Fully automated computational measurement of noise in positron emission tomography.

OBJECTIVES: To introduce an automated computational algorithm that estimates the global noise level across the whole imaging volume of PET datasets. METHODS: [18F]FDG PET images of 38 patients were reconstructed with simulated decreasing acquisition times (15-120 s) resulting in increasing noise levels, and with block sequential regularized expectation maximization with beta values of 450 and 600 (Q.Clear 450 and 600). One reader performed manual volume-of-interest (VOI) based noise measurements in liver and lung parenchyma and two readers graded subjective image quality as sufficient or insufficient. An automated computational noise measurement algorithm was developed and deployed on the whole imaging volume of each reconstruction, delivering a single value representing the global image noise (Global Noise Index, GNI). Manual noise measurement values and subjective image quality gradings were compared with the GNI. RESULTS: Irrespective of the absolute noise values, there was no significant difference between the GNI and manual liver measurements in terms of the distribution of noise values (p = 0.84 for Q.Clear 450, and p = 0.51 for Q.Clear 600). The GNI showed a fair to moderately strong correlation with manual noise measurements in liver parenchyma (r = 0.6 in Q.Clear 450, r = 0.54 in Q.Clear 600, all p < 0.001), and a fair correlation with manual noise measurements in lung parenchyma (r = 0.52 in Q.Clear 450, r = 0.33 in Q.Clear 600, all p < 0.001). Classification performance of the GNI for subjective image quality was AUC 0.898 for Q.Clear 450 and 0.919 for Q.Clear 600. CONCLUSION: An algorithm provides an accurate and meaningful estimation of the global noise level encountered in clinical PET imaging datasets. CLINICAL RELEVANCE STATEMENT: An automated computational approach that measures the global noise level of PET imaging datasets may facilitate quality standardization and benchmarking of clinical PET imaging within and across institutions. KEY POINTS: • Noise is an important quantitative marker that strongly impacts image quality of PET images. • An automated computational noise measurement algorithm provides an accurate and meaningful estimation of the global noise level encountered in clinical PET imaging datasets. • An automated computational approach that measures the global noise level of PET imaging datasets may facilitate quality standardization and benchmarking as well as protocol harmonization.

18F-fluorodeoxyglucose uptake patterns in positron emission tomography/computed tomography caused by inflammation and/or infection after graft surgery for thoracic aortic dissection.

BACKGROUND: To identify 18F-fluorodeoxyglucose (FDG) uptake patterns in positron emission tomography/computed tomography (PET/CT) caused by infection, inflammation, surgical material, and/or graft coating. METHODS AND RESULTS: Of 610 consecutive patients with thoracic aortic graft surgery, 60 patients with 187 PET/CT were retrospectively included. We quantified FDG uptake in all grafts using maximum standardized uptake value (SUVmax) alone and in relation to liver background (SUVratio) and determined the uptake pattern. Mixed linear regression models with random slope and intercept were applied for the analysis of SUVratio over time and generalized estimating equations to analyze the associations with anastomosis uptake. FDG uptake was frequently focal (90%), higher in infected than in noninfected grafts (mean SUVratio 2.19; 95% CI 2.05-2.32 vs. 1.63; 1.46-1.79, P < 0.001), and decreasing slowly over time (SUVratio per year since surgery -0.048; 95% CI -0.15- 0.051, P = 0.34), without a difference in slope between infected and noninfected grafts (P = 0.52). There was no evidence of an interaction between SUVratio and use of BioGlue® surgical adhesive (intercept P = 0.73, slope P = 0.71), or graft coating (gelatin and collagen, all P > 0.7). FDG uptake at the anastomosis was more frequent in noninfected grafts than in infected grafts (66% vs. 21%, odds ratio (OR) 11.34; 95% CI 3.61-35.66, P < 0.001). This effect was attenuated by the use of BioGlue® (OR 5.05; 95% CI 0.45-56.9, P = 0.19). CONCLUSIONS: FDG uptake in PET/CT after thoracic aortic graft surgery is higher in infected grafts than in noninfected grafts. In noninfected grafts, focal uptake is also frequent, mostly anastomosis-associated, not associated with graft coating, and possibly affected by the use of BioGlue®.

International EANM-SNMMI-ISMRM consensus recommendation for PET/MRI in oncology.

