Penalized deep partially linear cox models with application to CT scans of lung cancer patients.

Lung cancer is a leading cause of cancer mortality globally, highlighting the importance of understanding its mortality risks to design effective patient-centered therapies. The National Lung Screening Trial (NLST) employed computed tomography texture analysis, which provides objective measurements of texture patterns on CT scans, to quantify the mortality risks of lung cancer patients. Partially linear Cox models have gained popularity for survival analysis by dissecting the hazard function into parametric and nonparametric components, allowing for the effective incorporation of both well-established risk factors (such as age and clinical variables) and emerging risk factors (eg, image features) within a unified framework. However, when the dimension of parametric components exceeds the sample size, the task of model fitting becomes formidable, while nonparametric modeling grapples with the curse of dimensionality. We propose a novel Penalized Deep Partially Linear Cox Model (Penalized DPLC), which incorporates the smoothly clipped absolute deviation (SCAD) penalty to select important texture features and employs a deep neural network to estimate the nonparametric component of the model. We prove the convergence and asymptotic properties of the estimator and compare it to other methods through extensive simulation studies, evaluating its performance in risk prediction and feature selection. The proposed method is applied to the NLST study dataset to uncover the effects of key clinical and imaging risk factors on patients' survival. Our findings provide valuable insights into the relationship between these factors and survival outcomes.

A nomogram based on CT texture features to predict the response of patients with advanced pancreatic cancer treated with chemotherapy.

OBJECTIVE: This study aimed to evaluate the predictive value of computed tomography (CT) texture features in the treatment response of patients with advanced pancreatic cancer (APC) receiving palliative chemotherapy. METHODS: This study enrolled 84 patients with APC treated with first-line chemotherapy and conducted texture analysis on primary pancreatic tumors. 59 patients and 25 were randomly assigned to the training and validation cohorts at a ratio of 7:3. The treatment response to chemotherapy was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST1.1). The patients were divided into progressive and non-progressive groups. The least absolute shrinkage selection operator (LASSO) was applied for feature selection in the training cohort and a radiomics signature (RS) was calculated. A nomogram was developed based on a multivariate logistic regression model incorporating the RS and carbohydrate antigen 19-9 (CA19-9), and was internally validated using the C-index and calibration plot. We performed the decision curve analysis (DCA) and clinical impact curve analysis to reflect the clinical utility of the nomogram. The nomogram was further externally confirmed in the validation cohort. RESULTS: The multivariate logistic regression analysis indicated that the RS and CA19-9 were independent predictors (P < 0.05), and a trend was found for chemotherapy between progressive and non-progressive groups. The nomogram incorporating RS, CA19-9 and chemotherapy showed favorable discriminative ability in the training (C-index = 0.802) and validation (C-index = 0.920) cohorts. The nomogram demonstrated favorable clinical utility. CONCLUSION: The RS of significant texture features was significantly associated with the early treatment effect of patients with APC treated with chemotherapy. Based on the RS, CA19-9 and chemotherapy, the nomogram provided a promising way to predict chemotherapeutic effects for APC patients.

Machine learning-based CT texture analysis in the differentiation of testicular masses.

Purpose: To evaluate the ability of texture features for distinguishing between benign and malignant testicular masses, and furthermore, for identifying primary testicular lymphoma in malignant tumors and identifying seminoma in testicular germ cell tumors, respectively. Methods: We retrospectively collected 77 patients with an abdominal and pelvic enhanced computed tomography (CT) examination and a histopathologically confirmed testicular mass from a single center. The ROI of each mass was split into two parts by the largest cross-sectional slice and deemed to be two samples. After all processing steps, three-dimensional texture features were extracted from unenhanced and contrast-enhanced CT images. Excellent reproducibility of texture features was defined as intra-class correlation coefficient ≥0.8 (ICC ≥0.8). All the groups were balanced via the synthetic minority over-sampling technique (SMOTE) method. Dimension reduction was based on pearson correlation coefficient (PCC). Before model building, minimum-redundancy maximum-relevance (mRMR) selection and recursive feature elimination (RFE) were used for further feature selection. At last, three ML classifiers with the highest cross validation with 5-fold were selected: autoencoder (AE), support vector machine(SVM), linear discriminant analysis (LAD). Logistics regression (LR) and LR-LASSO were also constructed to compare with the ML classifiers. Results: 985 texture features with ICC ≥0.8 were extracted for further feature selection process. With the highest AUC of 0.946 (P <0.01), logistics regression was proved to be the best model for the identification of benign or malignant testicular masses. Besides, LR also had the best performance in identifying primary testicular lymphoma in malignant testicular tumors and in identifying seminoma in testicular germ cell tumors, with the AUC of 0.982 (P <0.01) and 0.928 (P <0.01), respectively. Conclusion: Until now, this is the first study that applied CT texture analysis (CTTA) to assess the heterogeneity of testicular tumors. LR model based on CTTA might be a promising non-invasive tool for the diagnosis and differentiation of testicular masses. The accurate diagnosis of testicular masses would assist urologists in correct preoperative and perioperative decision making.

