Based Therapy

Background: Hodgkin's lymphoma (HL) is a curable malignancy. However, some patients are refractory to frontline therapy. Early prediction of response to frontline therapy could identify patients who may benefit from more intensive therapy. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has an established role in the management of HL. Radiomic features provide a way of quantifying imaging phenotypes and have shown promising results as predictors of outcomes in different lymphomas. Furthermore, great interest has been focused on the heterogeneity of standardized uptake value (SUV) within a single lesion. Since high SUV component (HSc) and low-SUV component (LSc) regions within a single lesion may be associated with different phenotypical characteristics, the radiomic analysis for each regional SUV component may provide a more complete description of lesions. Therefore, we proposed and evaluated new descriptors to quantify the image phenotypes based on HSc and LSc of lesions in HL.Methods: A total of 61 patients with HL of all stages who were seen at MD Anderson Cancer Center between 2016 and 2020 and had analyzable pre-treatment PET/CT were selected. All patients received standard of care ABVD or AVD regimens with or without radiation (Table 1A). Pre-treatment PET/CT scans were analyzed, and HL lesions were semi-automatically segmented using MIM 7 (Cleveland, OH) based on a SUV max threshold of 2.5. Manual edits were made and reviewed by a nuclear medicine physician and a lymphoma specialist. A total of 110 radiomic features were extracted from the segmented lesions in CT and PET using the open-source package of ‘PyRadiomics’ (Table 1B).Detailed description and algorithms of the extracted radiomics features are available at https://pyradiomics.readthedocs.io/en/latest/features.html. Additionally, each lesion was partitioned into HSc and LSc based on a cutoff value of 3 times the liver SUV mean (Figure A). The ratio of features between SUV components (HSc, LSc) and the lesion area was calculated. Furthermore, the feature difference between HSc and LSc was obtained.The maximum, minimum, average, and standard deviation of the radiomic features within multiple lesions were computed to reveal the distribution of features. A sequential forward feature selection was applied to select the significant features for building a logistic regression model, to predict refractory disease according to Lugano criteria. Two logistic regression models were constructed for early and advanced stage patients. Quantitative measures, namely metabolic tumor volume (MTV), total lesion glycolysis (TLG), and SUV max were measured for comparison. The leave-one-out-cross-validation (LOOCV) was applied to yield the receiver-operator-characteristics curve; the area under the curve (AUC) was then computed to evaluate the performance of the proposed model compared to quantitative measurements using DeLong's test.Results: The average of small dependence high gray level emphasis (GLDM) from PET, the difference of major axis length between high- and low- SUV component from PET, and the difference of 10th Percentile (histogram) between high- and low- SUV component from PET were selected for identifying the refractory disease in early stage lesions; the maximum of correlation (GLCM) from PET, SD of small dependence emphasis (GLDM) from PET, and SD of the inverse difference moment normalized (GLCM) from PET were selected for identifying refractory disease in advanced stage lesions. Based on LOOCV, the proposed radiomics model achieved an AUC of 0.93 for refractory disease prediction, which was significantly superior to MTV (AUC, 0.66; P = 0.01), TLG (AUC, 0.64; P = 0.01), and SUV max (AUC, 0.61; P = 0.01) (Figure B)Conclusion: High and low SUV components-based radiomic model of PET/CT was potentially useful for upfront prediction of refractory HL. Validation in a larger cohort using different segmentation methods, inclusion of additional treatment subgroups, comparison to other predictors, and correlation with survival outcomes are underway. [Display omitted] DisclosuresAhmed: Seagen: Research Funding; Merck: Research Funding; Tessa Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Xencor: Research Funding. Steiner: BMS: Research Funding; Seattle Genetics: Research Funding; Rafael Pharmaceuticals: Research Funding. Pinnix: Merck Inc: Research Funding. Wang: Molecular Templates: Research Funding; The First Afflicted Hospital of Zhejiang University: Honoraria; Hebei Cancer Prevention Federation: Honoraria; Bayer Healthcare: Consultancy; Mumbai Hematology Group: Honoraria; Pharmacyclics: Consultancy, Research Funding; BioInvent: Research Funding; Celgene: Research Funding; Physicians Education Resources (PER): Honoraria; Miltenyi Biomedicine GmbH: Consultancy, Honoraria; Scripps: Honoraria; Janssen: Consultancy, Honoraria, Research Funding; Imedex: Honoraria; Dava Oncology: Honoraria; Epizyme: Consultancy, Honoraria; Clinical Care Options: Honoraria; BGICS: Honoraria; CAHON: Honoraria; VelosBio: Consultancy, Research Funding; Loxo Oncology: Consultancy, Research Funding; InnoCare: Consultancy, Research Funding; BeiGene: Consultancy, Honoraria, Research Funding; Anticancer Association: Honoraria; Genentech: Consultancy; AstraZeneca: Consultancy, Honoraria, Research Funding; CStone: Consultancy; Newbridge Pharmaceuticals: Honoraria; Juno: Consultancy, Research Funding; Acerta Pharma: Consultancy, Honoraria, Research Funding; Chinese Medical Association: Honoraria; Kite Pharma: Consultancy, Honoraria, Research Funding; Oncternal: Consultancy, Research Funding; DTRM Biopharma (Cayman) Limited: Consultancy; OMI: Honoraria; Moffit Cancer Center: Honoraria; Lilly: Research Funding.

