Towards Understanding the Survival of Patients with High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms: An Investigation of Ensemble Feature Selection in the Prediction of Overall Survival

Determining the most informative features for predicting the overall survival of patients diagnosed with high-grade gastroenteropancreatic neuroendocrine neoplasms is crucial to improve individual treatment plans for patients, as well as the biological understanding of the disease. Recently developed ensemble feature selectors like the Repeated Elastic Net Technique for Feature Selection (RENT) and the User-Guided Bayesian Framework for Feature Selection (UBayFS) allow the user to identify such features in datasets with low sample sizes. While RENT is purely data-driven, UBayFS is capable of integrating expert knowledge a priori in the feature selection process. In this work we compare both feature selectors on a dataset comprising of 63 patients and 134 features from multiple sources, including basic patient characteristics, baseline blood values, tumor histology, imaging, and treatment information. Our experiments involve data-driven and expert-driven setups, as well as combinations of both. We use findings from clinical literature as a source of expert knowledge. Our results demonstrate that both feature selectors allow accurate predictions, and that expert knowledge has a stabilizing effect on the feature set, while the impact on predictive performance is limited. The features WHO Performance Status, Albumin, Platelets, Ki-67, Tumor Morphology, Total MTV, Total TLG, and SUVmax are the most stable and predictive features in our study.submittedVersio

Inter-reader agreement of 18F-FDG PET/CT for the quantification of carotid artery plaque inflammation

Introduction A significant proportion of ischemic strokes are caused by emboli from unstable atherosclerotic carotid artery plaques. Inflammation is a key feature of plaque instability. Positron emission tomography/computed tomography (PET/CT) with 2-deoxy-2-( 18 F)-fluoro-D-glucose ( 18 F-FDG) is a promising technique to quantify plaque inflammation, but a consensus on the methodology has not been established. High inter-reader agreement is essential if 18 F-FDG PET/CT is to be used as a clinical tool for the assessment of unstable plaques and stroke risk. Methods We assessed the inter-reader variability of different methods for quantification of 18 F-FDG uptake in 43 patients with carotid artery stenosis ≥70%. Two independent readers delineated the plaque and collected maximum standardized uptake value (SUV max ) from all axial PET slices containing the atherosclerotic plaque. Results Uptake values with and without background correction were calculated and intraclass correlation coefficients were highest for uncorrected uptake values (0.97–0.98) followed by those background corrected by subtraction (0.89–0.94) and lowest for those background corrected by division (0.74–0.79). Conclusion Quantification methods without background correction have the highest inter-reader agreement for 18 F-FDG PET of carotid artery plaque inflammation. The use of the single highest uptake value (max SUV max ) from the plaque will facilitate the method’s clinical utility in stroke prevention

The utility of PET imaging in the diagnosis and management of psychosis: a brief review

Abstract Purpose Advances in the pathophysiological characterization of psychosis has led to a newfound role of biomarkers in diagnostic and prognostic contexts. Further, advances in the accuracy and sensitivity of nuclear medicine imaging techniques, and specifically positron emission tomography (PET), have improved the ability to diagnose and manage individuals experiencing first-episode psychosis or those at greater risk for developing psychosis. Methods Literature searches were performed in PubMed, Google Scholar, and Web of Science to identify papers related to the use of PET imaging in the diagnosis or management of psychosis. Search terms used included “positron emission tomography”, “PET imaging”, “psychosis”, “disorders of psychosis”, “schizophrenia”, “biomarkers”, “diagnostic biomarkers”, “prognostic biomarker”, “monitoring biomarker”, “outcome biomarker”, and “predictive biomarker.” Results Studies included fell into three categories: those examining microglia, those studying dopamine synthesis capacity, and those examining acetylcholine receptor activity. Microglial imaging has been shown to be ineffective in all patients with psychosis, but some believe it shows promise in a subset of patients with psychosis, although no defining characteristics of said subset have been postulated. Studies of dopamine synthesis capacity suggest that presynaptic dopamine is reliably elevated in patients with psychosis, but levels of dopamine active transporter are not. Further, positron emission tomography (PET) with [18F]fluoro- l -dihydroxyphenylalanine ([ 18 F]FDOPA)-PET has been recently used successfully as a predictive biomarker of dopaminergic treatment response, although more work is needed to validate such findings. Finally, existing studies have also documented lower levels of binding to the α7 nicotinic cholinergic receptor (α7-nAChR) via [ 18 F]-ASEM PET in patients with psychosis, however there is a dearth of prospective, randomized studies evaluating the efficacy of [ 18 F]-ASEM as a diagnostic or monitoring biomarker of any kind. Conclusion Molecular imaging has become a useful tool in the diagnosis and management of psychosis. Further work must be done to improve the comparative prognostic value and diagnostic accuracy of different radiotracers