Correlation of CT-data derived from multiparametric dual-layer CT-maps with immunohistochemical biomarkers in invasive breast carcinomas.

OBJECTIVE: To examine the correlation of quantitative measurements from material decomposition maps calculated from dual-layer CT (DLCT)-image datasets with immunohistochemical biomarkers of invasive breast carcinomas. MATERIAL AND METHODS: All patients at the University Breast Cancer Center who underwent a clinically indicated dual-layer CT-scan for staging of invasive ductal breast carcinoma from 01/2016 to 07/2020 were prospectively included. Iodine concentration maps and maps of the effective atomic numbers (Zeffective) were reconstructed from the image datasets. ROI-based evaluations of the index tumors and predefined references tissues for normalization were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Statistical analysis was essentially descriptive using Spearmans rank correlation and (multivariable) partial correlation. RESULTS: Bivariate showed statistically significant correlations of iodine contents (r = -0.154/-0.202/0.180, p = 0.039/0.006/0.015), and Zeffective-values (r = -0.158/-0.199/0.179, p = 0.034/0.007/0.016) for all 184 carcinomas and the subgroup of 168 invasive ductal carcinomas. The results were confirmed by multivariate analyses with "age", "diameter" and "ACR-grade" as possible confounders. Normalization of the measured target values with those in the aorta confirmed significant correlations of iodine content and Zeffective compared to Estrogen (r = 0.174, p = 0.019), Progesteron (r = 0.168/0.177, p = 0.024/0.017), and HER2 receptor expression (r = -0.222/-0.184, p = 0.003/0.013). All CT-parameters showed significant correlations with immunohistochemical subtyping (r = 0.191/0.192, p = 0.010). CONCLUSIONS: Our preliminary results indicate that iodine content and Zeffective-values derived from DLCT-examinations correlate with hormone receptor expression in invasive breast carcinomas. Assignments to benign entities already seam feasible in clinical routine CT-diagnostics. After further investigations iodine content and Zeffective may be translated as diagnostical and prognostical biomarkers into clinical routine in the long term.

Radiomics and functional imaging in lung cancer: the importance of radiological heterogeneity beyond FDG PET/CT and lung biopsy.

PURPOSE: [18F]-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (FDG PET/CT) has a central role in the lung nodules' characterization even if, with SUV < 2.5, percutaneous CT-guided Lung Biopsy (CTLB) is needed to assess nodule nature. In that scenario, CT Texture Analysis (CTTA) could be a non-invasive imaging biomarker. Our purpose is to test CTTA ability in differentiating malignant from benign nodules. METHOD: Patients that underwent FDG PET/CT followed by CTLB between January 2013 and December 2018 were retrospectively enrolled. Were included patients with lung nodule SUV < 2.5 and histological diagnosis. EXCLUSION CRITERIA: nodules SUV > 2.5, patients who refused CTLB or received oncological treatment before CTLB, indeterminate pathology report, CT motion artifacts. Two radiologists in consensus performed CTTA, drawing a volumetric Region of Interest of nodule with a dedicated first order TA software with and without spatial scaling filters, on preliminary CT performed for CTLB. Statistics included a comparison between malignant and benign neoplasms distribution (2-tailed T-test or Mann-Whitney test according to normal/non-normal data distribution), P-values < 0.05 were considered statistically significant. CTTA accuracy was tested with Receiver Operating Characteristics (ROC) curve. RESULTS: Form an initial population of 1178, 46 patients encountered inclusion criteria. Pathologist reported 27/46 (59%) malignant and 19/46 (41%) benign nodules. In malignant lesions CTTA showed lower Kurtosis' and higher Skewness' values (all P ≤ 0.0013 and all filtered TA P < 0.024, respectively). ROC curve showed significant Area Under the Curve for Kurtosis and Skewness (0.654 and 0.642, P < 0.001) at medium filtration. CONCLUSIONS: CTTA is a promising radiological tool to characterize benign and malignant lung nodules, even in those cases without an altered glucose metabolism.