PREAMBLE: The Society of Nuclear Medicine and Molecular Imaging (SNMMI) is an international scientific and professional organization founded in 1954 to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM) is a professional non-profit medical association that facilitates communication worldwide between individuals pursuing clinical and research excellence in nuclear medicine. The EANM was founded in 1985. The merged International Society for Magnetic Resonance in Medicine (ISMRM) is an international, nonprofit, scientific association whose purpose is to promote communication, research, development, and applications in the field of magnetic resonance in medicine and biology and other related topics and to develop and provide channels and facilities for continuing education in the field.The ISMRM was founded in 1994 through the merger of the Society of Magnetic Resonance in Medicine and the Society of Magnetic Resonance Imaging. SNMMI, ISMRM, and EANM members are physicians, technologists, and scientists specializing in the research and practice of nuclear medicine and/or magnetic resonance imaging. The SNMMI, ISMRM, and EANM will periodically define new guidelines for nuclear medicine practice to help advance the science of nuclear medicine and/or magnetic resonance imaging and to improve the quality of service to patients throughout the world. Existing practice guidelines will be reviewed for revision or renewal, as appropriate, on their fifth anniversary or sooner, if indicated. Each practice guideline, representing a policy statement by the SNMMI/EANM/ISMRM, has undergone a thorough consensus process in which it has been subjected to extensive review. The SNMMI, ISMRM, and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging and magnetic resonance imaging requires specific training, skills, and techniques, as described in each document. Reproduction or modification of the published practice guideline by those entities not providing these services is not authorized. These guidelines are an educational tool designed to assist practitioners in providing appropriate care for patients. They are not inflexible rules or requirements of practice and are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI, the ISMRM, and the EANM caution against the use of these guidelines in litigation in which the clinical decisions of a practitioner are called into question. The ultimate judgment regarding the propriety of any specific procedure or course of action must be made by the physician or medical physicist in light of all the circumstances presented. Thus, there is no implication that an approach differing from the guidelines, standing alone, is below the standard of care. To the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the guidelines when, in the reasonable judgment of the practitioner, such course of action is indicated by the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the guidelines. The practice of medicine includes both the art and the science of the prevention, diagnosis, alleviation, and treatment of disease. The variety and complexity of human conditions make it impossible to always reach the most appropriate diagnosis or to predict with certainty a particular response to treatment. Therefore, it should be recognized that adherence to these guidelines will not ensure an accurate diagnosis or a successful outcome. All that should be expected is that the practitioner will follow a reasonable course of action based on current knowledge, available resources, and the needs of the patient to deliver effective and safe medical care. The sole purpose of these guidelines is to assist practitioners in achieving this objective.

A third of the radiotracer dose: two decades of progress in pediatric [18F]fluorodeoxyglucose PET/CT and PET/MR imaging.

OBJECTIVES: To assess the evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between years 2000 and 2021. METHODS: Pediatric patients (≤ 16 years) referred for 18F-FDG PET/CT or PET/MR imaging of the body during 2000 and 2021 were retrospectively included. The amount of administered radiotracer activity in megabecquerel (MBq) was recorded, and signal-to-noise ratio (SNR) was measured in the right liver lobe with a 4 cm3 volume of interest as an indicator for objective image quality. Descriptive statistics were computed. RESULTS: Two hundred forty-three children and adolescents underwent a total of 466 examinations. The median injected 18F-FDG activity in MBq decreased significantly from 296 MBq in 2000-2005 to 100 MBq in 2016-2021 (p < 0.001), equaling approximately one-third of the initial amount. The median SNR ratio was stable during all years with 11.7 (interquartile range [IQR] 10.7-12.9, p = 0.133). CONCLUSIONS: Children have benefited from a massive reduction in the administered 18F-FDG dose over the past 20 years without compromising objective image quality. CLINICAL RELEVANCE STATEMENT: Radiotracer dose was reduced considerably over the past two decades of pediatric F-18-fluorodeoxyglucose PET/CT and PET/MR imaging highlighting the success of technical innovations in pediatric PET imaging. KEY POINTS: • The evolution of administered radiotracer activity for F-18-fluorodeoxyglucose (18F-FDG) PET/CT or PET/MR in pediatric patients (0-16 years) between 2000 and 2021 was assessed. • The injected tracer activity decreased by 66% during the study period from 296 megabecquerel (MBq) to 100 MBq (p < 0.001). • The continuous implementation of technical innovations in pediatric hybrid 18F-FDG PET has led to a steady decrease in the amount of applied radiotracer, which is particularly beneficial for children who are more sensitive to radiation.

