Can FDG-PET/CT imaging be used to predict decline in quality of life in interstitial lung disease? A prospective study of the relationship between FDG uptake and quality of life in a UK outpatient setting.

BACKGROUND: 18Fluorine-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET) CT imaging has been used in many inflammatory and infectious conditions to differentiate areas of increased metabolic activity. FDG uptake differs between areas of normal lung parenchyma and interstitial lung disease (ILD). OBJECTIVES: In this study, we investigated whether FDG-PET/CT parameters were associated with a change in the quality of life (QoL) in patients with ILD over 4 years of follow-up. METHODS: Patients underwent PET-CT imaging at diagnosis and were followed up with annual QoL assessment using the St George's Respiratory Questionnaire (SGRQ) until death or 4 years of follow-up. Maximum standard uptake value (SUVmax) and Tissue-to-Background Ratio (TBR) were assessed against SGRQ overall and subscale scores. RESULTS: 193 patients (94 patients in the idiopathic pulmonary fibrosis (IPF) subgroup and 99 patients in the non-IPF subgroup) underwent baseline FDG-PET/CT imaging and QoL assessment. Weak-to-moderate correlation was observed between baseline SUVmax and SGRQ scores in both ILD subgroups. No relationship was observed between baseline SUVmax or TBR and change in SGRQ scores over 4 years of follow-up. In the IPF subgroup, surviving patients reported a decline in QoL at 4 years post diagnosis whereas an improvement in QoL was seen in surviving patients with non-IPF ILD. CONCLUSIONS: Weak-to-moderate positive correlation between baseline SUVmax and SGRQ scores was observed in both ILD subgroups (IPF:rs=0.187, p=0.047, non-IPF: rs=0.320, p=0.001). However, baseline SUVmax and TBR were not associated with change in QoL in patients with IPF and non-IPF ILD over 4 years of follow-up. At 4 years post diagnosis, surviving patients with IPF reported declining QoL whereas improvement was seen in patients with ILD who did not have IPF.

[18F]FDG PET/CT Signal Correlates with Neoangiogenesis Markers in Patients with Fibrotic Interstitial Lung Disease Who Underwent Lung Biopsy: Implication for the Use of PET/CT in Diffuse Lung Diseases.

The use of [18F]FDG PET/CT as a biomarker in diffuse lung diseases is increasingly recognized. We investigated the correlation between [18F]FDG uptake with histologic markers on lung biopsy of patients with fibrotic interstitial lung disease (fILD). Methods: We recruited 18 patients with fILD awaiting lung biopsy for [18F]FDG PET/CT. We derived a target-to-background ratio (TBR) of maximum pulmonary uptake of [18F]FDG (SUVmax) divided by the lung background (SUVmin). Consecutive paraffin-embedded lung biopsy sections were immunostained for alveolar and interstitial macrophages (CD68), microvessel density (MVD) (CD31 and CD105/endoglin), and glucose transporter 1. MVD was expressed as vessel area percentage per high-power field (Va%/hpf). Differences in imaging and angiogenesis markers between histologic usual interstitial pneumonia (UIP) and non-UIP were assessed using a nonparametric Mann-Whitney test. Correlation of imaging with angiogenesis markers was assessed using the nonparametric Spearman rank correlation. Univariate Kaplan-Meier survival analysis assessed the difference in the survival curves for each of the angiogenesis markers (separated by their respective optimal cutoff) using the log-rank test. Statistical analysis was performed using SPSS. Results: In total, 18 patients were followed for an average of 41.36 mo (range, 5.69-132.46 mo; median, 30.07 mo). Only CD105 MVD showed a significantly positive correlation with [18F]FDG TBR (Spearman rank correlation, 0.556; P < 0.05, n = 13). There was no correlation between [18F]FDG uptake and macrophage expression of glucose transporter 1. CD105 and CD31 were higher for UIP than for non-UIP, with CD105 reaching statistical significance (P = 0.011). In all patients, MVD assessed with either CD105 or CD31 quantification on biopsy predicted overall survival. Patients with CD105 MVD of less than 12 Va%/hpf or CD31 MVD of less than 35 Va%/hpf had a significantly better prognosis (no deaths during follow-up in the case of CD105) than did patients with higher scores of CD105 MVD (median survival, 35 mo; P = 0.041, n = 13) or CD31 MVD (median survival, 28 mo; P = 0.014, n = 13). Conclusion: Previous work has used [18F]FDG uptake in PET/CT as a biomarker in fILD. Here, we highlight a correlation between angiogenesis and [18F]FDG TBR. We show that MVD is higher for UIP than for non-UIP and is associated with mortality in patients with fILD. These data set the scene to investigate the potential role of vasculature and angiogenesis in fibrosis.

