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Background: Programmed death-ligand 1 (PD-L1) expression is a predictive biomarker for immunotherapy in non-small cell lung cancer (NSCLC). PD-L1 and glucose transporter 1 expression are closely associated, and studies demonstrate correlation of PD-L1 with glucose metabolism., Aim: The aim of this study was to investigate the association of fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) metabolic parameters with PD-L1 expression in primary lung tumour and lymph node metastases in resected NSCLC., Methods: We conducted a retrospective analysis of 210 patients with node-positive resectable stage IIB-IIIB NSCLC. PD-L1 tumour proportion score (TPS) was determined using the DAKO 22C3 immunohistochemical assay. Semi-automated techniques were used to analyse pre-operative [ 18 F]FDG-PET/CT images to determine primary and nodal metabolic parameter scores (including max, mean, peak and peak adjusted for lean body mass standardised uptake values (SUV), metabolic tumour volume (MTV), total lesional glycolysis (TLG) and SUV heterogeneity index (HISUV))., Results: Patients were predominantly male (57%), median age 70 years with non-squamous NSCLC (68%). A majority had negative primary tumour PD-L1 (TPS < 1%; 53%). Mean SUV max , SUV mean , SUV peak and SUL peak values were significantly higher (p < 0.05) in those with TPS ≥ 1% in primary tumour (n = 210) or lymph nodes (n = 91). However, ROC analysis demonstrated only moderate separability at the 1% PD-L1 TPS threshold (AUCs 0.58-0.73). There was no association of MTV, TLG and HISUV with PD-L1 TPS., Conclusion: This study demonstrated the association of SUV-based [ 18 F]FDG-PET/CT metabolic parameters with PD-L1 expression in primary tumour or lymph node metastasis in resectable NSCLC, but with poor sensitivity and specificity for predicting PD-L1 positivity ≥ 1%., Clinical Relevance Statement: Whilst SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography metabolic parameters may not predict programmed death-ligand 1 positivity ≥ 1% in the primary tumour and lymph nodes of resectable non-small cell lung cancer independently, there is a clear association which warrants further investigation in prospective studies., Trial Registration: Non-applicable KEY POINTS: • Programmed death-ligand 1 immunohistochemistry has a predictive role in non-small cell lung cancer immunotherapy; however, it is both heterogenous and dynamic. • SUV-based fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) metabolic parameters were significantly higher in primary tumour or lymph node metastases with positive programmed death-ligand 1 expression. • These SUV-based parameters could potentially play an additive role along with other multi-modal biomarkers in selecting patients within a predictive nomogram., (© 2024. The Author(s).)

Purpose: Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma., Methods: Forty-six patients undergoing 18F-FDG PET/CT and WBMRI were reviewed by a nuclear medicine physician and radiologist, respectively, for the presence of myeloma bone disease. Blinded clinical and imaging data were reviewed by two haematologists in consensus and management recorded following clinical data ± 18F-FDG PET/CT or WBMRI. Bone disease was defined using International Myeloma Working Group (IMWG) criteria and a clinical reference standard. Per-patient sensitivity for lesion detection was established. McNemar test compared management based on clinical assessment ± 18F-FDG PET/CT or WBMRI., Results: Sensitivity for bone lesions was 69.6% (32/46) for 18F-FDG PET/CT (54.3% (25/46) for PET component alone) and 91.3% (42/46) for WBMRI. 27/46 (58.7%) of cases were concordant. In 19/46 patients (41.3%) WBMRI detected more focal bone lesions than 18F-FDG PET/CT. Based on clinical data alone, 32/46 (69.6%) patients would have been treated. Addition of 18F-FDG PET/CT to clinical data increased this to 40/46 (87.0%) patients (p = 0.02); and WBMRI to clinical data to 43/46 (93.5%) patients (p = 0.002). The difference in treatment decisions was not statistically significant between 18F-FDG PET/CT and WBMRI (p = 0.08)., Conclusion: Compared to 18F-FDG PET/CT, WBMRI had a higher per patient sensitivity for bone disease. However, treatment decisions were not statistically different and either modality would be appropriate in initial staging, depending on local availability and expertise.