Expanding the clinicopathological spectrum of TGFBR3-PLAG1 rearranged salivary gland neoplasms with myoepithelial differentiation including evidence of high-grade transformation.

PLAG1 rearrangements have been described as a molecular hallmark of salivary gland pleomorphic adenoma (PA), carcinoma ex pleomorphic adenoma (CEPA), and myoepithelial carcinoma (MECA). Several fusion partners have been described, however, commonly no further assignment to the aforementioned entities or a morphological prediction can be made based on the knowledge of the fusion partner alone. In contrast, TGFBR3-PLAG1 fusion has been specifically described and characterized as an oncogenic driver in MECA, and less common in MECA ex PA. Here, we describe the clinicopathological features of three TGFBR3-PLAG1 fusion-positive salivary gland neoplasms, all of which arose in the deep lobe of the parotid gland. Histopathology showed high morphological similarities, encompassing encapsulation, a polylobular growth pattern, bland basaloid and oncocytoid cells with myoepithelial differentiation, and a distinct sclerotic background. All cases showed at least limited, unusual foci of minimal invasion into adjacent salivary gland tissue, including one case with ERBB2 (Her2/neu) amplified, TP53 mutated high-grade transformation, and lymph node metastases. Of note, all cases illustrated focal ductal differentiation. Classification remains difficult, as morphological overlaps between myoepithelial-rich cellular PA, myoepithelioma, and MECA were observed. However, evidence of minimal invasion advocates classification as low-grade MECA. This case series further characterizes the spectrum of uncommon cellular myoepithelial neoplasms harboring TGFBR3-PLAG1 fusion, which show recurrent minimal invasion of the adjacent salivary gland tissue, a predilection to the deep lobe of the parotid gland, and potential high-grade transformation.

[18F]FDG uptake of axillary lymph nodes after COVID-19 vaccination in oncological PET/CT: frequency, intensity, and potential clinical impact.

OBJECTIVES: To assess the frequency, intensity, and clinical impact of [18F]FDG-avidity of axillary lymph nodes after vaccination with COVID-19 vaccines BNT162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna) in patients referred for oncological FDG PET/CT. METHODS: One hundred forty patients referred for FDG PET/CT during February and March 2021 after first or second vaccination with Pfizer-BioNTech or Moderna were retrospectively included. FDG-avidity of ipsilateral axillary lymph nodes was measured and compared. Assuming no knowledge of prior vaccination, metastatic risk was analyzed by two readers and the clinical impact was evaluated. RESULTS: FDG PET/CT showed FDG-avid lymph nodes ipsilateral to the vaccine injection in 75/140 (54%) patients with a mean SUVmax of 5.1 (range 2.0 - 17.3). FDG-avid lymph nodes were more frequent in patients vaccinated with Moderna than Pfizer-BioNTech (36/50 [72%] vs. 39/90 [43%] cases, p < 0.001). Metastatic risk of unilateral FDG-avid axillary lymph nodes was rated unlikely in 52/140 (37%), potential in 15/140 (11%), and likely in 8/140 (6%) cases. Clinical management was affected in 17/140 (12%) cases. CONCLUSIONS: FDG-avid axillary lymph nodes are common after COVID-19 vaccination. The avidity of lymph nodes is more frequent in Moderna compared to that in Pfizer-BioNTech vaccines. To avoid relatively frequent clinical dilemmas, we recommend carefully taking the history for prior vaccination in patients undergoing FDG PET/CT and administering the vaccine contralateral to primary cancer. KEY POINTS: • PET/CT showed FDG-avid axillary lymph nodes ipsilateral to the vaccine injection site in 54% of 140 oncological patients after COVID-19 vaccination. • FDG-avid lymphadenopathy was observed significantly more frequently in Moderna compared to patients receiving Pfizer-BioNTech-vaccines. • Patients should be screened for prior COVID-19 vaccination before undergoing PET/CT to enable individually tailored recommendations for clinical management.

An essential practice summary of the new EANM guidelines for parathyroid imaging.