Optimization of Q.Clear reconstruction for dynamic 18F PET imaging

Abstract Background Q.Clear, a Bayesian penalized likelihood reconstruction algorithm, has shown high potential in improving quantitation accuracy in PET systems. The Q.Clear algorithm controls noise during the iterative reconstruction through a β penalization factor. This study aimed to determine the optimal β-factor for accurate quantitation of dynamic PET scans. Methods A Flangeless Esser PET Phantom with eight hollow spheres (4–25 mm) was scanned on a GE Discovery MI PET/CT system. Data were reconstructed into five sets of variable acquisition times using Q.Clear with 18 different β-factors ranging from 100 to 3500. The recovery coefficient (RC), coefficient of variation (CVRC) and root-mean-square error (RMSERC) were evaluated for the phantom data. Two male patients with recurrent glioblastoma were scanned on the same scanner using 18F-PSMA-1007. Using an irreversible two-tissue compartment model, the area under curve (AUC) and the net influx rate Ki were calculated to assess the impact of different β-factors on the pharmacokinetic analysis of clinical PET brain data. Results In general, RC and CVRC decreased with increasing β-factor in the phantom data. For small spheres (< 10 mm), and in particular for short acquisition times, low β-factors resulted in high variability and an overestimation of measured activity. Increasing the β-factor improves the variability, however at a cost of underestimating the measured activity. For the clinical data, AUC decreased and Ki increased with increased β-factor; a change in β-factor from 300 to 1000 resulted in a 25.5% increase in the Ki. Conclusion In a complex dynamic dataset with variable acquisition times, the optimal β-factor provides a balance between accuracy and precision. Based on our results, we suggest a β-factor of 300–500 for quantitation of small structures with dynamic PET imaging, while large structures may benefit from higher β-factors. Trial registration Clinicaltrials.gov, NCT03951142. Registered 5 October 2019, https://clinicaltrials.gov/ct2/show/NCT03951142 . EudraCT no 2018-003229-27. Registered 26 February 2019, https://www.clinicaltrialsregister.eu/ctr-search/trial/2018-003229-27/NO

Critical review of PET imaging for detection and characterization of the atherosclerotic plaques with emphasis on limitations of FDG-PET compared to NaF-PET in this setting

Applications of various positron emission tomography (PET) tracers for assessing atherosclerosis have been evolving over the years. 18F-fluorodeoxyglucose (FDG)-PET was introduced in 2001 as a probe for this purpose. During the past decade, numerous papers have described a major role for sodium 18F-fluoride (NaF) as another tracer for assessing this vascular disease. We have reviewed the existing data about the merits of both techniques for assessing atherosclerosis. We have to emphasize that our team has been actively involved in conducting research with both tracers over many years. In this review, we have relied upon the data from the CAMONA study which has become a gold standard for defining the role of PET imaging in atherosclerosis. This study was one of the largest of any in recent years and has allowed comprehensive comparison between these two tracers in detecting and quantifying atherosclerosis. Based on what we have learned from this major undertaking, we believe the role of FDG-PET will be limited in assessing atherosclerosis in clinical work-up. This is relevant to both major and coronary arteries. In contrast to NaF-PET, the role of FDG-PET in assessing coronary artery atherosclerosis is almost non-existent. Based on the existing data in this domain, NaF-PET is an ideal imaging modality for both research and clinical assessment of atherosclerosis. The aim of this review is to describe the pros and cons of both approaches based on the existing data in the literature

Multimodal functional imaging for early response assessment in patients with gastrointestinal stromal tumor treated with tyrosine kinase inhibitors

Background: Several imaging modalities are used in the early work-up of patients with gastrointestinal stromal tumor (GIST) receiving tyrosine kinase inhibitor (TKI) treatment and there is a need to establish whether they provide similar or complimentary information. Purpose: To compare 18F-fluorodeoxyglucose positron emission tomography (FDG PET), computed tomography (CT) and magnetic resonance imaging (MRI) as early predictors of three-month outcomes for patients with GIST receiving TKI treatment. Material and methods: Thirty-five patients with advanced GIST were prospectively included between February 2011 and June 2017. FDG PET, contrast-enhanced CT (CECT), and MRI were performed before and early after onset of TKI treatment (range 8-18 days). Early response was categorized according to mRECIST (CT), the Choi criteria (CECT), and PERCIST (FDG PET/CT). For MRI, volumetry from T2-weighted images and change in apparent diffusion coefficient (ADC) from diffusion-weighted imaging was used. The reference standard for early assessment was the three-month mRECIST evaluation based on CT. At three months, both stable disease (SD) and partial response (PR) were categorized as response. Clinical usefulness was defined as agreement between early and three-month assessment. Results: At the three-month assessment, 91% (32/35) were responders, 37% (13/35) PR, 54% (19/35) SD, and 9% (3/35) had progressive disease (PD). Early assessment correctly predicted three-month response in 93% (27/29) for MRI, 80% (28/35) for PERCIST, 74% (26/35) for Choi, and 23% (8/35) for mRECIST. Six patients had non-FDG-avid tumors. For the FDG-avid tumors, PET/CT correctly predicted three-month response in 97% (28/29). Conclusion: MRI was superior to CECT for early assessment of TKI-treatment response in GIST. If the tumor was FDG-avid, PET and MRI were equally good. Changes in functional parameters were superior to changes in longest tumor diameter (mRECIST)

Non-18F-FDG/18F-NaF radiotracers proposed for the diagnosis and management of diseases of the heart and vasculature