Machine-Learning-Based Radiomics for Classifying Glioma Grade from Magnetic Resonance Images of the Brain.

Grading of gliomas is a piece of critical information related to prognosis and survival. Classifying glioma grade by semantic radiological features is subjective, requires multiple MRI sequences, is quite complex and clinically demanding, and can very often result in erroneous radiological diagnosis. We used a radiomics approach with machine learning classifiers to determine the grade of gliomas. Eighty-three patients with histopathologically proven gliomas underwent MRI of the brain. Whenever available, immunohistochemistry was additionally used to augment the histopathological diagnosis. Segmentation was performed manually on the T2W MR sequence using the TexRad texture analysis softwareTM, Version 3.10. Forty-two radiomics features, which included first-order features and shape features, were derived and compared between high-grade and low-grade gliomas. Features were selected by recursive feature elimination using a random forest algorithm method. The classification performance of the models was measured using accuracy, precision, recall, f1 score, and area under the curve (AUC) of the receiver operating characteristic curve. A 10-fold cross-validation was adopted to separate the training and the test data. The selected features were used to build five classifier models: support vector machine, random forest, gradient boost, naive Bayes, and AdaBoost classifiers. The random forest model performed the best, achieving an AUC of 0.81, an accuracy of 0.83, f1 score of 0.88, a recall of 0.93, and a precision of 0.85 for the test cohort. The results suggest that machine-learning-based radiomics features extracted from multiparametric MRI images can provide a non-invasive method for predicting glioma grades preoperatively. In the present study, we extracted the radiomics features from a single cross-sectional image of the T2W MRI sequence and utilized these features to build a fairly robust model to classify low-grade gliomas from high-grade gliomas (grade 4 gliomas).

Multi-center evaluation of baseline neutrophil-to-lymphocyte (NLR) ratio as an independent predictor of mortality and clinical risk stratifier in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease trajectory. The aim of this study was to assess the potential of neutrophil-to-lymphocyte ratio (NLR) to predict outcomes in IPF. Methods: We adopted a two-stage discovery (n = 71) and validation (n = 134) design using patients from the UCL partners (UCLp) cohort. We then combined discovery and validation cohorts and included an additional 794 people with IPF, using real-life data from 5 other UK centers, to give a combined cohort of 999 patients. Data were collected from patients presenting over a 13-year period (2006-2019) with mean follow up of 3.7 years (censoring: 2018-2020). Findings: In the discovery analysis, we showed that high values of NLR (>/ = 2.9 vs < 2.9) were associated with increased risk of mortality in IPF (HR 2.04, 95% CI 1.09-3.81, n = 71, p = 0.025). This was confirmed in the validation (HR 1.91, 95% CI 1.15-3.18, n = 134, p = 0.0114) and combined cohorts (HR 1.65, n = 999, 95% CI 1.39-1.95; p < 0·0001). NLR correlated with GAP stage and GAP index (p < 0.0001). Stratifying patients by NLR category (low/high) showed significant differences in survival for GAP stage 2 (p < 0.0001), however not for GAP stage 1 or 3. In a multivariate analysis, a high NLR was an independent predictor of mortality/progression after adjustment for individual GAP components and steroid/anti-fibrotic use (p < 0·03). Furthermore, incorporation of baseline NLR in a modified GAP-stage/index, GAP-index/stage-plus, refined prognostic ability as measured by concordance (C)-index. Interpretation: We have identified NLR as a widely available test that significantly correlates with lung function, can predict outcomes in IPF and refines cohort staging with GAP. NLR may allow timely prioritisation of at-risk patients, even in the absence of lung function. Funding: Breathing Matters, GSK, CF Trust, BLF-Asthma, MRC, NIHR Alpha-1 Foundation.

Dynamic Brain Imaging Response to Spinal Cord Stimulation Differential Frequencies DiFY SCS-PET Clinical Trial.