Aberrant patterns of PET response during treatment for DLBCL patients with MYC gene rearrangements

PurposeMYC gene rearrangements in diffuse large B-cell lymphoma (DLBCL) patients are associated with poor prognosis. Our aim was to compare patterns of 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography computed tomography (PET/CT) response in MYC + and MYC- DLBCL patients.MethodsInterim PET/CT (I-PET) and end of treatment PET/CT (EoT-PET) scans of 81 MYC + and 129 MYC- DLBCL patients from 2 HOVON trials were reviewed using the Deauville 5-point scale (DS). DS1-3 was regarded as negative and DS4-5 as positive. Standardized uptake values (SUV) and metabolic tumor volume (MTV) were quantified at baseline, I-PET, and EoT-PET. Negative (NPV) and positive predictive values (PPV) were calculated using 2-year overall survival.ResultsMYC + DLBCL patients had significantly more positive EoT-PET scans than MYC- patients (32.5 vs 15.7%, p = 0.004). I-PET positivity rates were comparable (28.8 vs 23.8%). In MYC + patients 23.2% of the I-PET negative patients converted to positive at EoT-PET, vs only 2% for the MYC- patients (p = 0.002). Nine (34.6%) MYC + DLBCL showed initially uninvolved localizations at EoT-PET, compared to one (5.3%) MYC- patient. A total of 80.8% of EoT-PET positive MYC + patients showed both increased lesional SUV and MTV compared to I-PET. In MYC- patients, 31.6% showed increased SUV and 42.1% showed increased MTV. NPV of I-PET and EoT-PET was high for both MYC subgroups (81.8–94.1%). PPV was highest at EoT-PET for MYC + patients (61.5%).ConclusionMYC + DLBCL patients demonstrate aberrant PET response patterns compared to MYC- patients with more frequent progression during treatment after I-PET negative assessment and new lesions at sites that were not initially involved.Trial registration number and date of registrationHOVON-84: EudraCT: 2006–005,174-42, retrospectively registered 01–08-2008. HOVON-130: EudraCT: 2014–002,654-39, registered 26–01-2015

18 Fluorine-fluorodeoxyglucose positron emission tomography for assessment of deep digital flexor tendinopathy: An exploratory study in eight horses with comparison to CT and MRI.

Lesions of the deep digital flexor tendon (DDFT) are a cause for foot lameness in horses. Positron emission tomography (PET) could provide valuable information regarding the metabolic activity of these lesions. The aims of this exploratory, prospective, methods comparison study were to assess the ability of 18 fluorine-fluorodeoxyglucose (18 F-FDG) PET to detect DDFT lesions and to compare the PET findings with CT and MRI findings. Eight horses with lameness due to pain localized to the front feet were included. Both front limbs of all horses were imaged with 18 F-FDG PET, noncontrast CT, and arterial contrast-enhanced CT; 11 limbs were also assessed using MRI. Two observers graded independently 18 F-FDG PET, noncontrast CT, arterial contrast CT, T1-weighted (T1-w) MRI, and T2-weighted (T2-w)/STIR MRI. Maximal standardized uptake values were measured. Lesions were found in seven of 16 DDFT on PET, 12 of 16 DDFT on noncontrast CT, six of 15 DDFT on arterial contrast CT, eight of 11 DDFT on T1-w MRI, and six of 11 DDFT on T2-w/STIR MRI. Positron emission tomography was in better agreement with arterial contrast CT (Kappa-weighted 0.40) and T2-w/STIR MRI (0.35) than with noncontrast CT (0.28) and T1-w MRI (0.20). Maximal standardized uptake values of lesions ranged from 1.9 to 4.6 with a median of 3.1. Chronic lesions with scar tissues identified on noncontrast CT or T1-w MRI did not have increased 18 F-FDG uptake. These results demonstrated that 18 F-FDG PET agreed more closely with modalities previously used to detect active tendon lesions, i.e. arterial contrast CT and T2-w/STIR MRI. 18 Fluorine-fluorodeoxyglucose PET can be used to identify metabolically active DDFT lesions in horses.