Parathyroid imaging is essential for the detection and localization of hyperfunctioning parathyroid tissue in patients with primary hyperparathyroidism (pHPT). Surgical treatment of pHPT mainly consists of minimally invasive parathyroidectomy (MIP), as a single adenoma represents the most common cause of this endocrine disorder. Successful surgery requires an experienced surgeon and relies on the correct preoperative detection and localization of hyperfunctioning parathyroid glands. Failure to preoperatively identify the culprit parathyroid gland by imaging may entail a more invasive surgical approach, including bilateral open neck exploration, with higher morbidity compared to minimally invasive parathyroidectomy. Parathyroid imaging may be also useful before surgery in case of secondary hyperparathyroidism (sHPT) or hereditary disorders (MEN 1, 2, 4) as it enables correct localization of typically located parathyroid glands, detection of ectopic as well as supernumerary glands. It is now accepted by most surgeons experienced in parathyroid surgery that preoperative imaging plays a key role in their patients' management. Recently, the European Association of Nuclear Medicine (EANM) issued an updated version of its Guidelines on parathyroid imaging. Its aim is to precise the role and the advantages and drawbacks of the various imaging modalities proposed or well established in the preoperative imaging strategy. It also aims to favor high performance in indicating, performing, and interpreting those examinations. The objective of the present article is to offer a summary of those recent EANM Guidelines and their originality among other Guidelines in this domain issued by societies of nuclear medicine physicians or other disciplines.

BSREM for Brain Metastasis Detection with 18F-FDG-PET/CT in Lung Cancer Patients.

The aim of the study was to analyze the use of block sequential regularized expectation maximization (BSREM) with different ß-values for the detection of brain metastases in digital fluorine-18 labeled 2-deoxy-2-fluoro-D-glucose (18F-FDG) PET/CT in lung cancer patients. We retrospectively analyzed staging/restaging 18F-FDG PET/CT scans of 40 consecutive lung cancer patients with new brain metastases, confirmed by MRI. PET images were reconstructed using BSREM (ß-values of 100, 200, 300, 400, 500, 600, 700) and OSEM. Two independent blinded readers (R1 and R2) evaluated each reconstruction using a 4-point scale for general image quality, noise, and lesion detectability. SUVmax of metastases, brain background, target-to-background ratio (TBR), and contrast recovery (CR) ratio were recorded for each reconstruction. Among all reconstruction techniques, differences in qualitative parameters were analyzed using non-parametric Friedman test, while differences in quantitative parameters were compared using analysis of variances for repeated measures. Cohen's kappa (k) was used to measure inter-reader agreement. The overall detectability of brain metastases was highest for BSREM200 (R1: 2.83 ± 1.17; R2: 2.68 ± 1.32) and BSREM300 (R1: 2.78 ± 1.23; R2: 2.68 ± 1.36), followed by BSREM100, which had lower accuracy owing to noise. The highest median TBR was found for BSREM100 (R1: 2.19 ± 1.05; R2: 2.42 ± 1.08), followed by BSREM200 and BSREM300. Image quality ratings were significantly different among reconstructions (p < 0.001). The median quality score was higher for BSREM100-300, and both noise and metastases' SUVmax decreased with increasing ß-value. Inter-reader agreement was particularly high for the detectability of photopenic metastases and blurring (all k > 0.65). BSREM200 and BSREM300 yielded the best results for the detection of brain metastases, surpassing both BSREM400 and OSEM, typically used in clinical practice.

The EANM practice guidelines for parathyroid imaging.

INTRODUCTION: Nuclear medicine parathyroid imaging is important in the identification of hyperfunctioning parathyroid glands in primary hyperparathyroidism (pHPT), but it may be also valuable before surgical treatment in secondary hyperparathyroidism (sHPT). Parathyroid radionuclide imaging with scintigraphy or positron emission tomography (PET) is a highly sensitive procedure for the assessment of the presence and number of hyperfunctioning parathyroid glands, located either at typical sites or ectopically. The treatment of pHPT is mostly directed toward minimally invasive parathyroidectomy, especially in cases with a single adenoma. In experienced hands, successful surgery depends mainly on the exact preoperative localization of one or more hyperfunctioning parathyroid adenomas. Failure to preoperatively identify the hyperfunctioning parathyroid gland challenges minimally invasive parathyroidectomy and might require bilateral open neck exploration. METHODS: Over a decade has now passed since the European Association of Nuclear Medicine (EANM) issued the first edition of the guideline on parathyroid imaging, and a number of new insights and techniques have been developed since. The aim of the present document is to provide state-of-the-art guidelines for nuclear medicine physicians performing parathyroid scintigraphy, single-photon emission computed tomography/computed tomography (SPECT/CT), positron emission tomography/computed tomography (PET/CT), and positron emission tomography/magnetic resonance imaging (PET/MRI) in patients with pHPT, as well as in those with sHPT. CONCLUSION: These guidelines are written and authorized by the EANM to promote optimal parathyroid imaging. They will assist nuclear medicine physicians in the detection and correct localization of hyperfunctioning parathyroid lesions.