Radiomics describes the extraction of multiple features from medical images, including molecular imaging modalities, that with bioinformatic approaches, provide additional clinically relevant information that may be invisible to the human eye. This information may complement standard radiological interpretation with data that may better characterize a disease or that may provide predictive or prognostic information. Progressing from predefined image features, often describing heterogeneity of voxel intensities within a volume of interest, there is increasing use of machine learning to classify disease characteristics and deep learning methods based on artificial neural networks that can learn features without a priori definition and without the need for preprocessing of images. There have been advances in standardization and harmonization of methods to a level that should support multicenter studies. However, in this relatively early phase of research in the field, there are limited aspects that have been adopted into routine practice. Most of the reports in the molecular imaging field describe radiomic approaches in cancer using 18 F-fluorodeoxyglucose positron emission tomography ( 18 F-FDG-PET). In this review, we will describe radiomics in molecular imaging and summarize the pertinent literature in lung cancer where reports are most prevalent and mature., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: Treatment of metastatic colorectal cancer frequently includes antiangiogenic agents such as bevacizumab. Size measurements are inadequate to assess treatment response to these agents, and newer response assessment criteria are needed. We aimed to evaluate F-FDG PET-derived texture parameters in a preclinical colorectal cancer model as alternative metrics of response to treatment with bevacizumab., Materials and Methods: Fourteen CD1 athymic mice injected in the flank with 5×106 LS174T cells (human colorectal carcinoma) were either untreated controls (n=7) or bevacizumab treated (n=7). After 2 weeks, mice underwent F-FDG PET/CT. Calliper-measured tumor growth (Δvol) and final tumor volume (Volcal), F-FDG PET metabolically active volume (Volmet), mean metabolism (Metmean), and maximum metabolism (Metmax) were measured. Twenty-four texture features were compared between treated and untreated mice. Immunohistochemical mean tumor vascular density was estimated by anti-CD-34 staining after tumor resection., Results: Treated mice had significantly lower tumor vascular density (P=0.032), confirming the antiangiogenic therapeutic effect of bevacizumab. None of the conventional measures were different between the two groups: Δvol (P=0.9), Volcal (P=0.7), Volmet (P=0.28), Metmax (P=0.7), or Metmean (P=0.32). One texture parameter, GLSZM-SZV (visually indicating that the F-FDG PET images of treated mice comprise uniformly sized clusters of different activity) had significantly different means between the two groups of mice (P=0.001)., Conclusion: F-FDG PET derived texture parameters, particularly GLSZM-SZV, may be valid biomarkers of tumor response to treatment with bevacizumab, before change in volume.

Purpose: To compare [ 18 F]-fluorodeoxyglucose (FDG) and [ 18 F]-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) with whole-body magnetic resonance with diffusion-weighted imaging (WB-MRI), for endocrine therapy response prediction at 8 weeks in bone-predominant metastatic breast cancer., Patients and Methods: Thirty-one patients scheduled for endocrine therapy had up to five bone metastases measured [FDG, NaF PET/CT: maximum standardized uptake value (SUV max ); WB-MRI: median apparent diffusion coefficient (ADC med )] at baseline and 8 weeks. To detect the flare phenomenon, a 12-week NaF PET/CT was also performed if 8-week SUV max increased. A 25% parameter change differentiated imaging progressive disease (PD) from non-PD and was compared to a 24-week clinical reference standard and progression-free survival (PFS)., Results: Twenty-two patients (median age, 58.6 years, range, 40-79 years) completing baseline and 8-week imaging were included in the final analysis. Per-patient % change in NaF SUV max predicted 24-week clinical PD with sensitivity, specificity and accuracy of 60, 73.3, and 70%, respectively. For FDG SUV max the results were 0, 100, and 76.2% and for ADC med , 0, 100 and 72.2%, respectively. PFS < 24 weeks was associated with % change in SUV max (NaF: 41.7 vs. 0.7%, p = 0.039; FDG: - 4.8 vs. - 28.6%, p = 0.005) but not ADC med (- 0.5 vs. 10.1%, p = 0.098). Interlesional response heterogeneity occurred in all modalities and NaF flare occurred in seven patients., Conclusions: FDG PET/CT and WB-MRI best predicted clinical non-PD and both FDG and NaF PET/CT predicted PFS < 24 weeks. Lesional response heterogeneity occurs with all modalities and flare is common with NaF PET/CT.

Purpose: Despite the growing use of fluorine-18-fluorodeoxyglucose (F-FDG) PET texture analysis to measure intratumoural heterogeneity in cancer research, the biologic basis of F-FDG PET-derived texture variables is poorly understood. We aimed to assess correlations between F-FDG PET-derived texture variables and whole-slide image (WSI)-derived metrics of tumour cellularity and spatial heterogeneity., Patients and Methods: Twenty-two patients with non-small-cell lung cancer prospectively underwent F-FDG PET imaging before tumour resection. We tested nine F-FDG PET parameters: metabolically active tumour volume, total lesion glycolysis, mean standardized uptake value (SUVmean), first-order entropy, energy, skewness, kurtosis, grey-level co-occurrence matrix entropy and lacunarity (SUV-lacunarity). From the haematoxylin and eosin-stained WSIs, we derived mean tumour-cell density (MCD) and lacunarity (path-lacunarity). Spearman's correlation analysis and agglomerative hierarchical clustering were performed to assess variable associations., Results: Tumour volumes ranged from 2.2 to 74 cm (median: 17.9 cm). MCD correlated positively with total lesion glycolysis (rs: 0.46, P: 0.007) and SUVmean (rs : 0.55; P: 0.008) and negatively with skewness and kurtosis (rs: -0.47 for both; P: 0.028 and 0.026, respectively). SUV-lacunarity and path-lacunarity were positively correlated (rs: 0.5; P: 0.018). On cluster analysis, larger tumours trended towards higher SUVmean and entropy with a predominance of tightly concentrated high SUV-voxels (negative skewness and low kurtosis on the histogram); on WSI analysis such larger tumours also displayed generally higher MCD and low SUV-lacunarity and path-lacunarity., Conclusion: Our data suggest that histopathological MCD and lacunarity are associated with several commonly used F-FDG PET-derived indices including SUV-lacunarity, metabolically active tumour volume, SUVmean, entropy, skewness, and kurtosis, and thus may explain the biological basis of F-FDG PET-uptake heterogeneity in non-small-cell lung cancer.