CT radiomic features of photodynamic priming in clinical pancreatic adenocarcinoma treatment.

Photodynamic therapy (PDT) offers localized focal ablation in unresectable pancreatic tumors while tissues surrounding the treatment volume experience a lower light dose, termed photodynamic priming (PDP). While PDP does not cause tissue damage, it has been demonstrated to promote vascular permeability, improve drug delivery, alleviate tumor cell density, and reduce desmoplasia and the resultant internal pressure in pre-clinical evaluation. Preclinical data supports PDP as a neoadjuvant therapy beneficial to subsequent chemotherapy or immunotherapy, yet it is challenging to quantify PDP effects in clinical treatment without additional imaging and testing. This study investigated the potential of radiomic analysis using CT scans acquired before and after PDT to identify areas experiencing PDT-induced necrosis as well as quantify PDP effects in the surrounding tissues. A total of 235 CT tumor slices from seven patients undergoing PDT for pancreatic tumors were examined. Radiomic features assessed included intensity metrics (CT number in Hounsfield Units) and texture analysis using several gray-level co-occurrence matrix (GLCM) parameters. Pre-treatment scans of tumor areas that resulted in PDT-induced necrosis showed statistically significant differences in intensity and texture-based features that could be used to predict the regions that did respond (paired t-test, response versus no response,p < 0.001). Evaluation of PDP effects on the surrounding tissues also demonstrated statistically significant differences, in tumor mean value, standard deviation, and GLCM parameters of contrast, dissimilarity and homogeneity (t-test, pre versus post,p < 0.001). Using leave-one-out cross validation, six intensity and texture-based features were combined into a support-vector machine model which demonstrated reliable prediction of treatment effects for six out of seven patients (ROC curve, AUC = 0.93). This study provides pilot evidence that texture features extracted from CT scans could be utilized as an effective clinical diagnostic prediction and assessment of PDT and PDP effects in pancreatic tumors. (clinical trial NCT03033225).

Prediction of the early recurrence in spinal giant cell tumor of bone using radiomics of preoperative CT: Long-term outcome of 62 consecutive patients.

OBJECTIVES: To determine if radiomics analysis based on preoperative computed tomography (CT) can predict early postoperative recurrence of giant cell tumor of bone (GCTB) in the spine. METHODS: In a retrospective review, 62 patients with pathologically confirmed spinal GCTB from March 2008 to February 2018, with a minimum follow-up of 24 months, were identified. The mean follow-up was 73.7 months (range, 28.7-152.1 months). The clinical information including age, gender, lesion location, multi-vertebral involvement, and surgical methods, were obtained. CT images acquired before the operation were retrieved for radiomics analysis. For each case, the tumor regions of interest (ROI) was manually outlined, and a total of 107 radiomics features were extracted. The features were selected via the sequential selection process by using the support vector machine (SVM), then used to construct classification models with Gaussian kernels. The differentiation between recurrence and non-recurrence groups was evaluated by ROC analysis, using 10-fold cross-validation. RESULTS: Of the 62 patients, 17 had recurrence with a recurrence rate of 27.4%. None of the clinical information was significantly different between the two groups. Patients receiving curettage had a higher recurrence rate (6/16 = 37.5%) compared to patients receiving TES (6/26 = 23.1%) or intralesional spondylectomy (5/20 = 25%). The final radiomics model was built using 10 selected features, which achieved an accuracy of 89% with AUC of 0.78. CONCLUSIONS: The radiomics model developed based on pre-operative CT can achieve a high accuracy to predict the recurrence of spinal GCTB. Patients who have a high risk of early recurrence should be treated more aggressively to minimize recurrence.

Role of CT texture features for predicting outcome of pancreatic cancer patients with liver metastases.