CT perfusion in peripheral arterial disease-hemodynamic differences before and after revascularisation.

OBJECTIVES: The purpose of this study was the assessment of volumetric CT perfusion (CTP) of the lower leg musculature in patients with symptomatic peripheral arterial disease (PAD) before and after interventional revascularisation. METHODS: Twenty-nine consecutive patients with symptomatic PAD of the lower extremities requiring interventional revascularisation were assessed prospectively. All patients underwent a CTP scan of the lower leg, and hemodynamic and angiographic assessment, before and after intervention. Ankle-brachial pressure index (ABI) was determined. CTP parameters were calculated with a perfusion software, acting on a no outflow assumption. A sequential two-compartment model was used. Differences in CTP parameters were assessed with non-parametric tests. RESULTS: The cohort consisted of 24 subjects with an occlusion, and five with a high-grade stenosis. The mean blood flow before/after (BFpre and BFpost, respectively) was 7.42 ± 2.66 and 10.95 ± 6.64 ml/100 ml*min-1. The mean blood volume before/after (BVpre and BVpost, respectively) was 0.71 ± 0.35 and 1.25 ± 1.07 ml/100 ml. BFpost and BVpost were significantly higher than BFpre and BVpre in the treated limb (p = 0.003 and 0.02, respectively), but not in the untreated limb (p = 0.641 and 0.719, respectively). CONCLUSIONS: CTP seems feasible for assessing hemodynamic differences in calf muscles before and after revascularisation in patients with symptomatic PAD. We could show that CTP parameters BF and BV are significantly increased after revascularisation of the symptomatic limb. In the future, this quantitative method might serve as a non-invasive method for surveillance and therapy control of patients with peripheral arterial disease. KEY POINTS: • CTP imaging of the lower limb in patients with symptomatic PAD seems feasible for assessing hemodynamic differences before and after revascularisation in PAD patients. • This quantitative method might serve as a non-invasive method, for surveillance and therapy control of patients with PAD.

Improved detection of in-transit metastases of malignant melanoma with BSREM reconstruction in digital [18F]FDG PET/CT.

OBJECTIVES: To compare block sequential regularized expectation maximization (BSREM) and ordered subset expectation maximization (OSEM) for the detection of in-transit metastasis (ITM) of malignant melanoma in digital [18F]FDG PET/CT. METHODS: We retrospectively analyzed a cohort of 100 [18F]FDG PET/CT scans of melanoma patients with ITM, performed between May 2017 and January 2020. PET images were reconstructed with both OSEM and BSREM algorithms. SUVmax, target-to-background ratio (TBR), and metabolic tumor volume (MTV) were recorded for each ITM. Differences in PET parameters were analyzed with the Wilcoxon signed-rank test. Differences in image quality for different reconstructions were tested using the Man-Whitney U test. RESULTS: BSREM reconstruction led to the detection of 287 ITM (39% more than OSEM). PET parameters of ITM were significantly different between BSREM and OSEM reconstructions (p < 0.001). SUVmax and TBR were higher (76.5% and 77.7%, respectively) and MTV lower (49.5%) on BSREM. ITM missed with OSEM had significantly lower SUVmax (mean 2.03 vs. 3.84) and TBR (mean 1.18 vs. 2.22) and higher MTV (mean 2.92 vs. 1.01) on OSEM compared to BSREM (all p < 0.001). CONCLUSIONS: BSREM detects significantly more ITM than OSEM, owing to higher SUVmax, higher TBR, and less blurring. BSREM is particularly helpful in small and less avid lesions, which are more often missed with OSEM. KEY POINTS: • In melanoma patients, [18F]FDG PET/CT helps to detect in-transit metastases (ITM), and their detection is improved by using BSREM instead of OSEM reconstruction. • BSREM is particularly useful in small lesions.

Role of intravoxel incoherent motion parameters in gastroesophageal cancer: relationship with 18F-FDG-positron emission tomography, computed tomography perfusion and magnetic resonance perfusion imaging parameters.