Objectives: To undertake a systematic review to determine the diagnostic performance of whole body MRI (WBMRI) including diffusion weighted sequences (DWI) compared to whole body computed tomography (WBCT) or 18 F-fluorodeoxyglucose positron emission tomography/CT ( 18 F-FDG PET/CT) in patients with myeloma., Methods: Two researchers searched the primary literature independently for WBMRI studies of myeloma. Data were extracted focusing on the diagnostic ability of WBMRI versus WBCT and 18 F-FDG PET/CT. Meta-analysis was intended., Results: 6 of 2857 articles were eligible that included 147 patients, published from 2008 to 2016. Studies were heterogeneous including both newly diagnosed & relapsed patients. All were single centre studies. Four of the six studies (66.7%) accrued prospectively and 5/6 (83.3%, 3 prospective) included WBMRI and 18 F-FDG PET/CT. Three of seven (42.9%) included DWI. The lack of an independent reference standard for individual lesions was noted in 5/6 (83.3%) studies. Studies reported that WBMRI detected more lesions than 18 F-FDG PET/CT (sensitivity 68-100% versus 47-100%) but was less specific (specificity 37-83% versus 62-85.7%). No paper assessed impact on management., Conclusions: Studies were heterogeneous, the majority lacking an independent reference standard. Future prospective trials should address these limitations and assess the impact of WBMRI on management., (Copyright © 2018. Published by Elsevier B.V.)

Purpose: Measurement of heterogeneity in 18 F-fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET) images is reported to improve tumour phenotyping and response assessment in a number of cancers. We aimed to determine whether measurements of 18 F-FDG heterogeneity could improve differentiation of benign symptomatic neurofibromas from malignant peripheral nerve sheath tumours (MPNSTs)., Methods: 18 F-FDG PET data from a cohort of 54 patients (24 female, 30 male, mean age 35.1 years) with neurofibromatosis-1 (NF1), and clinically suspected malignant transformation of neurofibromas into MPNSTs, were included. Scans were performed to a standard clinical protocol at 1.5 and 4 h post-injection. Six first-order [including three standardised uptake value (SUV) parameters], four second-order (derived from grey-level co-occurrence matrices) and four high-order (derived from neighbourhood grey-tone difference matrices) statistical features were calculated from tumour volumes of interest. Each patient had histological verification or at least 5 years clinical follow-up as the reference standard with regards to the characterisation of tumours as benign (n = 30) or malignant (n = 24)., Results: There was a significant difference between benign and malignant tumours for all six first-order parameters (at 1.5 and 4 h; p < 0.0001), for second-order entropy (only at 4 h) and for all high-order features (at 1.5 h and 4 h, except contrast at 4 h; p < 0.0001-0.047). Similarly, the area under the receiver operating characteristic curves was high (0.669-0.997, p < 0.05) for the same features as well as 1.5-h second-order entropy. No first-, second- or high-order feature performed better than maximum SUV (SUVmax) at differentiating benign from malignant tumours., Conclusions: 18 F-FDG uptake in MPNSTs is higher than benign symptomatic neurofibromas, as defined by SUV parameters, and more heterogeneous, as defined by first- and high-order heterogeneity parameters. However, heterogeneity analysis does not improve on SUVmax discriminative performance.

Purpose: To determine if first-order and high-order textural features on fluorine 18 ((18)F) fluorodeoxyglucose (FDG) positron emission tomography (PET) images of non-small cell lung cancer (NSCLC) (a) at baseline, (b) at 6 weeks, or (c) the percentage change between baseline and 6 weeks can predict response or survival in patients treated with erlotinib., Materials and Methods: Institutional review board approval was obtained for post hoc analysis of data from a prospective single-center study for which informed consent was obtained. The study included 47 patients with NSCLC who underwent (18)F-FDG PET/computed tomography (CT) at baseline (n = 47) and 6 weeks (n = 40) after commencing treatment with erlotinib. First-order and high-order primary tumor texture features reflecting image heterogeneity, standardized uptake values, metabolic tumor volume, and total lesion glycolysis were measured for all (18)F-FDG PET studies. Response to erlotinib was assessed by using the Response Evaluation Criteria in Solid Tumors (RECIST) on CT images obtained at 12 weeks (n = 32). Associations between PET parameters, overall survival (OS), and RECIST-based treatment response were tested by Cox and logistic regression analyses, respectively., Results: Median OS was 14.1 months. According to CT RECIST at 12 weeks, there were 21 nonresponders and 11 responders. Response to erlotinib was associated with reduced heterogeneity (first-order standard deviation, P = .01; entropy, P = .001; uniformity, P = .001). At multivariable analysis, high-order contrast at 6 weeks (P = .002) and percentage change in first-order entropy (P = .03) were independently associated with survival. Percentage change in first-order entropy was also independently associated with treatment response (P = .01)., Conclusion: Response to erlotinib is associated with reduced heterogeneity at (18)F-FDG PET. Changes in first-order entropy are independently associated with OS and treatment response.