Objective: The purpose of this study was to evaluate the prognostic value of computed tomography (CT) texture features of pancreatic cancer with liver metastases. Methods: We included 39 patients with metastatic pancreatic cancer (MPC) with liver metastases and performed texture analysis on primary tumors and metastases. The correlations between texture parameters were assessed using Pearson's correlation. Univariate Cox proportional hazards model was used to assess the correlations between clinicopathological characteristics, texture features and overall survival (OS). The univariate Cox regression model revealed four texture features potentially correlated with OS (P<0.1). A radiomics score (RS) was determined using a sequential combination of four texture features with potential prognostic value that were weighted according to their ß-coefficients. Furthermore, all variables with P<0.1 were included in the multivariate analysis. A nomogram,which was developed to predict OS according to independent prognostic factors, was internally validated using the C-index and calibration plots. Kaplan-Meier analysis and the log-rank test were performed to stratify OS according to the RS and nomogram total points (NTP). Results: Few significant correlations were found between texture features of primary tumors and those of liver metastases. However, texture features within primary tumors or liver metastases were significantly associated. Multivariate analysis showed that Eastern Cooperative Oncology Group performance status (ECOG PS), chemotherapy, Carbohydrate antigen 19-9 (CA19-9), and the RS were independent prognostic factors (P<0.05). The nomogram incorporating these factors showed good discriminative ability (C-index = 0.754). RS and NTP stratified patients into two potential risk groups (P<0.01). Conclusion: The RS derived from significant texture features of primary tumors and metastases shows promise as a prognostic biomarker of OS of patients with MPC. A nomogram based on the RS and other independent prognostic clinicopathological factors accurately predicts OS.

Computed tomography texture-based radiomics analysis in gallbladder cancer: initial experience.

Aim of the study: To investigate computed tomography (CT) texture parameters in suspected gallbladder cancer (GBC) and assess its utility in predicting histopathological grade and overall survival. Material and methods: This retrospective pilot study included consecutive patients with clinically suspected GBC. CT images, clinical, and histological or cytological data were retrieved from the database. CT images were reviewed by two radiologists. A single axial CT section in the portal venous phase was selected for texture analysis. Radiomic feature extraction was done using commercially available research software. Results: Thirty-eight patients (31 females, mean age 53.1 years) were included. Malignancy was confirmed in 29 patients in histopathology or cytology analysis, and the rest had no features of malignancy. Exophytic gallbladder mass with associated gallbladder wall thickening was present in 22 (58%) patients. Lymph nodal, liver, and omental metastases were present in 10, 1, and 3 patients, respectively. The mean overall survival was 9.7 months. There were significant differences in mean and kurtosis at medium texture scales to differentiate moderately differentiated and poorly differentiated adenocarcinoma (p < 0.05). The only texture parameter that was significantly associated with survival was kurtosis (p = 0.020) at medium texture scales. In multivariate analysis, factors found to be significantly associated with length of overall survival were mean number of positive pixels (p = 0.02), skewness (p = -0.046), kurtosis (0.018), and standard deviation (p = 0.045). Conclusions: Our preliminary results highlight the potential utility of CT texture-based radiomics analysis in patients with GBC. Medium texture scale parameters including both mean and kurtosis, or kurtosis alone, may help predict the histological grade and survival, respectively.

A radiomics nomogram for the prediction of overall survival in patients with hepatocellular carcinoma after hepatectomy.

BACKGROUND: Hepatocellular carcinoma (HCC) is associated with a dismal prognosis, and prediction of the prognosis of HCC can assist in therapeutic decision-makings. An increasing number of studies have shown that the texture parameters of images can reflect the heterogeneity of tumors, and may have the potential to predict the prognosis of patients with HCC after surgical resection. The aim of this study was to investigate the prognostic value of computed tomography (CT) texture parameters in patients with HCC after hepatectomy and to develop a radiomics nomogram by combining clinicopathological factors and the radiomics signature. METHODS: In all, 544 eligible patients were enrolled in this retrospective study and were randomly divided into the training cohort (n = 381) and the validation cohort (n = 163). The tumor regions of interest (ROIs) were delineated, and the corresponding texture parameters were extracted. The texture parameters were selected by using the least absolute shrinkage and selection operator (LASSO) Cox model in the training cohort, and a radiomics signature was established. Then, the radiomics signature was further validated as an independent risk factor for overall survival (OS). The radiomics nomogram was established based on the Cox regression model. The concordance index (C-index), calibration plot and decision curve analysis (DCA) were used to evaluate the performance of the radiomics nomogram. RESULTS: The radiomics signature was formulated based on 7 OS-related texture parameters, which were selected in the training cohort. In addition, the radiomics nomogram was developed based on the following five variables: α-fetoprotein (AFP), platelet-to-lymphocyte ratio (PLR), largest tumor size, microvascular invasion (MVI) and radiomics score (Rad-score). The nomogram displayed good accuracy in predicting OS (C-index = 0.747) in the training cohort and was confirmed in the validation cohort (C-index = 0.777). The calibration plots also showed excellent agreement between the actual and predicted survival probabilities. The DCA indicated that the radiomics nomogram showed better clinical utility than the clinicopathologic nomogram. CONCLUSION: The radiomics signature is a potential prognostic biomarker of HCC after hepatectomy. The radiomics nomogram that integrated the radiomics signature can provide a more accurate estimation of OS than the clinicopathologic nomogram for HCC patients after hepatectomy.