A Prediction Model to Optimize Invasive Mediastinal Staging Procedures for Non-small Cell Lung Cancer in Patients With a Radiologically Normal Mediastinum: The Quebec Prediction Model

Current guideline-recommended criteria for invasive mediastinal staging in patients with a radiologically normal mediastinum fail to identify a significant proportion of patients with occult mediastinal disease (OMD), despite it leading to a large number of invasive staging procedures. Which variables available before surgery predict the probability of OMD in patients with a radiologically normal mediastinum? We identified all cTxN0/N1M0 non-small cell lung cancer tumors staged by CT imaging and PET with CT imaging in our institution between 2014 and 2018 who underwent gold standard surgical lymph node dissection or were demonstrated to have OMD before surgery by invasive mediastinal staging techniques and divided them into a derivation and an independent validation cohort to create the Quebec Prediction Model (QPM), which allows calculation of the probability of OMD. Eight hundred three patients were identified (development set, n= 502; validation set, n= 301) with a prevalence of OMD of 9.1%. The developed prediction model included largest mediastinal lymph node size (P< .001), tumor centrality (P= .23), presence of cN1 disease (P= .29), and lesion standardized uptake value (P= .09). Using a calculated probability of more than 10%as a threshold to identify OMD, this model had a sensitivity, specificity, positive predictive value, and negative predictive value in the derivation cohort of 73.9%(95%CI, 58.9%-85.7%), 81.1%(95%CI, 77.2%-84.6%), 28.3%(95%CI, 23.4%-33.8%), and 96.8%(95%CI, 95.0%-98.1%), respectively. It performed similarly in the validation cohort (P = .77, Hosmer-Lemeshow test; P= .5163, Pearson χ2 and unweighted sum-of-squares statistics; and P= .0750, Stukel score test) and outperformed current guideline-recommended criteria in identifying patients with OMD (area under the receiver operating characteristic curve [AUC] for American College of Chest Physicians guidelines criteria, 0.65 [95%CI, 0.59-0.71]; AUC for European Society of Thoracic Surgeons guidelines criteria, 0.60 [95%CI, 0.54-0.67]; and AUC for the QPM, 0.85 [95%CI, 0.80-0.90]). The QPM allows the clinician to integrate available information from CT and PET imaging to minimize invasive staging procedures that will not modify management, while also minimizing the risk of unforeseen mediastinal disease found at surgery.

Evaluation of bone metastasis burden as an imaging biomarker by quantitative single-photon emission computed tomography/computed tomography for assessing prostate cancer with bone metastasis: a phantom and clinical study

Metabolic bone volume (MBV), standardized uptake value (SUV), and total bone uptake (TBU) are new imaging biomarkers for quantitative bone single-photon emission computed tomography/computed tomography. The purpose of this study was to validate the quantitative accuracy and utility of MBV, SUVmean, and TBU for the assessment of bone metastases in prostate cancer. We used a bone-specific phantom with four hot spheres (φ = 13, 17, 22, 28 mm) filled with different Tc-99 m activities to simulate uptake ratios of 3 and 7, corresponding to normal and metastatic values. We calculated the error ratio (%Error) by comparing MBV, SUVmean, and TBU with true values for various parameters, including bone lesion size, uptake ratio, and SUV cut-off level. Differences for MBV, SUVmean, TBU, and bone scan index (BSI) were calculated to verify their utility in assessing bone metastases. Receiver-operating characteristic curve (ROC) analysis was performed to calculate the area under the curve (AUC) for each biomarker. MBV, SUVmean, and TBU were affected by lesion size, uptake ratio, and SUV cut-off level; however, TBU demonstrated the most stable %Error. The TBU %Error was within 15% in spheres 17 mm or larger when the SUV cut-off level was 7, regardless of the uptake ratio. The ROC analyses revealed the AUCs of BSI (0.977) and TBU (0.968). Additionally, TBU was able to assess bone metastasis when BSI provided false-negative results, but TBU also provided false-positive results by degenerative changes. The synergy between TBU and BSI could potentially improve diagnostic accuracy.