BACKGROUND: Identification of pretherapeutic predictive markers in gastro-esophageal cancer is essential for individual-oriented treatment. This study evaluated the relationship of multimodality parameters derived from intravoxel incoherent motion method (IVIM), 18F-FDG-positron emission tomography (PET), computed tomography (CT) perfusion and dynamic contrast enhanced magnetic resonance imaging (MRI) in patients with gastro-esophageal cancer and investigated their histopathological correlation. METHODS: Thirty-one consecutive patients (28 males; median age 63.9 years; range 37-84 years) with gastro-esophageal adenocarcinoma (N.=22) and esophageal squamous cell carcinoma (N.=9) were analyzed. IVIM parameters: pseudodiffusion (D*), perfusion fraction (fp), true diffusion (D) and the threshold b-value (bval); PET-parameters: SUVmax, metabolic tumor volume (MTV) and total lesion glycolysis (TLG); CT perfusion parameters: blood flow (BF), blood volume (BV) and mean transit time (MTT); and MR perfusion parameters: time to enhance, positive enhancement integral, time-to-peak (TTP), maximum-slope-of-increase, and maximum-slope-of-decrease were determined, and correlated to each other and to histopathology. RESULTS: IVIM and PET parameters showed significant negative correlations: MTV and bval (rs =-0.643, P=0.002), TLG and bval (rs=-0.699, P<0.01) and TLG and fp (rs=-0.577, P=0.006). Positive correlation was found for TLG and D (rs=0.705, P=0.000). Negative correlation was found for bval and staging (rs=0.590, P=0.005). Positive correlation was found for positive enhancement interval and BV (rs=0.547, P=0.007), BF and regression index (rs=0.753, P=0.005) and for time-to-peak and staging (rs=0.557, P=0.005). CONCLUSIONS: IVIM parameters (bval, fp, D) provide quantitative information and correlate with PET parameters (MTV, TLG) and staging. IVIM might be a useful tool for additional characterization of gastro-esophageal cancer.

The Future of Cancer Diagnosis, Treatment and Surveillance: A Systemic Review on Immunotherapy and Immuno-PET Radiotracers.

Immunotherapy is an effective therapeutic option for several cancers. In the last years, the introduction of checkpoint inhibitors (ICIs) has shifted the therapeutic landscape in oncology and improved patient prognosis in a variety of neoplastic diseases. However, to date, the selection of the best patients eligible for these therapies, as well as the response assessment is still challenging. Patients are mainly stratified using an immunohistochemical analysis of the expression of antigens on biopsy specimens, such as PD-L1 and PD-1, on tumor cells, on peritumoral immune cells and/or in the tumor microenvironment (TME). Recently, the use and development of imaging biomarkers able to assess in-vivo cancer-related processes are becoming more important. Today, positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is used routinely to evaluate tumor metabolism, and also to predict and monitor response to immunotherapy. Although highly sensitive, FDG-PET in general is rather unspecific. Novel radiopharmaceuticals (immuno-PET radiotracers), able to identify specific immune system targets, are under investigation in pre-clinical and clinical settings to better highlight all the mechanisms involved in immunotherapy. In this review, we will provide an overview of the main new immuno-PET radiotracers in development. We will also review the main players (immune cells, tumor cells and molecular targets) involved in immunotherapy. Furthermore, we report current applications and the evidence of using [18F]FDG PET in immunotherapy, including the use of artificial intelligence (AI).

Artificial intelligence for detecting small FDG-positive lung nodules in digital PET/CT: impact of image reconstructions on diagnostic performance.