CT texture analysis compared to Positron Emission Tomography (PET) and mutational status in resected melanoma metastases.

PURPOSE: To evaluate the potential of CT texture analysis parameters and metabolic characteristics of melanoma metastases in 18F- FDG PET/CT to predict relevant mutations of tumour cells for targeted therapy in metastatic melanoma patients in correlation with histopathologic specimen. MATERIAL AND METHODS: 66 melanoma patients, examined with contrast-enhanced 18F-FDG PET/CT before scheduled metastasectomy without any prior systemic therapy, were included in this single-centre retrospective analysis under IRB waiver. The largest, resected metastasis in each patient was assessed with CT texture analysis and semiquantitative 18F-FDG PET parameters. Correlation between imaging parameters and histopathological mutations (BRAF- and NRAS- genes) were calculated. RESULTS: Attenuation standard deviation (SD) within target lesion indicated a weak correlation with its SUVpeak (rho -0.292, p 0.017). However, no correlation between CT texture analysis, metabolic 18F-FDG PET parameters and tumour cell mutation could be established. CONCLUSION: CT texture parameters cannot replace the diagnostic value of 18F- FDG PET/CT for metabolic information in melanoma patients. Discrimination between BRAF- and NRAS mutation status was not feasible with CT texture analysis in this exploratory study.

Radiotranscriptomics signature-based predictive nomograms for radiotherapy response in patients with nonsmall cell lung cancer: Combination and association of CT features and serum miRNAs levels.

PURPOSE: We aimed to establish radiotranscriptomics signatures based on serum miRNA levels and computed tomography (CT) texture features and develop nomogram models for predicting radiotherapy response in patients with nonsmall cell lung cancer (NSCLC). METHODS: We first used established radioresistant NSCLC cell lines for miRNA selection. At the same time, patients (103 for training set and 71 for validation set) with NSCLC were enrolled. Their pretreatment contrast-enhanced CT texture features were extracted and their serum miRNA levels were obtained. Then, radiotranscriptomics feature selection was implemented with the least absolute shrinkage and selection operator (LASSO), and signatures were generated by logistic or Cox regression for objective response rate (ORR), overall survival (OS), and progression-free survival (PFS). Afterward, radiotranscriptomics signature-based nomograms were constructed and assessed for clinical use. RESULTS: Four miRNAs and 22 reproducible contrast-enhanced CT features were used for radiotranscriptomics feature selection and we generated ORR-, OS-, and PFS- related radiotranscriptomics signatures. In patients with NSCLC who received radiotherapy, the radiotranscriptomics signatures were independently associated with ORR, OS, and PFS in both the training (OR: 2.94, P < .001; HR: 2.90, P < .001; HR: 3.58, P = .001) and validation set (OR: 2.94, P = .026; HR: 2.14, P = .004; HR: 2.64, P = .016). We also obtained a satisfactory nomogram for ORR. The C-index values for the ORR nomogram were 0.86 [95% confidence interval (CI), 0.75 to 0.92] in the training set and 0.81 (95% CI, 0.69 to 0.89) in the validation set. The calibration-in-the-large and calibration slope performed well. Decision curve analysis indicated a satisfactory net benefit. CONCLUSIONS: The radiotranscriptomics signature could be an independent biomarker for evaluating radiotherapeutic responses in patients with NSCLC. The radiotranscriptomics signature-based nomogram could be used to predict patients' ORR, which would represent progress in individualized medicine.