OBJECTIVES: This study with sequential 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computed tomography (CT) scanning was designed to investigate any objective measurable effect of differential frequency stimulation (40 Hz, 4000 Hz, and 10,000 Hz) on specific pain matrix areas in patients who underwent spinal cord stimulation (SCS) for intractable lumbar neuropathic pain. MATERIALS AND METHODS: In this single-center, randomized, blinded study, four brain 18F-FDG PET scans were performed for each patient-at baseline before SCS implant and after 40-Hz, 4000-Hz, and 10,000-Hz stimulation. After 40-Hz stimulation for four weeks, patients were randomized 1:1 (4000 Hz/10,000 Hz), crossing over at another four weeks. 18F-FDG PET-CT brain scans acquired on the GE-Discovery 710 PET system (GE Healthcare, Chicago, IL) with 128-slice CT (250-MBq dose) were analyzed using the PMOD software (PMOD Technologies Ltd, Zurich, Switzerland). A total of 18 pain regions, the right and left prefrontal cortex (PFC), insula, anterior cingulate cortex (ACC), hippocampus, amygdala, primary somatosensory cortices, secondary somatosensory cortices (SSCII), thalami, parabrachial, and periaqueductal gray (PAG), were analyzed. RESULTS: A total of 14 patients received 40 Hz for four weeks before crossing over to 10,000 Hz/4000 Hz. A total of 57 PET-CT scans (15 for baseline and 14 each for 40 Hz, 4000 Hz, and 10,000 Hz) were analyzed for maximum standardized uptake value (SUVmax), with a statistically significant difference in SUVmax between 40 Hz and baseline (p = 0.002) and 4000 Hz and baseline (p = 0.001) when pooled across 18 pain matrices. There was no statistical difference in SUVmax between 10,000 Hz and baseline. The pooled analysis showed a proportionately higher thalamic region reduction (59.5%) in metabolic activity than other pain matrices, PFC (52%), insula (50%), ACC (52%), SSCII (49%), and PAG (52%). CONCLUSION: This large cohort of brain PET scans (n = 57) shows statistically significant differences in brain metabolic activity at 40 Hz and 4000 Hz from baseline, with effect on both nociceptive and affect-cognitive pathways (proportionately higher reduction in the thalamus), highlighting the possible mechanism of SCS. CLINICAL TRIAL REGISTRATION: The Clinicaltrials.gov registration number for the study is NCT03716557.

Potential impact of texture analysis in contrast enhanced CT in non-small cell lung cancer as a marker of survival: A retrospective feasibility study.

The objective of this feasibility study was to assess computed tomography (CT) texture analysis (CTTA) of pulmonary lesions as a predictor of overall survival in patients with suspected lung cancer on contrast-enhanced computed tomography (CECT). In a retrospective pilot study, 94 patients (52 men and 42 women; mean age, 67.2 ±â€…10.8 yrs) from 1 center with non-small cell lung cancer (NSCLC) underwent CTTA on the primary lesion by 2 individual readers. Both simple and multivariate Cox regression analyses correlating textural parameters with overall survival were performed. Statistically significant parameters were selected, and optimal cutoff values were determined. Kaplan-Meier plots based on these results were produced. Simple Cox regression analysis showed that normalized uniformity had a hazard ratio (HR) of 16.059 (3.861-66.788, P < .001), and skewness had an HR of 1.914 (1.330-2.754, P < .001). The optimal cutoff values for both parameters were 0.8602 and 0.1554, respectively. Normalized uniformity, clinical stage, and skewness were found to be prognostic factors for overall survival in multivariate analysis. Tumor heterogeneity, assessed by normalized uniformity and skewness on CECT may be a prognostic factor for overall survival.

Using texture analysis in the development of a potential radiomic signature for early identification of hepatic metastasis in colorectal cancer.