18F-FDG and 18F-NaF have been used extensively in the identification of various cardiovascular diseases, but not without limitations. Several other PET radiotracers have been identified as possible markers for cardiovascular-associated inflammation and infection. Non-18F-FDG/18F-NaF molecules may have utility as alternative radiotracers in the detection and management of cardiovascular diseases, but few have demonstrated clinical value

FDG PET/CT parameters and correlations with tumor-absorbed doses in a phase 1 trial of 177Lu-lilotomab satetraxetan for treatment of relapsed non-Hodgkin lymphoma

Purpose 177Lu-lilotomab satetraxetan targets the CD37 antigen and has been investigated in a first-in-human phase 1/2a study for relapsed non-Hodgkin lymphoma (NHL). Tumor dosimetry and response evaluation can be challenging after radioimmunotherapy (RIT). Changes in FDG PET/CT parameters after RIT and correlations with tumor-absorbed doses has not been examined previously in patients with lymphoma. Treatment-induced changes were measured at FDG PET/CT and ceCT to evaluate response at the lesion level after treatment, and correlations with tumor-absorbed doses were investigated. Methods Forty-five tumors in 16 patients, with different pre-treatment and pre-dosing regimens, were included. Dosimetry was performed based on multiple SPECT/CT images. FDG PET/CT was performed at baseline and at 3 and 6 months. SUVmax, MTV, TLG, and changes in these parameters were calculated for each tumor. Lesion response was evaluated at 3 and 6 months (PET3months and PET6months) based on Deauville criteria. Anatomical changes based on ceCT at baseline and at 6 and 12 months were investigated by the sum of perpendiculars (SPD). Results Tumor-absorbed doses ranged from 35 to 859 cGy. Intra- and interpatient variations were observed. Mean decreases in PET parameters from baseline to 3 months were ΔSUVmax-3months 61%, ΔMTV3months 80%, and ΔTLG3months 77%. There was no overall correlation between tumor-absorbed dose and change in FDG PET or ceCT parameters at the lesion level or significant difference in tumor-absorbed doses between metabolic responders and non-responders after treatment. Conclusion Our analysis does not show any correlation between tumor-absorbed doses and changes in FDG PET or ceCT parameters for the included lesions. The combination regimen, including cold antibodies, may be one of the factors precluding such a correlation. Increased intra-patient response with increased tumor-absorbed doses was observed for most patients, implying individual variations in radiation sensitivity or biology

Tau Imaging in Head Injury

Key points Misfolded tau proteins underlie chronic traumatic encephalopathy (CTE) related to head trauma. Tau-PET radiotracers have shown superior specificity and selectivity. Tau-PET imaging of head trauma populations has shown elevated tau uptake related to CTE

Evaluation of semi-quantitative measures of 18F-Flutemetamol PET for the clinical diagnosis of Alzheimer’s disease

Background: 18F-flutemetamol positron emission tomography (PET) is used to assess cortical amyloid-β burden in patients with cognitive impairment to support a clinical diagnosis. Visual classification is the most widely used method in clinical practice although semi-quantification is beneficial to obtain an objective and continuous measure of the Aβ burden. The aims were: first to evaluate the correspondence between standardized uptake value ratios (SUVRs) from three different software, Centiloids and visual classification, second to estimate thresholds for supporting visual classification and last to assess differences in semi-quantitative measures between clinical diagnoses. Methods: This observational study included 195 patients with cognitive impairment who underwent 18F-flutemetamol PET. PET images were semi-quantified with SyngoVia, CortexID suite, and PMOD. Receiver operating characteristics curves were used to compare visual classification with composite SUVR normalized to pons (SUVRpons) and cerebellar cortex (SUVRcer), and Centiloids. We explored correlations and differences between semi-quantitative measures as well as differences in SUVR between two clinical diagnosis groups: Alzheimer’s disease-group and non-Alzheimer’s disease-group. Results: PET images from 191 patients were semi-quantified with SyngoVia and CortexID and 86 PET-magnetic resonance imaging pairs with PMOD. All receiver operating characteristics curves showed a high area under the curve (>0.98). Thresholds for a visually positive PET was for SUVRcer: 1.87 (SyngoVia) and 1.64 (CortexID) and for SUVRpons: 0.54 (SyngoVia) and 0.55 (CortexID). The threshold on the Centiloid scale was 39.6 Centiloids. All semi-quantitative measures showed a very high correlation between different software and normalization methods. Composite SUVRcer was significantly different between SyngoVia and PMOD, SyngoVia and CortexID but not between PMOD and CortexID. Composite SUVRpons were significantly different between all three software. There were significant differences in the mean rank of SUVRpons, SUVRcer, and Centiloid between Alzheimer’s disease-group and non-Alzheimer’s disease-group. Conclusions: SUVR from different software performed equally well in discriminating visually positive and negative 18F-Flutemetamol PET images. Thresholds should be considered software-specific and cautiously be applied across software without preceding validation to categorize scans as positive or negative. SUVR and Centiloid may be used alongside a thorough clinical evaluation to support a clinical diagnosis