Objectives: Measuring tumour heterogeneity by textural analysis in (18)F-fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) provides predictive and prognostic information but technical aspects of image processing can influence parameter measurements. We therefore tested effects of image smoothing, segmentation and quantisation on the precision of heterogeneity measurements., Methods: Sixty-four (18)F-FDG PET/CT images of oesophageal cancer were processed using different Gaussian smoothing levels (2.0, 2.5, 3.0, 3.5, 4.0 mm), maximum standardised uptake value (SUVmax) segmentation thresholds (45%, 50%, 55%, 60%) and quantisation (8, 16, 32, 64, 128 bin widths). Heterogeneity parameters included grey-level co-occurrence matrix (GLCM), grey-level run length matrix (GLRL), neighbourhood grey-tone difference matrix (NGTDM), grey-level size zone matrix (GLSZM) and fractal analysis methods. The concordance correlation coefficient (CCC) for the three processing variables was calculated for each heterogeneity parameter., Results: Most parameters showed poor agreement between different bin widths (CCC median 0.08, range 0.004-0.99). Segmentation and smoothing showed smaller effects on precision (segmentation: CCC median 0.82, range 0.33-0.97; smoothing: CCC median 0.99, range 0.58-0.99)., Conclusions: Smoothing and segmentation have only a small effect on the precision of heterogeneity measurements in (18)F-FDG PET data. However, quantisation often has larger effects, highlighting a need for further evaluation and standardisation of parameters for multicentre studies., Key Points: • Heterogeneity measurement precision in (18) F-FDG PET is influenced by image processing methods. • Quantisation shows large effects on precision of heterogeneity parameters in (18) F-FDG PET/CT. • Smoothing and segmentation show comparatively smaller effects on precision of heterogeneity parameters.

Methods: Thirty patients with proven colorectal cancer prospectively underwent integrated 18F-FDG PET/DCE-CT to assess the metabolic-flow phenotype. Both CT blood flow parametric maps and PET images were analyzed. Correlations between PET heterogeneity and perfusion CT were assessed by Spearman's rank correlation analysis., Results: Blood flow visualization provided by DCE-CT images was significantly correlated with 18F-FDG PET metabolically active tumor volume as well as with uptake heterogeneity for patients with stage III/IV tumors (|ρ|:0.66 to 0.78; p-value<0.02)., Conclusion: The positive correlation found with tumor blood flow indicates that intra-tumor heterogeneity of 18F-FDG PET accumulation reflects to some extent tracer distribution and consequently indicates that 18F-FDG PET intra-tumor heterogeneity may be associated with physiological processes such as tumor vascularization.

Purpose: Malignant pleural mesothelioma (MPM) is a disease with poor prognosis despite multimodal therapy but there is variation in survival between patients. Prognostic information is therefore potentially valuable in managing patients, particularly in the context of clinical trials where patients could be stratified according to risk. Therefore we have evaluated the prognostic ability of parameters derived from baseline 2-[(18)F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography ((18)F-FDG PET/CT)., Methods: In order to determine the relationships between metabolic activity and prognosis we reviewed all (18)F-FDG PET/CT scans used for pretreatment staging of MPM patients in our institution between January 2005 and December 2011 (n = 60) and measured standardised uptake values (SUV) including mean, maximum and peak values, metabolic tumour volume (MTV) and total lesion glycolysis (TLG). Overall survival (OS) or time to last censor was recorded, as well as histological subtypes., Results: Median follow-up was 12.7 months (1.9-60.9) and median OS was 14.1 months (1.9-54.9). By univariable analysis histological subtype (p = 0.013), TLG (p = 0.024) and MTV (p = 0.038) were significantly associated with OS and SUVmax was borderline (p = 0.051). On multivariable analysis histological subtype and TLG were associated with OS but at borderline statistical significance (p = 0.060 and 0.058, respectively). No statistically significant differences in any PET parameters were found between the epithelioid and non-epithelioid histological subtypes., Conclusion: (18)F-FDG PET/CT parameters that take into account functional volume (MTV, TLG) show significant associations with survival in patients with MPM before adjusting for histological subtype and are worthy of further evaluation to determine their ability to stratify patients in clinical trials.

Unlabelled: There is evidence in some solid tumors that textural features of tumoral uptake in (18)F-FDG PET images are associated with response to chemoradiotherapy and survival. We have investigated whether a similar relationship exists in non-small cell lung cancer (NSCLC)., Methods: Fifty-three patients (mean age, 65.8 y; 31 men, 22 women) with NSCLC treated with chemoradiotherapy underwent pretreatment (18)F-FDG PET/CT scans. Response was assessed by CT Response Evaluation Criteria in Solid Tumors (RECIST) at 12 wk. Overall survival (OS), progression-free survival (PFS), and local PFS (LPFS) were recorded. Primary tumor texture was measured by the parameters coarseness, contrast, busyness, and complexity. The following parameters were also derived from the PET data: primary tumor standardized uptake values (SUVs) (mean SUV, maximum SUV, and peak SUV), metabolic tumor volume, and total lesion glycolysis., Results: Compared with nonresponders, RECIST responders showed lower coarseness (mean, 0.012 vs. 0.027; P = 0.004) and higher contrast (mean, 0.11 vs. 0.044; P = 0.002) and busyness (mean, 0.76 vs. 0.37; P = 0.027). Neither complexity nor any of the SUV parameters predicted RECIST response. By Kaplan-Meier analysis, OS, PFS, and LPFS were lower in patients with high primary tumor coarseness (median, 21.1 mo vs. not reached, P = 0.003; 12.6 vs. 25.8 mo, P = 0.002; and 12.9 vs. 20.5 mo, P = 0.016, respectively). Tumor coarseness was an independent predictor of OS on multivariable analysis. Contrast and busyness did not show significant associations with OS (P = 0.075 and 0.059, respectively), but PFS and LPFS were longer in patients with high levels of each (for contrast: median of 20.5 vs. 12.6 mo, P = 0.015, and median not reached vs. 24 mo, P = 0.02; and for busyness: median of 20.5 vs. 12.6 mo, P = 0.01, and median not reached vs. 24 mo, P = 0.006). Neither complexity nor any of the SUV parameters showed significant associations with the survival parameters., Conclusion: In NSCLC, baseline (18)F-FDG PET scan uptake showing abnormal texture as measured by coarseness, contrast, and busyness is associated with nonresponse to chemoradiotherapy by RECIST and with poorer prognosis. Measurement of tumor metabolic heterogeneity with these parameters may provide indices that can be used to stratify patients in clinical trials for lung cancer chemoradiotherapy.