Background: Radiomics allows information not readily available to the naked eye to be extracted from high resolution imaging modalities such as CT. Identifying that a cancer has already metastasised at the time of presentation through a radiomic signature will affect the treatment pathway. The ability to recognise the existence of metastases earlier will have a significant impact on the survival outcomes. Aim: To create a novel radiomic signature using textural analysis in the evaluation of synchronous liver metastases in colorectal cancer. Methods: CT images at baseline and subsequent surveillance over a 5-year period of patients with colorectal cancer were processed using textural analysis software. Comparison was made between those patients who developed liver metastases and those that remained disease free to detect differences in the 'texture' of the liver. Results: A total of 24 patients were divided into two matched groups for comparison. Significant differences between the two groups scores when using the textural analysis programme were found on coarse filtration (p = 0.044). Patients that went on to develop metastases an average of 18 months after presentation had higher levels of hepatic heterogeneity on CT. Conclusion: This initial study demonstrates the potential of using a textural analysis programme to build a radiomic signature to predict the development of hepatic metastases in rectal cancer patients otherwise thought to have clear staging CT scans at time of presentation.

Filtration-histogram based texture analysis and CALIPER based pattern analysis as quantitative CT techniques in idiopathic pulmonary fibrosis: head-to-head comparison.

OBJECTIVE: To assess the prognostic performance of two quantitative CT (qCT) techniques in idiopathic pulmonary fibrosis (IPF) compared to established clinical measures of disease severity (GAP index). METHODS: Retrospective analysis of high-resolution CT scans for 59 patients (age 70.5 ± 8.8 years) with two qCT methods. Computer-aided lung informatics for pathology evaluation and ratings based analysis classified the lung parenchyma into six different patterns: normal, ground glass, reticulation, hyperlucent, honeycombing and pulmonary vessels. Filtration histogram-based texture analysis extracted texture features: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPPs), skewness and kurtosis at different spatial scale filters. Univariate Kaplan-Meier survival analysis assessed the different qCT parameters' performance to predict patient outcome and refine the standard GAP staging system. Multivariate cox regression analysis assessed the independence of the significant univariate predictors of patient outcome. RESULTS: The predominant parenchymal lung pattern was reticulation (16.6% ± 13.9), with pulmonary vessel percentage being the most predictive of worse patient outcome (p = 0.009). Higher SD, entropy and MPP, in addition to lower skewness and kurtosis at fine texture scale (SSF2), were the most significant predictors of worse outcome (p < 0.001). Multivariate cox regression analysis demonstrated that SD (SSF2) was the only independent predictor of survival (p < 0.001). Better patient outcome prediction was achieved after adding total vessel percentage and SD (SSF2) to the GAP staging system (p = 0.006). CONCLUSION: Filtration-histogram texture analysis can be an independent predictor of patient mortality in IPF patients. ADVANCES IN KNOWLEDGE: qCT analysis can help in risk stratifying IPF patients in addition to clinical markers.

Evolution of 18F-FDG PET/CT Findings in Patients After COVID-19: An Initial Investigation.

The aim of this study was to assess the temporal evolution of pulmonary 18F-FDG uptake in patients with coronavirus disease 2019 (COVID-19) and post-COVID-19 lung disease (PCLD). Methods: Using our hospital's clinical electronic records, we retrospectively identified 23 acute COVID-19, 18 PCLD, and 9 completely recovered 18F-FDG PET/CT patients during the 2 peaks of the U.K. pandemic. Pulmonary 18F-FDG uptake was measured as a lung target-to-background ratio (TBRlung = SUVmax/SUVmin) and compared with temporal stage. Results: In acute COVID-19, less than 3 wk after infection, TBRlung was strongly correlated with time after infection (rs = 0.81, P < 0.001) and was significantly higher in the late stage than in the early stage (P = 0.001). In PCLD, TBRlung was lower in patients treated with high-dose steroids (P = 0.003) and in asymptomatic patients (P < 0.001). Conclusion: Pulmonary 18F-FDG uptake in COVID-19 increases with time after infection. In PCLD, pulmonary 18F-FDG uptake rises despite viral clearance, suggesting ongoing inflammation. There was lower pulmonary 18F-FDG uptake in PCLD patients treated with steroids.

Effectiveness of high dose spinal cord stimulation for non-surgical intractable lumbar radiculopathy - HIDENS Study.