OBJECTIVES: To evaluate the diagnostic performance of a deep learning algorithm for automated detection of small 18F-FDG-avid pulmonary nodules in PET scans, and to assess whether novel block sequential regularized expectation maximization (BSREM) reconstruction affects detection accuracy as compared to ordered subset expectation maximization (OSEM) reconstruction. METHODS: Fifty-seven patients with 92 18F-FDG-avid pulmonary nodules (all ≤ 2 cm) undergoing PET/CT for oncological (re-)staging were retrospectively included and a total of 8824 PET images of the lungs were extracted using OSEM and BSREM reconstruction. Per-slice and per-nodule sensitivity of a deep learning algorithm was assessed, with an expert readout by a radiologist/nuclear medicine physician serving as standard of reference. Receiver-operator characteristic (ROC) curve of OSEM and BSREM were assessed and the areas under the ROC curve (AUC) were compared. A maximum standardized uptake value (SUVmax)-based sensitivity analysis and a size-based sensitivity analysis with subgroups defined by nodule size was performed. RESULTS: The AUC of the deep learning algorithm for nodule detection using OSEM reconstruction was 0.796 (CI 95%; 0.772-0.869), and 0.848 (CI 95%; 0.828-0.869) using BSREM reconstruction. The AUC was significantly higher for BSREM compared to OSEM (p = 0.001). On a per-slice analysis, sensitivity and specificity were 66.7% and 79.0% for OSEM, and 69.2% and 84.5% for BSREM. On a per-nodule analysis, the overall sensitivity of OSEM was 81.5% compared to 87.0% for BSREM. CONCLUSIONS: Our results suggest that machine learning algorithms may aid detection of small 18F-FDG-avid pulmonary nodules in clinical PET/CT. AI performed significantly better on images with BSREM than OSEM. KEY POINTS: • The diagnostic value of deep learning for detecting small lung nodules (≤ 2 cm) in PET images using BSREM and OSEM reconstruction was assessed. • BSREM yields higher SUVmaxof small pulmonary nodules as compared to OSEM reconstruction. • The use of BSREM translates into a higher detectability of small pulmonary nodules in PET images as assessed with artificial intelligence.

Diagnostic Accuracy of PET/CT and Contrast Enhanced CT in Patients With Suspected Infected Aortic Aneurysms.

OBJECTIVE: Infected aortic aneurysms are highly lethal, and management is very demanding, requiring an early diagnosis. The aim of this study was to evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT) and contrast enhanced CT (CE-CT) in patients with suspected infected aortic aneurysms. METHODS: PET/CT was performed in patients with clinically suspected infected aortic aneurysms, and additional CE-CT was performed if feasible. Diagnostic accuracy was assessed by two independent readers using a four point grading score for both imaging modalities. Maximum standardised uptake values (SUVmax) were calculated for quantitative measurements of metabolic activity in PET/CT. The reference standard was a combination of clinical presentation, laboratory findings, and imaging. RESULTS: Ten patients were included prospectively in the study, 24 retrospectively; 16 patients (47%) prior to the start of antimicrobial treatment and all 34 patients prior to any vascular intervention. Thirteen of the 34 patients had an infected aortic aneurysm (38%). Proven infected aortic aneurysms were all metabolically active on PET/CT with a median SUVmax of 6.6 (interquartile range 4.7-21.8). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of PET/CT for the diagnosis of infected aortic aneurysm was 100%, 71%, 68%, 100%, and 82%, for reader 1 and 85%, 71%, 65%, 88%, and 77%, for reader 2. Respective values for CE-CT, performed in 20 patients (59%), were 63%, 75%, 63%, 75%, and 70%, for reader 1 and 88%, 50%, 54%, 86%, and 65%, for reader 2. CONCLUSION: The diagnostic accuracy of PET/CT in the detection of infected aortic aneurysms (n = 13) is high, and higher than CE-CT. While PET/CT demonstrates an excellent sensitivity, its specificity is hampered because of false positive findings.

Prognostic value of O-(2-[18F]-fluoroethyl)-L-tyrosine PET in relapsing oligodendroglioma.

PURPOSE: To assess the relationship between F-18-fluoro-ethyl-tyrosine positron emission tomography (FET-PET) parameters of relapsing oligodendroglioma and progression-free survival. MATERIAL AND METHODS: The relationship of clinical parameters, FET-PET parameters (SUVmax, TBRmax, BTV, time-activity curves) and progression-free survival was analyzed using univariate and multivariate analysis in 42 adult patients with relapsing oligodendroglioma. Kaplan-Meier analysis was used to assess survival. RESULTS: Patients who did not undergo surgical resection of their relapsing tumor had significantly lower PFS if the tumor exhibited an SUVmax above 3.40 than those with an SUVmax below 3.40 (13.1 ± 2.3 months vs. 47.3 ± 6.0 months, respectively, p < .001). Patients who underwent surgery had similar PFS as the aforementioned non-operated patients with low SUVmax (53.6 ± 6.7 months, p = .948). The same was true for TBRmax using a threshold of 3.03 (PFS 12.5 ± 2.4 months vs. 44.0 ± 6.3 months / 53.6 ± 6.7 months, respectively; p < .001 / p = .825). Also, subjects with BTV below 10 cm3 that did not undergo surgery had a similar PFS as subjects who underwent surgery (40.2 ± 6.0 months vs. 52.4 ± 8.9 months, respectively, p = .587). Subjects with BTV above 10 cm3 and without surgery had a significantly worse PFS (13.8 ± 3.3 months, p < .001). Multivariate analysis showed that the prognostication by clinical parameters is improved by adding TBRmax to the model (AUC 0.945 (95% CI: 0.881-1.000), true classification rate 88.1%). CONCLUSION: FET-PET may provide added value for the prognostication of relapsing oligodendroglioma in addition to clinical parameters.