(18)F-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) is now routinely used in oncological imaging for diagnosis and staging and increasingly to determine early response to treatment, often employing semiquantitative measures of lesion activity such as the standardized uptake value (SUV). However, the ability to predict the behaviour of a tumour in terms of future therapy response or prognosis using SUVs from a baseline scan prior to treatment is limited. It is recognized that medical images contain more useful information than may be perceived with the naked eye, leading to the field of "radiomics" whereby additional features can be extracted by computational postprocessing techniques. In recent years, evidence has slowly accumulated showing that parameters obtained by texture analysis of radiological images, reflecting the underlying spatial variation and heterogeneity of voxel intensities within a tumour, may yield additional predictive and prognostic information. It is hoped that measurement of these textural features may allow better tissue characterization as well as better stratification of treatment in clinical trials, or individualization of future cancer treatment in the clinic, than is possible with current imaging biomarkers. In this review we focus on the literature describing the emerging methods of texture analysis in (18)FDG PET/CT, as well as other imaging modalities, and how the measurement of spatial variation of voxel grey-scale intensity within an image may provide additional predictive and prognostic information, and postulate the underlying biological mechanisms.

Objective: The purpose of this article is to assess the effect of observers on combined metabolic-vascular parameters in colorectal cancer., Subjects and Methods: Twenty-five prospective patients (12 men and 13 women; mean age, 66.9 years) with proven primary colorectal adenocarcinoma underwent integrated (18)F-FDG PET/perfusion CT to assess tumor metabolism (mean and maximum standardized uptake value [SUV(mean) and SUV(max), respectively]) and vascularization (blood flow [BF], blood volume [BV], permeability surface-area product, and standardized perfusion value). Intra- and interobserver agreement for PET, perfusion CT, and combined metabolic-flow parameters were determined by Bland-Altman statistics and intraclass correlation coefficients (ICCs)., Results: The mean tumor size was 3.8 ± 1.6 cm; there were five stage IA/B, six stage IIA/B, eight stage IIIA/B, and six stage IV tumors. Intra- and interobserver agreement for individual parameters was fair to good, with mean differences between observers of -0.74 for SUV(max), -0.16 for SUV(mean), 9.72 for BF, 0.15 for BV, -0.76 for permeability surface-area product, and 0.09 for standardized perfusion value. ICCs were 0.44-0.99 and 0.38-0.89 for intra- and interobserver agreement, respectively. Interobserver agreement was variable for combined metabolic-flow parameters but better for metabolic-flow difference than for metabolic-flow ratio: ICCs were 0.69-0.88 for the metabolic-flow difference and 0.44-0.94 for the metabolic-flow ratio., Conclusion: Combined parameters to assess the metabolic-flow relationship are influenced by observer variation. Intra- and interobserver agreement are better for the metabolic-flow differences than for the ratios, suggesting that metabolic-flow differences may be a more robust parameter for clinical practice.

Unlabelled: The aim of this study was to assess the in vivo flow-metabolic phenotype in primary colorectal cancer with integrated (18)F-FDG PET/perfusion CT and its relationship to gold standard histopathologic assessment of angiogenesis and hypoxia., Methods: 45 patients (26 male and 19 female; mean age, 67.6 y) with primary colorectal cancer underwent integrated (18)F-FDG PET/perfusion CT, deriving tumor glucose metabolism (maximum standardized uptake value) and regional blood flow. From this cohort, 35 underwent surgery subsequently, without intervening neoadjuvant treatment, allowing histopathologic correlation with tumor stage, CD105 microvessel density, vascular endothelial growth factor (VEGF), glucose transporter protein 1 (Glut-1), and hypoxia-inducible factor 1 expression., Results: The flow-metabolic ratio was significantly lower for tumors with higher VEGF (3.65 vs. 5.98; P = 0.01) or hypoxia-inducible factor 1 expression (3.63 vs. 5.48; P = 0.04) versus tumors with lower expression. There were significant negative correlations between the tumor flow-metabolic ratio and VEGF expression (r = -0.55, P = 0.0008), indicating that tumors with low blood flow but higher metabolism were associated with higher VEGF expression. Flow and metabolism were coupled in higher-stage (stage III/IV) tumors but not lower-stage tumors (stage I/II) (r = 0.47, P = 0.03, vs. r = 0.09, P = 0.65, respectively., Conclusion: Tumors with a low-flow-high-metabolism phenotype demonstrated higher VEGF expression and may reflect a more angiogenic phenotype.