OBJECTIVES: Spinal cord stimulation (SCS) is being increasingly used in non-surgical intractable low back pain. This study was designed to evaluate the efficacy of high-dose (HD) SCS utilizing sub-perception stimulation with higher frequency and pulse width in non-surgical predominant low-back pain population at 12 months. MATERIALS AND METHODS: A total of 20 patients were recruited (280 screened between March 2017 and July 2018) to undergo percutaneous fluoroscopic-guided SCS (Medtronic 8 contact standard leads and RestoreR IPG), with T8 and T9 midline anatomical parallel placement. Sixteen patients completed 12 months follow-up (500 Hz frequency, 500 µs pulse width, and 25% pulse density). Differences in patients' clinical outcome (NRS back, NRS leg, ODI, PGIC, and PSQ) and medication usage (MQS) at 1, 3, and 12 months from the baseline were assessed using non-parametric Wilcoxon paired test. RESULTS: The mean NRS scores for back pain (baseline 7.53) improved significantly at 1, 3, and 12 months; 2.78 (p < 0.001), 4.45 (p = 0.002), and 3.85 (p = 0.002), respectively. The mean NRS score for leg pain (baseline 6.09) improved significantly at 1 and 3 months; 1.86 (p < 0.001) and 3.13 (p = 0.010), respectively. Mean NRS for leg pain at 12 months was 3.85 (p = 0.057). ODI and sleep demonstrated significant improvement as there was consistent improvement in medication particularly opioid usage (MQS) at 12 months. CONCLUSIONS: This study demonstrates that anatomical placement of leads with sub-perception HD stimulation could provide effective pain relief in patients who are not candidates for spinal surgery.

Response prediction of neoadjuvant chemoradiation therapy in locally advanced rectal cancer using CT-based fractal dimension analysis.

OBJECTIVES: There are individual variations in neo-adjuvant chemoradiation therapy (nCRT) in patients with locally advanced rectal cancer (LARC). No reliable modality currently exists that can predict the efficacy of nCRT. The purpose of this study is to assess if CT-based fractal dimension and filtration-histogram texture analysis can predict therapeutic response to nCRT in patients with LARC. METHODS: In this retrospective study, 215 patients (average age: 57 years (18-87 years)) who received nCRT for LARC between June 2005 and December 2016 and underwent a staging diagnostic portal venous phase CT were identified. The patients were randomly divided into two datasets: a training set (n = 170), and a validation set (n = 45). Tumor heterogeneity was assessed on the CT images using fractal dimension (FD) and filtration-histogram texture analysis. In the training set, the patients with pCR and non-pCR were compared in univariate analysis. Logistic regression analysis was applied to identify the predictive value of efficacy of nCRT and receiver operating characteristic analysis determined optimal cutoff value. Subsequently, the most significant parameter was assessed in the validation set. RESULTS: Out of the 215 patients evaluated, pCR was reached in 20.9% (n = 45/215) patients. In the training set, 7 out of 37 texture parameters showed significant difference comparing between the pCR and non-pCR groups and logistic multivariable regression analysis incorporating clinical and 7 texture parameters showed that only FD was associated with pCR (p = 0.001). The area under the curve of FD was 0.76. In the validation set, we applied FD for predicting pCR and sensitivity, specificity, and accuracy were 60%, 89%, and 82%, respectively. CONCLUSION: FD on pretreatment CT is a promising parameter for predicting pCR to nCRT in patients with LARC and could be used to help make treatment decisions. KEY POINTS: • Fractal dimension analysis on pretreatment CT was associated with response to neo-adjuvant chemoradiation in patients with locally advanced rectal cancer. • Fractal dimension is a promising biomarker for predicting pCR to nCRT and may potentially select patients for individualized therapy.

Exploring CT Texture Parameters as Predictive and Response Imaging Biomarkers of Survival in Patients With Metastatic Melanoma Treated With PD-1 Inhibitor Nivolumab: A Pilot Study Using a Delta-Radiomics Approach.