CT texture analysis of liver metastases in PNETs versus NPNETs: Correlation with histopathological findings.

PURPOSE: To compare CT and Texture features of liver metastases in Pancreatic Neuroendocrine Tumors (PNETs) and in Non-Pancreatic Neuroendocrine Tumors (NPNETs) according to tumor grading, overall survival (OS), time to progression (TTP) and Ki67 index. METHODS: 23 patients with PNETs and 25 patients with NPNETs affected by liver metastases were compared. The lesions were G1 and G2 according to WHO classification of tumors. Texture parameters (Mean, Standard Deviation, Entropy, Kurtosis, Skewness, Mean of Positive Pixel) at different spatial scale image filtration (SSF) were evaluated in both arterial and portal phase using a dedicated software for volumetric analysis. All CT images were acquired before the beginning of any medical treatment. RESULTS: The following significant results (P < 0.05) were found: in the arterial phase for value of Skewness between PNETs G2 and NPNETs G2; in the portal phase between PNETs versus NPNETs, PNETs G1 versus NPNETs G1, PNETs G2 versus NPNETs G2; value of Mean in portal phase in PNETs vs NPNETs. Regarding PNETs, a P < 0.05 was found in: inverse correlation between Entropy and TTP; direct correlation between Mean and OS; correlating Kurtosis and high risk of death; correlating Skewness and low risk of death. Regarding NPNETs, P < 0.05 was found in: inverse correlation between Entropy and OS; correlating Entropy and high risk of dying. CONCLUSIONS: This study shows that CT texture features are significantly different in PNETs from NPNETs. Additionally, textural features such as Entropy, Kurtosis and Skewness, were found to have significant correlation with higher mortality risk.

[Correlation between CT Texture Analysis and Synchronous Distant Metastasis in Patients with Lymph Node-negative Colorectal Cancer].

Objective To investigate the correlation between CT texture analysis and synchronous distant metastasis in patients with lymph node-negative colorectal cancer. Methods The preoperative CT images of 82 patients with lymph node-negative colorectal cancer were analyzed retrospectively.There were 12 patients with simultaneous distant metastasis and 70 patients without simultaneous distant metastasis.The maximum plane of the lesion on plain scan and portal CT images was analyzed by TexRAD software.When the spatial scaling factor(SSF)was 0 and 2-6,six texture parameters were obtained,and the differences of texture parameters between the two groups were compared.The counting data were analyzed by chi-square test and the measurement data by Mann-Whitney test. Results There was a significant difference in the skewness of SSF=3 between the simultaneous distant metastasis group and the non-synchronous metastasis group on plain CT scan(P=0.031).On contrast-enhanced CT images,the entropy values of SSF=2,3,5,and 6 were statistically significant(P=0.048,P=0.027,P=0.016,P=0.017),and the peak values of SSF=2 were statistically significant(P=0.026).According to the comprehensive analysis of the texture parameters of the six groups,when the boundary value was 0.636,the sensitivity and specificity for the diagnosis of simultaneous distant metastasis were 75% and 89%,respectively. Conclusion CT texture analysis is useful in the diagnosis of synchronous distant metastasis in patients with lymph node-negative colorectal cancer.

CT texture analysis for the prediction of KRAS mutation status in colorectal cancer via a machine learning approach.

PURPOSE: This study aimed to investigate whether a machine learning-based computed tomography (CT) texture analysis could predict the mutation status of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) in colorectal cancer. METHOD: This retrospective study comprised 40 patients with pathologically confirmed colorectal cancer who underwent KRAS mutation testing, contrast-enhancement CT, and 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) before treatment. Of the 40 patients, 20 had mutated KRAS genes, whereas 20 had wild-type KRAS genes. Fourteen CT texture parameters were extracted from portal venous phase CT images of primary tumors, and the maximum standard uptake values (SUVmax) on 18F-FDG PET images were recorded. Univariate logistic regression was used to develop predictive models for each CT texture parameter and SUVmax, and a machine learning method (multivariate support vector machine) was used to develop a comprehensive set of CT texture parameters. The area under the receiver operating characteristic (ROC) curve (AUC) of each model was calculated using five-fold cross validation. In addition, the performance of the machine learning method with the CT texture parameters was compared with that of SUVmax. RESULTS: In the univariate analyses, the AUC of each CT texture parameter ranged from 0.4 to 0.7, while the AUC of the SUVmax was 0.58. Comparatively, the multivariate support vector machine with comprehensive CT texture parameters yielded an AUC of 0.82, indicating a superior prediction performance when compared to the SUVmax. CONCLUSIONS: A machine learning-based CT texture analysis was superior to the SUVmax for predicting the KRAS mutation status of a colorectal cancer.