Unlabelled: Inflammation and angiogenesis are hypothesized to be important factors contributing to plaque vulnerability, whereas calcification is suggested to confer stability. To investigate this in vivo, we combined CT angiography and PET and compared the findings with immunohistochemistry for patients undergoing carotid endarterectomy., Methods: Twenty-one consecutive patients (18 men, 3 women; mean age ± SD, 68.3 ± 7.3) undergoing carotid endarterectomy were recruited for combined carotid (18)F-FDG PET/CT angiography. Plaque (18)F-FDG uptake was quantified with maximum standardized uptake value, and CT angiography quantified percentage plaque composition (calcium and lipid). Surgical specimens underwent ex vivo CT aiding image registration, followed by immunohistochemical staining for CD68 (macrophage density) and vascular endothelial growth factor (angiogenesis). Relationships between imaging and immunohistochemistry were assessed with Spearman rank correlation and multivariable regression., Results: The mean (±SD) surgically excised carotid plaque (18)F-FDG metabolism was 2.4 (±0.5) versus 2.2 (±0.3) contralaterally (P = 0.027). There were positive correlations between plaque (18)F-FDG metabolism and immunohistochemistry with CD68 (ρ = 0.55; P = 0.011) and vascular endothelial growth factor (ρ = 0.47; P = 0.031). There was an inverse relationship between plaque (18)F-FDG metabolism and plaque percentage calcium composition on CT (ρ = -0.51; P = 0.018) and between calcium composition and immunohistochemistry with CD68 (ρ = -0.57; P = 0.007). Regression showed that maximum standardized uptake value and calcium composition were independently significant predictors of angiogenesis, and calcium composition was a predictor of macrophage density., Conclusion: We provide in vivo evidence that increased plaque metabolism is associated with increased biomarkers of angiogenesis and inflammation, whereas plaque calcification is inversely related to PET and histologic biomarkers of inflammation.

Background Radiomic features may quantify characteristics present in medical imaging. However, the lack of standardized definitions and validated reference values have hampered clinical use. Purpose To standardize a set of 174 radiomic features. Materials and Methods Radiomic features were assessed in three phases. In phase I, 487 features were derived from the basic set of 174 features. Twenty-five research teams with unique radiomics software implementations computed feature values directly from a digital phantom, without any additional image processing. In phase II, 15 teams computed values for 1347 derived features using a CT image of a patient with lung cancer and predefined image processing configurations. In both phases, consensus among the teams on the validity of tentative reference values was measured through the frequency of the modal value and classified as follows: less than three matches, weak; three to five matches, moderate; six to nine matches, strong; 10 or more matches, very strong. In the final phase (phase III), a public data set of multimodality images (CT, fluorine 18 fluorodeoxyglucose PET, and T1-weighted MRI) from 51 patients with soft-tissue sarcoma was used to prospectively assess reproducibility of standardized features. Results Consensus on reference values was initially weak for 232 of 302 features (76.8%) at phase I and 703 of 1075 features (65.4%) at phase II. At the final iteration, weak consensus remained for only two of 487 features (0.4%) at phase I and 19 of 1347 features (1.4%) at phase II. Strong or better consensus was achieved for 463 of 487 features (95.1%) at phase I and 1220 of 1347 features (90.6%) at phase II. Overall, 169 of 174 features were standardized in the first two phases. In the final validation phase (phase III), most of the 169 standardized features could be excellently reproduced (166 with CT; 164 with PET; and 164 with MRI). Conclusion A set of 169 radiomics features was standardized, which enabled verification and calibration of different radiomics software. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kuhl and Truhn in this issue.

Objectives: Radiomic models present an avenue to improve oesophageal adenocarcinoma assessment through quantitative medical image analysis. However, model selection is complicated by the abundance of available predictors and the uncertainty of their relevance and reproducibility. This analysis reviews recent research to facilitate precedent-based model selection for prospective validation studies. Methods: This analysis reviews research on 18F-FDG PET/CT, PET/MRI and CT radiomics in oesophageal adenocarcinoma between 2016 and 2021. Model design, testing and reporting are evaluated according to the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) score and Radiomics Quality Score (RQS). Key results and limitations are analysed to identify opportunities for future research in the area. Results: Radiomic models of stage and therapeutic response demonstrated discriminative capacity, though clinical applications require greater sensitivity. Although radiomic models predict survival within institutions, generalisability is limited. Few radiomic features have been recommended independently by multiple studies. Conclusions: Future research must prioritise prospective validation of previously proposed models to further clinical translation. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine if 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) features are associated with contemporaneous metastases in patients with oesophageal/gastroesophageal cancer. Methods: Following IRB approval and informed consent, patients underwent a staging PET/MRI following 18F-FDG injection (326 ± 28 MBq) and 156 ± 23 min uptake time. First-order histogram and second-order grey level co-occurrence matrix features were computed for PET standardized uptake value (SUV) and MRI T1-W, T2-W, diffusion weighted (DWI) and apparent diffusion coefficient (ADC) images for the whole tumour volume. K-means clustering assessed the correlation of feature-pairs with metastases. Multivariate analysis of variance (MANOVA) was performed to assess the statistical separability of the groups identified by feature-pairs. Sensitivity (SN), specificity (SP), positive predictive value (PPV), negative predictive value (NPV), and accuracy (ACC) were calculated for these features and compared with SUVmax, ADCmean and maximum diameter alone for predicting contemporaneous metastases. Results: Twenty patients (18 males, 2 female; median 67 years, range 52–86) comprised the final study cohort; ten patients had metastases. Lower second-order SUV entropy combined with higher second-order ADC entropy were the best feature-pair for discriminating metastatic patients, MANOVA p value <0.001 (SN = 80%, SP = 80%, PPV = 80%, NPV = 80%, ACC = 80%). SUVmax (SN = 30%, SP = 80%, PPV = 60%, NPV = 53%, ACC = 55%), ADCmean (SN = 20%, SP = 70%, PPV = 40%, NPV = 47%, ACC = 45%) and tumour maximum diameter (SN = 10%, SP = 90%, PPV = 50%, NPV = 50%, ACC = 50%) had poorer sensitivity and accuracy. Conclusion: High ADC entropy combined with low SUV entropy is associated with a higher prevalence of metastases and a promising initial signature for future study. [ABSTRACT FROM AUTHOR]