18F-FDG-PET/CT Evaluation of Indeterminate Adrenal Masses in Noncancer Patients.

Adrenal tumors in noncancer patients are common. Evaluate performance of 18F-fluorodeoxyglucose positron emission tomography computed tomography (18F-FDG-PET/CT) in distinguishing between benign and malignant adrenal tumors. Retrospective chart review 2010-2019. Academic institution. One hundred and seventeen noncancer patients, defined as having no history of cancer or with cancer in remission for ≥5 years, completed 18F-FDG-PET/CT to evaluate adrenal masses, with pathologic diagnoses or imaging follow-up (≥12 months). 18F-FDG-PET/CT of 117 indeterminate adrenal masses. Receiver operator characteristic curve of the ratios of adrenal lesion standardized uptake value (SUV)max to liver SUVmean and of adrenal lesion SUVmax to aortic arch blood pool SUVmean were constructed. Seventy benign and 47 malignant masses (35 adrenocortical carcinomas [ACCs], 12 adrenal metastases) were identified. Malignant masses had higher median liver SUV and blood pool SUV ratios than benign masses (6.2 and 7.4 vs 1.4 and 2.0, P < .001). Median liver and blood pool SUV ratios of ACC (6.1 and 7.3, respectively) and metastases (6.7 and 7.7, respectively) were higher than those of than adenomas (1.4 and 2.2, P < .05 for all comparisons). Optimal liver SUV ratio to discern between benign and malignant masses was 2.5, yielding 85% sensitivity, 90% specificity, and 7 false negative results (including 3 ACCs). Optimal blood pool SUV ratio was 3.4, yielding 83% sensitivity, 90% specificity, and 8 false negative results (including 4 ACCs). When used in conjunction with other clinical assessments, 18F-FDG-PET/CT can be a valuable tool in evaluating adrenal masses in noncancer patients.

Heterogeneous parameters based on 18F-FET PET imaging can non-invasively predict tumor grade and isocitrate dehydrogenase gene 1 mutation in untreated gliomas.

The present study aimed to explore the efficacy of easily obtained intratumoral heterogeneous parameters, other than regular semi-quantitative parameters, based on static O-(2-[18F]fluoroethyl)-l-tyrosine (18F-FET) positron emission tomography (PET) imaging in glioma grade and isocitrate dehydrogenase (IDH) gene 1 mutation prediction. Fifty-eight adult patients with untreated glioma (grades II-IV) who underwent preoperative 18F-FET PET/computed tomography (CT) imaging were enrolled in the present study. Eight semi-automatically obtained static PET imaging parameters after lesion delineation were chosen for analysis. These were: maximal tumor-to-background ratio (TBRmax), peak tumor-to-background ratio (TBRpeak), mean tumor-to-background ratio (TBRmean), coefficient of variation (COV), heterogeneity index (HI), the standard deviation of lesion standardized uptake value (SUVsd), metabolic tumor volume (MTV), and total lesion tracer standardized uptake (TLU). Pathological and immunohistochemical results were used as a reference. The receiver-operating characteristic analysis was used to investigate the predictive efficacy of these parameters in glioma grade and IDH1 mutation status. TLU [area under the curve (AUC): 0.841, P<0.0001], TBRpeak (AUC: 0.832, P<0.0001), and HI (AUC: 0.826, P<0.0001) had the top 3 single-parameter predictive performance between grade II or III and grade IV glioma patients. Combinations of TBRmax, SUVsd, and TBRmean (AUC: 0.850, P<0.0001); HI, SUVsd, and MTV (AUC: 0.848, P<0.0001); and HI, SUVsd, and TLU (AUC: 0.848, P<0.0001) had the top 3 multiple-parameter predictive performance. SUVsd (AUC: 0.710, P=0.0028), TLU (AUC: 0.698, P=0.0074), and HI (AUC: 0.676, P=0.0159) had the top 3 single-parameter predictive performance in the IDH1 genotype. Combinations of TBRmax, SUVsd, and TBRmean (AUC: 0.821, P<0.0001); SUVsd and TBRmean (AUC: 0.804, P<0.0001); and SUVsd, HI, and TBRmean (AUC: 0.799, P<0.0001) had the top 3 multiple-parameter predictive performance. These easily obtained and highly repetitive heterogeneous parameters based on static 18F-FET PET/CT imaging can non-invasively predict glioma grade and IDH1 mutation, crucial in treatment planning, and prognostic evaluation.