Utility of CT Texture Analysis in Differentiating Low-Attenuation Renal Cell Carcinoma From Cysts: A Bi-Institutional Retrospective Study.

OBJECTIVE. The purpose of this study was to evaluate the utility of CT texture analysis (CTTA) in differentiating low-attenuation renal cell carcinoma (RCC) from renal cysts on unenhanced CT. MATERIALS AND METHODS. Ninety-four patients with low-attenuation RCC on unenhanced CT were compared with a cohort of 192 patients with benign renal cysts. CT characteristics (size and minimum, maximum, and mean attenuation) and CTTA features were recorded using an ROI approximately two-thirds the size of the mass. Masses were subjectively assessed by two expert genitourinary readers and two novice readers using a 5-point Likert scale (1 = definite cyst, 5 = definite renal cell carcinoma). Results of first-order CTTA and subjective evaluation were compared using ROC analysis. RESULTS. The group of 94 patients with low-attenuation RCC included 62 men and 32 women (mean age, 58.0 years). On unenhanced CT, the RCC were larger than 10 mm and of a median size of 50 mm with less than or equal to 20 HU (mean attenuation, 16 ± 4 HU). Of the RCC cohort, 83 were clear cell subtype. The cohort of 192 patients included 134 men and 58 women (mean age, 64.7 years) with benign renal cysts greater than 10 mm and a median size of 27 mm and less than or equal to 20 HU (mean attenuation, 9 ± 6 HU). The mean follow-up time was 6.2 years. Mean entropy in the low-attenuation RCC group (4.1 ± 0.7) was significantly higher than in the cyst group (2.8 ± 1.3, p < 0.0001). Entropy showed an ROC AUC of 0.89, with sensitivity of 84% and specificity of 80% at threshold 3.9. The AUC was better than subjective evaluation by novice readers (AUC, 0.77) and comparable to subjective evaluation by two expert readers (AUC, 0.90). A model combining the three best texture features (unfiltered mean gray-level attenuation, coarse entropy, and kurtosis) showed an improved AUC of 0.92. CONCLUSION. High entropy revealed with CTTA may be used to differentiate low-attenuation RCC from cysts at unenhanced CT; this technique performs as well as expert readers.

Unresectable pancreatic ductal adenocarcinoma: Role of CT quantitative imaging biomarkers for predicting outcomes of patients treated with chemotherapy.

OBJECTIVES: The primary aim of this study was to determine if computed tomographic (CT) texture analysis measurements of the tumor are independently associated with progression-free survival (PFS) and overall survival (OS) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC), including both unresectable locally advanced and metastatic PDAC, who were treated with chemotherapy. METHODS: After an institutional review board waiver was obtained, contrast material-enhanced CT studies in 41 patients with unresectable PDAC who underwent contrast-enhanced CT before chemotherapy between 2014 and 2017 were analyzed in terms of tumor texture, with quantification of mean gray-level intensity (Mean), entropy, mean of positive pixels (MPP), kurtosis, standard deviation (SD), and skewness for fine to coarse textures (spatial scaling factor (SSF) 0-6, respectively). The association between pretreatment and posttreatment texture parameters, as well as Δ value (difference between posttreatment and pretreatment texture parameters), and survival time was assessed by using Cox proportional hazards models and Kaplan-Meier analysis. RESULTS: Findings from the multivariate Cox model indicated that tumor size, tumor SD (HR, 0.942; 95% CI: 0.898, 0.988) and skewness (HR, 0.407; 95% CI: 0.172, 0.962) measurements with SSF = 3, and tumor SD (HR, 0.958; 95% CI: 0.92, 0.997) measurements with SSF = 4 were significantly and independently associated with PFS, while tumor size and tumor SD (HR, 0.928; 95% CI: 0.882, 0.976) measurements with SSF = 3 were significantly and independently associated with OS. None of the post-therapy texture parameters or Δ value had a significant association with OS or PFS in multivariate Cox regression models. Medium SD (SSF = 3) of more than 38.38 and coarse SD (SSF = 4) of more than 40.67 were associated with longer PFS after chemotherapy (for SSF = 3, median PFS was 10.0 vs 6.0 months [P = 0.024], and for SSF = 4, median PFS was 12.0 vs 6.0 months [P = 0.003]). SD of 38.38 or greater (SSF = 3) as a dichotomized variable was a significant positive prognostic factor for OS (median OS, 20.0 vs 9.0 months [P = 0.04]). Survival models that included a combination of pretreatment SD (SSF = 3) with tumor size, had the potential to perform better than SD alone, while having no statistical significance in this study (area under the ROC curve, 0.756 vs 0.715 [P = 0.066]). CONCLUSIONS: Pretreatment CT quantitative imaging biomarkers from texture analysis are associated with PFS and OS in patients with unresectable PDAC who were treated with chemotherapy, and the combination of pretreatment texture parameters and tumor size have the potential to perform better in survival models than imaging biomarker alone.