In the era of artificial intelligence and precision medicine, the use of quantitative imaging methodological approaches could improve the cancer patient's therapeutic approaches. Specifically, our pilot study aims to explore whether CT texture features on both baseline and first post-treatment contrast-enhanced CT may act as a predictor of overall survival (OS) and progression-free survival (PFS) in metastatic melanoma (MM) patients treated with the PD-1 inhibitor Nivolumab. Ninety-four lesions from 32 patients treated with Nivolumab were analyzed. Manual segmentation was performed using a free-hand polygon approach by drawing a region of interest (ROI) around each target lesion (up to five lesions were selected per patient according to RECIST 1.1). Filtration-histogram-based texture analysis was employed using a commercially available research software called TexRAD (Feedback Medical Ltd, London, UK; https://fbkmed.com/texrad-landing-2/) Percentage changes in texture features were calculated to perform delta-radiomics analysis. Texture feature kurtosis at fine and medium filter scale predicted OS and PFS. A higher kurtosis is correlated with good prognosis; kurtosis values greater than 1.11 for SSF = 2 and 1.20 for SSF = 3 were indicators of higher OS (fine texture: 192 HR = 0.56, 95% CI = 0.32-0.96, p = 0.03; medium texture: HR = 0.54, 95% CI = 0.29-0.99, p = 0.04) and PFS (fine texture: HR = 0.53, 95% CI = 0.29-0.95, p = 0.03; medium texture: HR = 0.49, 209 95% CI = 0.25-0.96, p = 0.03). In delta-radiomics analysis, the entropy percentage variation correlated with OS and PFS. Increasing entropy indicates a worse outcome. An entropy variation greater than 5% was an indicator of bad prognosis. CT delta-texture analysis quantified as entropy predicted OS and PFS. Baseline CT texture quantified as kurtosis also predicted survival baseline. Further studies with larger cohorts are mandatory to confirm these promising exploratory results.

Filtration-Histogram Based Magnetic Resonance Texture Analysis (MRTA) for the Distinction of Primary Central Nervous System Lymphoma and Glioblastoma.

Primary central nervous system lymphoma (PCNSL) has variable imaging appearances, which overlap with those of glioblastoma (GBM), thereby necessitating invasive tissue diagnosis. We aimed to investigate whether a rapid filtration histogram analysis of clinical MRI data supports the distinction of PCNSL from GBM. Ninety tumours (PCNSL n = 48, GBM n = 42) were analysed using pre-treatment MRI sequences (T1-weighted contrast-enhanced (T1CE), T2-weighted (T2), and apparent diffusion coefficient maps (ADC)). The segmentations were completed with proprietary texture analysis software (TexRAD version 3.3). Filtered (five filter sizes SSF = 2-6 mm) and unfiltered (SSF = 0) histogram parameters were compared using Mann-Whitney U non-parametric testing, with receiver operating characteristic (ROC) derived area under the curve (AUC) analysis for significant results. Across all (n = 90) tumours, the optimal algorithm performance was achieved using an unfiltered ADC mean and the mean of positive pixels (MPP), with a sensitivity of 83.8%, specificity of 8.9%, and AUC of 0.88. For subgroup analysis with >1/3 necrosis masses, ADC permitted the identification of PCNSL with a sensitivity of 96.9% and specificity of 100%. For T1CE-derived regions, the distinction was less accurate, with a sensitivity of 71.4%, specificity of 77.1%, and AUC of 0.779. A role may exist for cross-sectional texture analysis without complex machine learning models to differentiate PCNSL from GBM. ADC appears the most suitable sequence, especially for necrotic lesion distinction.

Radiomics-Based Texture Analysis of 68Ga-DOTATATE Positron Emission Tomography and Computed Tomography Images as a Prognostic Biomarker in Adults With Neuroendocrine Cancers Treated With 177Lu-DOTATATE.