Purpose: To compare [18F]-fluorodeoxyglucose (FDG) and [18F]-sodium fluoride (NaF) positron emission tomography/computed tomography (PET/CT) with whole-body magnetic resonance with diffusion-weighted imaging (WB-MRI), for endocrine therapy response prediction at 8 weeks in bone-predominant metastatic breast cancer. Patients and methods: Thirty-one patients scheduled for endocrine therapy had up to five bone metastases measured [FDG, NaF PET/CT: maximum standardized uptake value (SUVmax); WB-MRI: median apparent diffusion coefficient (ADCmed)] at baseline and 8 weeks. To detect the flare phenomenon, a 12-week NaF PET/CT was also performed if 8-week SUVmax increased. A 25% parameter change differentiated imaging progressive disease (PD) from non-PD and was compared to a 24-week clinical reference standard and progression-free survival (PFS). Results: Twenty-two patients (median age, 58.6 years, range, 40–79 years) completing baseline and 8-week imaging were included in the final analysis. Per-patient % change in NaF SUVmax predicted 24-week clinical PD with sensitivity, specificity and accuracy of 60, 73.3, and 70%, respectively. For FDG SUVmax the results were 0, 100, and 76.2% and for ADCmed, 0, 100 and 72.2%, respectively. PFS < 24 weeks was associated with % change in SUVmax (NaF: 41.7 vs. 0.7%, p = 0.039; FDG: − 4.8 vs. − 28.6%, p = 0.005) but not ADCmed (− 0.5 vs. 10.1%, p = 0.098). Interlesional response heterogeneity occurred in all modalities and NaF flare occurred in seven patients. Conclusions: FDG PET/CT and WB-MRI best predicted clinical non-PD and both FDG and NaF PET/CT predicted PFS < 24 weeks. Lesional response heterogeneity occurs with all modalities and flare is common with NaF PET/CT. [ABSTRACT FROM AUTHOR]

Purpose: Measurement of heterogeneity in F-fluorodeoxyglucose (F-FDG) positron emission tomography (PET) images is reported to improve tumour phenotyping and response assessment in a number of cancers. We aimed to determine whether measurements of F-FDG heterogeneity could improve differentiation of benign symptomatic neurofibromas from malignant peripheral nerve sheath tumours (MPNSTs). Methods: F-FDG PET data from a cohort of 54 patients (24 female, 30 male, mean age 35.1 years) with neurofibromatosis-1 (NF1), and clinically suspected malignant transformation of neurofibromas into MPNSTs, were included. Scans were performed to a standard clinical protocol at 1.5 and 4 h post-injection. Six first-order [including three standardised uptake value (SUV) parameters], four second-order (derived from grey-level co-occurrence matrices) and four high-order (derived from neighbourhood grey-tone difference matrices) statistical features were calculated from tumour volumes of interest. Each patient had histological verification or at least 5 years clinical follow-up as the reference standard with regards to the characterisation of tumours as benign ( n = 30) or malignant ( n = 24). Results: There was a significant difference between benign and malignant tumours for all six first-order parameters (at 1.5 and 4 h; p < 0.0001), for second-order entropy (only at 4 h) and for all high-order features (at 1.5 h and 4 h, except contrast at 4 h; p < 0.0001-0.047). Similarly, the area under the receiver operating characteristic curves was high (0.669-0.997, p < 0.05) for the same features as well as 1.5-h second-order entropy. No first-, second- or high-order feature performed better than maximum SUV (SUVmax) at differentiating benign from malignant tumours. Conclusions: F-FDG uptake in MPNSTs is higher than benign symptomatic neurofibromas, as defined by SUV parameters, and more heterogeneous, as defined by first- and high-order heterogeneity parameters. However, heterogeneity analysis does not improve on SUVmax discriminative performance. [ABSTRACT FROM AUTHOR]