Are lesion features reproducible between 18F-FDG PET/CT images when acquired on analog or digital PET/CT scanners?

To compare lesion features extracted from 18F-FDG PET/CT images acquired on analog and digital scanners, on consecutive imaging data from the same subjects. Whole-body 18F-FDG PET/CT images from 55 oncological patients were acquired twice after a single 18F-FDG injection, with a digital and an analog PET/CT scanner, alternately. Twenty-nine subjects were examined first on the digital, and 26 first on the analog equipment. Image reconstruction was performed using manufacturer standard clinical protocols and protocols that fulfilled EARL1 specifications. Twenty-five features based on lesion standardized uptake value (SUV) and geometry were assessed. To compare these features, intraclass correlation coefficient (ICC), relative difference (RD), absolute value of RD (|RD|), and repeatability coefficient (RC) were used. In total, 323 18F-FDG avid lesions were identified. High agreement (ICC > 0.75) was obtained for most of the lesion features pulled out from both scanners' imaging data, especially when reconstruction protocols fulfilled EARL1 specifications. For EARL1 reconstruction images, the features frequently used in clinics, SUVmax, SUVpeak, SUVmean, metabolic tumor volume, and total lesion glycolysis, reached an ICC of 0.92, 0.95, 0.87, 0.98, and 0.98, and a median RD (digital-analog) of 3%, 5%, 4%, - 3% and 1%, respectively. Using standard reconstruction protocols, the ICC were 0.84, 0.93, 0.80, 0.98, and 0.98, and the RD were 20%, 11%, 13%, - 7%, and 7%, respectively. Under controlled acquisition and reconstruction parameters, most of the features studied can be used for research and clinical work. This is especially important for multicenter studies and patient follow-ups. • Using manufacturer standard clinical reconstruction protocols, lesions SUV was significantly higher when using the digital scanner, especially the SUVmax that was approximately 20% higher. • High agreement was obtained for the majority of the lesion features when using reconstruction protocols that fulfilled EARL1 specifications. • Longitudinal patient studies can be performed interchangeably between digital and analog scanners when both fulfill EARL1 specifications.

Hepatic alveolar echinococcosis: correlation between computed tomography morphology and inflammatory activity in positron emission tomography

Positron emission tomography-computed tomography (PET-CT) with 18F-fluorodesoxyglucose (FDG) is the imaging modality of choice for assessing inflammation surrounding hepatic alveolar echinococcosis (AE) lesions. This study is the first to evaluate FDG uptake in hepatic AE (n = 51) based on the standardized uptake value (SUV) and to correlate the SUVs with primary morphology and calcification patterns, based on the Echinococcus multilocularis Ulm Classification for Computed-Tomography (EMUC-CT). Our results show that the SUVs were increased for lesions with EMUC-CT types I-IV primary morphology, compared to the surrounding healthy liver tissue (SUV = 2.5 ± 0.4; p < 0.05). Type IV lesions included, by far, the highest number of PET-negative lesions. A comparison of lesions with different primary morphologies showed clear differences. The highest SUVs were found for types I and III, and the lowest was found for type IV. Type IV lesions (SUV, 3.8 ± 1.5) showed significantly lower uptake compared to type I (SUV, 6.9 ± 3.5; p = 0.030) and type III (SUV, 7.4 ± 3.9; p = 0.031) lesions. For type II lesions, the results showed only a statistical trend (SUV, 6.1 ± 3.1; p = 0.073). Due to the small number of cases, an evaluation of type V (n = 1) lesions was not possible. The different SUVs of lesions with different primary morphologies, particularly the lower FDG uptake observed in type IV lesions, suggested that these SUVs might reflect different stages of the disease.