Comparing diagnostic accuracy of 18F-FDG-PET/CT, contrast enhanced CT and combined imaging in patients with suspected vascular graft infections.

BACKGROUND: To evaluate the diagnostic accuracy of positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (PET/CT), contrast-enhanced CT (CE-CT), and a combined imaging approach (CE-PET/CT) in patients with suspected vascular graft infection (VGI). METHODS: PET/CT and CE-CT were performed prospectively in 23 patients with suspected VGI. Diagnostic accuracy for PET/CT was assessed by using previously suggested cut-off points for maximum standardized uptake values (SUVmax) measured in the vicinity of the graft. Using a new 4-point scale for visual grading, two readers independently assessed the diagnostic accuracy for CE-CT and combined CE-PET/CT. Microbiological culture, obtained after open biopsy or graft explantation, and clinical follow-up of the patients served as the standard of reference. RESULTS: Sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and accuracy of PET/CT for the diagnosis of VGI was 100%, 50%, 100%, 72.2%, and 78.3%, using the most favorable SUVmax cut-off ≥ 4.9. Respective values for CE-CT were 100%, 50%, 100%, 72.2%, and 78.3% for reader 1, and 92.3%, 80%, 88.9%, 85.7%, and 86.9% for reader 2; while respective values for combined CE-PET/CT were 100%, 70%, 100%, 81.3%, and 86.9% for reader 1, and 100%, 80%, 100%, 86.7%, and 91.3% for reader 2. Additionally, imaging provided a conclusive clinical diagnosis in patients without graft infection (i.e., other sites of infection): five of ten patients with CE-CT, six of ten patients with PET/CT, and seven of ten patients with combined CE-PET/CT. CONCLUSION: The diagnostic accuracy of combined CE-PET/CT in patients with suspected VGI is very high. The combination of the high sensitivity of PET/CT in detecting metabolically active foci in infection, and the high specificity of CE-CT in detecting anatomic alterations, appears to be the reason why combined imaging outperforms stand-alone imaging in diagnosing VGI and may be supportive in future decision-making of difficult cases of suspected VGI. Clinical Trials.gov Identifier: NCT01821664.

CT radiomics and PET radiomics: ready for clinical implementation?

INTRODUCTION: Today, rapid technical and clinical developments result in an increasing number of treatment options for oncological diseases. Thus, decision support systems are needed to offer the right treatment to the right patient. Imaging biomarkers hold great promise in patient-individual treatment guidance. Routinely performed for diagnosis and staging, imaging datasets are expected to hold more information than used in the clinical practice. Radiomics describes the extraction of a large number of meaningful quantitative features from medical images, such as computed tomography (CT) and positron emission tomography (PET). Due to the non-invasive nature and ability to capture 3D image-based heterogeneity, radiomic features are potential surrogate markers of the cancer phenotype. Several radiomic studies are published per day, owing to encouraging results of many radiomics-based patient outcome models. Despite this comparably large number of studies, radiomics is mainly studied in proof of principle concept. Hence, a translation of radiomics from a hot topic research field into an essential clinical decision-making tool is lacking, but of high clinical interest. EVIDENCE ACQUISITION: Herein, we present a literature review addressing the clinical evidence of CT and PET radiomics. An extensive literature review was conducted in PubMed, including papers on robustness and clinical applications. EVIDENCE SYNTHESIS: We summarize image-modality related influences on the robustness of radiomic features and provide an overview of clinical evidence reported in the literature. Today, more evidence has been provided for CT imaging, however, PET imaging offers the promise of direct imaging of biological processes and functions. We provide a summary of future research directions, which needs to be addressed in order to successfully introduce radiomics into clinical medicine. In comparison to CT, more focus should be directed towards harmonization of PET acquisition and reconstruction protocols, which is important for transferable modelling. CONCLUSIONS: Both CT and PET radiomics are promising pre-treatment and intra-treatment biomarkers for outcome prediction. Most studies are performed in retrospective setting, however their validation in prospective data collections is ongoing.