Background: Tyrosine kinase inhibitors are the first line standard of care for treatment of metastatic renal cell carcinoma (RCC). Accurate response assessment in the setting of antiangiogenic therapies remains suboptimal as standard size-related response criteria do not necessarily accurately reflect clinical benefit, as they may be less pronounced or occur later in therapy than devascularisation. The challenge for imaging is providing timely assessment of disease status allowing therapies to be tailored to ensure ongoing clinical benefit. We propose that combined assessment of morphological, physiological and metabolic imaging parameters using 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI) will better reflect disease behaviour, improving assessment of response/non-response/relapse.Methods/design: The REMAP study is a single-centre prospective observational study. Eligible patients with metastatic renal cell carcinoma, planned for systemic therapy, with at least 2 lesions will undergo an integrated 18F-FDG PET and MRI whole body imaging with diffusion weighted and contrast-enhanced multiphasic as well as standard anatomical MRI sequences at baseline, 12 weeks and 24 weeks of systemic therapy allowing 18F-FDG standardised uptake value (SUV), apparent diffusion co-efficient (ADC) and normalised signal intensity (SI) parameters to be obtained. Standard of care contrast-enhanced computed tomography CT scans will be performed at equivalent time-points. CT response categorisation will be performed using RECIST 1.1 and alternative (modified)Choi and MASS criteria. The reference standard for disease status will be by consensus panel taking into account clinical, biochemical and conventional imaging parameters. Intra- and inter-tumoural heterogeneity in vascular, diffusion and metabolic response/non-response will be assessed by image texture analysis. Imaging will also inform the development of computational methods for automated disease status categorisation.Discussion: The REMAP study will demonstrate the ability of integrated 18F-FDG PET-MRI to provide a more personalised approach to therapy. We suggest that 18F-FDG PET/MRI will provide superior sensitivity and specificity in early response/non-response categorisation when compared to standard CT (using RECIST 1.1 and alternative (modified)Choi or MASS criteria) thus facilitating more timely and better informed treatment decisions.Trial Registration: The trial is approved by the Southeast London Research Ethics Committee reference 16/LO/1499 and registered on the NIHR clinical research network portfolio ISRCTN12114913 . [ABSTRACT FROM AUTHOR]

Cross-sectional imaging is now recommended by the National Institute for Health and Care Excellence (NICE) for patients with suspected and newly diagnosed myeloma instead of skeletal survey. The objectives of this study were: (1) To evaluate compliance of current UK imaging practice with reference to National Institute for Health and Care Excellence best-practice clinical guidelines for plasma cell malignancies. (2) To identify factors which may influence diagnostic imaging choices. We conducted a national online survey to assess compliance with guidelines and to identify challenges to implementation (endorsed by Myeloma UK, UK Myeloma Forum and the British Society of Skeletal Radiologists). Responses were received from 31 district general and 28 teaching hospitals. For suspected and confirmed myeloma, skeletal survey remained the most frequent first-line imaging test (suspected myeloma 44.3%, confirmed myeloma 37.7%). Only 9.8 % of responders offered first-line whole body MRI. Significant challenges remain to standardisation of imaging practice in accordance with national best-practice guidelines. This is the first publication to date evaluating current UK imaging practice for assessing myeloma since the publication of new guidelines recommending use of advanced cross-sectional imaging techniques. Skeletal survey remains the most commonly performed first-line imaging test in patients with suspected or confirmed myeloma and this is largely due to resource limitations within radiology departments. [ABSTRACT FROM AUTHOR]

Purpose: Radiomics describes the extraction of multiple, otherwise invisible, features from medical images that, with bioinformatic approaches, can be used to provide additional information that can predict underlying tumor biology and behavior.Methods and Materials: Radiomic signatures can be used alone or with other patient-specific data to improve tumor phenotyping, treatment response prediction, and prognosis, noninvasively. The data describing 18F-fluorodeoxyglucose positron emission tomography radiomics, often using texture or heterogeneity parameters, are increasing rapidly.Results: In relation to radiation therapy practice, early data have reported the use of radiomic approaches to better define tumor volumes and predict radiation toxicity and treatment response.Conclusions: Although at an early stage of development, with many technical challenges remaining and a need for standardization, promise nevertheless exists that PET radiomics will contribute to personalized medicine, especially with the availability of increased computing power and the development of machine-learning approaches for imaging. [ABSTRACT FROM AUTHOR]

18F-fluorodeoxyglucose (18F-FDG) positron emission tomography–computed tomography (PET/CT) is established for characterising indeterminate pulmonary nodules and staging lung cancer where there is curative intent. Whilst a sensitive technique, specificity for characterising lung cancer is limited. There is recognition that evaluation of other aspects of abnormal cancer biology in addition to glucose metabolism may be more helpful in characterising tumours and predicting response to novel targeted cancer therapeutics. Therefore, efforts have been made to develop and evaluate new radiopharmaceuticals in order to improve the sensitivity and specificity of PET imaging in lung cancer with regards to characterisation, treatment stratification and therapeutic monitoring. 18F-fluorothymidine (18F-FLT) is a marker of cellular proliferation. It shows a lower accumulation in tumours than 18F-FDG as it only accumulates in the cells that are in the S phase of growth and demonstrates a low sensitivity for nodal staging. Its main role is in evaluating treatment response. Methionine is an essential amino acid. 11C-methionine is more specific and sensitive than 18F-FDG in differentiating benign and malignant thoracic nodules. 18Ffluoromisonidazole (18F-FMISO) is used for imaging tumour hypoxia. Tumour response to treatment is significantly related to the level of tumour oxygenation. Angiogenesis is the process by which new blood vessels are formed in tumours and is involved in tumour growth and metastatic tumour spread and is a therapeutic target. Most clinical studies have focused on targeted integrin PET imaging of which αvβ3 integrin is the most extensively investigated. It is upregulated on activated endothelial cells in association with tumour angiogenesis. Neuroendocrine tumour tracers, particularly 68Ga-DOTA-peptides, have an established role in imaging of carcinoid tumours. Whilst most of these tracers have predominantly been used in the research environment, they offer exciting opportunities for improving staging, characterisation, stratification and response assessment in an era of increased personalised therapy in lung cancer. [ABSTRACT FROM AUTHOR]