PURPOSE: Neuroendocrine tumors (NET) are rare cancers with variable behavior. A better understanding of prognosis would aid individualized management. The aim of this hypothesis-generating pilot study was to investigate the prognostic potential of tumor heterogeneity and tracer avidity in NET using texture analysis (TA) of 68Ga-DOTATATE positron emission tomography (PET) and non-enhanced computed tomography (CT) performed at baseline in patients treated with 177Lu-DOTATATE. It aims to justify a larger-scale study to evaluate its clinical value. METHODS: The pretherapy 68Ga-DOTATATE PET-CT scans of 44 patients with metastatic NET (carcinoid, pancreatic, thyroid, head and neck, catecholamine-secreting, and unknown primary NET) treated with 177Lu-DOTATATE were analyzed retrospectively using commercially available texture analysis research software. Image filtration extracted and enhanced objects of different sizes (fine, medium, coarse), then quantified heterogeneity by statistical and histogram-based parameters (mean intensity, standard deviation, entropy, mean of positive pixels, skewness, and kurtosis). Regions of interest were manually drawn around up to five of the most 68Ga-DOTATATE avid lesions for each patient. 68Gallium uptake on PET was quantified as SUVmax and SUVmean. Associations between imaging and clinical markers with progression-free (PFS) and overall survival (OS) were assessed using univariate Kaplan-Meier analysis. Independence of the significant univariate markers of survival was tested using multivariate Cox regression analysis. RESULTS: Measures of heterogeneity (higher kurtosis, higher entropy, and lower skewness) on coarse-texture scale CT and unfiltered PET images predicted shorter PFS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness: p=0.03) and shorter OS (CT coarse kurtosis: p=0.05, PET entropy: p=0.01, PET skewness p=0.02). Conventional PET parameters such as SUVmax and SUVmean showed trends towards predicting outcome but were not statistically significant. Multivariate analysis identified that CT-TA (coarse kurtosis: HR=2.57, 95% CI=1.22-5.38, p=0.013) independently predicted PFS, and PET-TA (unfiltered skewness: HR=9.05, 95% CI=1.19-68.91, p=0.033) independently predicted OS. CONCLUSION: These preliminary data generate a hypothesis that radiomic analysis of neuroendocrine cancer on 68Ga-DOTATATE PET-CT may be of prognostic value and a valuable addition to the assessment of patients.

Chest CT texture-based radiomics analysis in differentiating COVID-19 from other interstitial pneumonia.

PURPOSE: To evaluate the potential role of texture-based radiomics analysis in differentiating Coronavirus Disease-19 (COVID-19) pneumonia from pneumonia of other etiology on Chest CT. MATERIALS AND METHODS: One hundred and twenty consecutive patients admitted to Emergency Department, from March 8, 2020, to April 25, 2020, with suspicious of COVID-19 that underwent Chest CT, were retrospectively analyzed. All patients presented CT findings indicative for interstitial pneumonia. Sixty patients with positive COVID-19 real-time reverse transcription polymerase chain reaction (RT-PCR) and 60 patients with negative COVID-19 RT-PCR were enrolled. CT texture analysis (CTTA) was manually performed using dedicated software by two radiologists in consensus and textural features on filtered and unfiltered images were extracted as follows: mean intensity, standard deviation (SD), entropy, mean of positive pixels (MPP), skewness, and kurtosis. Nonparametric Mann-Whitney test assessed CTTA ability to differentiate positive from negative COVID-19 patients. Diagnostic criteria were obtained from receiver operating characteristic (ROC) curves. RESULTS: Unfiltered CTTA showed lower values of mean intensity, MPP, and kurtosis in COVID-19 positive patients compared to negative patients (p = 0.041, 0.004, and 0.002, respectively). On filtered images, fine and medium texture scales were significant differentiators; fine texture scale being most significant where COVID-19 positive patients had lower SD (p = 0.004) and MPP (p = 0.004) compared to COVID-19 negative patients. A combination of the significant texture features could identify the patients with positive COVID-19 from negative COVID-19 with a sensitivity of 60% and specificity of 80% (p = 0.001). CONCLUSIONS: Preliminary evaluation suggests potential role of CTTA in distinguishing COVID-19 pneumonia from other interstitial pneumonia on Chest CT.

Prediction of Inflammatory Breast Cancer Survival Outcomes Using Computed Tomography-Based Texture Analysis.

Background: Although inflammatory breast cancer (IBC) has poor overall survival (OS), there is little information about using imaging features for predicting the prognosis. Computed tomography (CT)-based texture analysis, a non-invasive technique to quantify tumor heterogeneity, could be a potentially useful imaging biomarker. The aim of the article was to investigate the usefulness of chest CT-based texture analysis to predict OS in IBC patients. Methods: Of the 3,130 patients with primary breast cancers between 2006 and 2016, 104 patients (3.3%) with IBC were identified. Among them, 98 patients who underwent pre-treatment contrast-enhanced chest CT scans, got treatment in our institution, and had a follow-up period of more than 2 years were finally included for CT-based texture analysis. Texture analysis was performed on CT images of 98 patients, using commercially available software by two breast radiologists. Histogram-based textural features, such as quantification of variation in CT attenuation (mean, standard deviation, mean of positive pixels [MPP], entropy, skewness, and kurtosis), were recorded. To dichotomize textural features for survival analysis, receiver operating characteristic curve analysis was used to determine cutoff points. Clinicopathologic variables, such as age, node stage, metastasis stage at the time of diagnosis, hormonal receptor positivity, human epidermal growth factor receptor 2 positivity, and molecular subtype, were assessed. A Cox proportional hazards model was used to determine the association of textural features and clinicopathologic variables with OS. Results: During a mean follow-up period of 47.9 months, 41 of 98 patients (41.8%) died, with a median OS of 20.0 months. The textural features of lower mean attenuation, standard deviation, MPP, and entropy on CT images were significantly associated with worse OS, as was the M1 stage among clinicopathologic variables (all P-values < 0.05). In multivariate analysis, lower mean attenuation (hazard ratio [HR], 3.26; P = 0.003), lower MPP (HR, 3.03; P = 0.002), and lower entropy (HR, 2.70; P = 0.009) on chest CT images were significant factors independent from the M1 stage for predicting worse OS. Conclusions: Lower mean attenuation, MPP, and entropy on chest CT images predicted worse OS in patients with IBC, suggesting that CT-based texture analysis provides additional predictors for OS.

Texture Analysis of Fractional Water Content Images Acquired during PET/MRI: Initial Evidence for an Association with Total Lesion Glycolysis, Survival and Gene Mutation Profile in Primary Colorectal Cancer.

To assess the capability of fractional water content (FWC) texture analysis (TA) to generate biologically relevant information from routine PET/MRI acquisitions for colorectal cancer (CRC) patients. Thirty consecutive primary CRC patients (mean age 63.9, range 42-83 years) prospectively underwent FDG-PET/MRI. FWC tumor parametric images generated from Dixon MR sequences underwent TA using commercially available research software (TexRAD). Data analysis comprised (1) identification of functional imaging correlates for texture features (TF) with low inter-observer variability (intraclass correlation coefficient: ICC > 0.75), (2) evaluation of prognostic performance for FWC-TF, and (3) correlation of prognostic imaging signatures with gene mutation (GM) profile. Of 32 FWC-TF with ICC > 0.75, 18 correlated with total lesion glycolysis (TLG, highest: rs = -0.547, p = 0.002). Using optimized cut-off values, five MR FWC-TF identified a good prognostic group with zero mortality (lowest: p = 0.017). For the most statistically significant prognostic marker, favorable prognosis was significantly associated with a higher number of GM per patient (medians: 7 vs. 1.5, p = 0.009). FWC-TA derived from routine PET/MRI Dixon acquisitions shows good inter-operator agreement, generates biological relevant information related to TLG, GM count, and provides prognostic information that can unlock new clinical applications for CRC patients.

FDG-PET/CT in colorectal cancer: potential for vascular-metabolic imaging to provide markers of prognosis.

PURPOSE: This study assesses the potential for vascular-metabolic imaging with FluoroDeoxyGlucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) perfusion to provide markers of prognosis specific to the site and stage of colorectal cancer. METHODS: This prospective observational study comprised of participants with suspected colorectal cancer categorized as either (a) non-metastatic colon cancer (M0colon), (b) non-metastatic rectal cancer (M0rectum), or (c) metastatic colorectal cancer (M+). Combined FDG-PET/CT perfusion imaging was successfully performed in 286 participants (184 males, 102 females, age: 69.60 ± 10 years) deriving vascular and metabolic imaging parameters. Vascular and metabolic imaging parameters alone and in combination were investigated with respect to overall survival. RESULTS: A vascular-metabolic signature that was significantly associated with poorer survival was identified for each patient group: M0colon - high Total Lesion Glycolysis (TLG) with increased Permeability Surface Area Product/Blood Flow (PS/BF), Hazard Ratio (HR) 3.472 (95% CI: 1.441-8.333), p = 0.006; M0rectum - high Metabolic Tumour Volume (MTV) with increased PS/BF, HR 4.567 (95% CI: 1.901-10.970), p = 0.001; M+ participants, high MTV with longer Time To Peak (TTP) enhancement, HR 2.421 (95% CI: 1.162-5.045), p = 0.018. In participants with stage 2 colon cancer as well as those with stage 3 rectal cancer, the vascular-metabolic signature could stratify the prognosis of these participants. CONCLUSION: Vascular and metabolic imaging using FDG-PET/CT can be used to synergise prognostic markers. The hazard ratios suggest that the technique may have clinical utility.