Texture analysis of small renal cell carcinomas at MDCT for predicting relevant histologic and protein biomarkers.

PURPOSE: To assess CT texture features of small renal cell carcinomas (≤ 4cm) for association with key pathologic features including protein biomarkers. METHODS: Quantitative CT texture analysis (CTTA) of small renal cancers (≤ 4cm) was performed on non-contrast and portal venous phase abdominal MDCT scans with an ROI drawn at the largest cross-sectional diameter of the tumor using commercially available software. Texture parameters including mean pixel attenuation, the standard deviation (SD) of the pixel distribution histogram, entropy, the mean of positive pixels, the skewness (i.e., asymmetry) of the pixel histogram, kurtosis (i.e., peakness) of the pixel histogram, and the percentage of positive pixels were correlated with pathologic data from surgical resection, including histology and nuclear grade, as well as microarray analysis in a subset (n = 40) including Ki67 index, CRP, and neovascularization (CD105/CD31). RESULTS: Portal venous phase images were available in 249 patients (105 women, 144 men; mean age, 56.7 years) with tumors ≤ 4cm (mean, median, range, ± SD; 2.66, 2.60, 0.3-4.0 ± 0.85 cm). CT texture features of standard deviation, mean of the positive pixels, and entropy of the pixel histogram were significantly associated with histologic cell type (clear vs. non-clear; p < 0.001). Entropy and mean of the positive pixels also showed an association with nuclear grade, although not statistically significant. In the microarray analysis subset, kurtosis of the pixel histogram was associated with CD105/CD31 (p = 0.05). SD also showed some association with CD 105 positivity (p = 0.02) and CAIX expression (p = 0.01). Non-contrast CT images were available in 174 patients (72 women, 102 men; mean age, 57.5 years). Although the association with histology was not as strong as on the portal venous phase, in the subset of patients with microarray data, SD was found to correlate with CRP (p = 0.08), kurtosis with CRP (p = 0.004), CD105/CD31 (p = 0.002), and with Ki 67 index (p < 0.001). CONCLUSION: CT texture features were significantly associated with important histopathologic features in small renal cancers. These non-invasive measures can be performed retrospectively and may provide useful information when determining follow-up and treatment of small renal cancers.

Multidetector Computed Tomography for Retrospective, Noninvasive Staging of Liver Fibrosis.

Although not traditionally used to assess hepatic fibrosis, computed tomography (CT) is fast, accessible, robust, and commonly used for abdominal indications. CT metrics are often easily retrospectively obtained without special equipment. Metrics such as liver segmental volume ratio, which quantifies regional hepatic volume changes; splenic volume; and liver surface nodularity scoring show diagnostic performance comparable to elastography techniques for detecting significant and advanced fibrosis. Other emerging CT tools, such as CT texture analysis and fractional extracellular volume, have also shown promise in identifying fibrosis and warrant further study.

Discriminatory CT-textural features in splenic infiltration of lymphoma versus splenomegaly in liver cirrhosis versus normal spleens in controls and evaluation of their role for longitudinal lymphoma monitoring.

PURPOSE: To find CT-texture analysis (CTTA) features for the discrimination of splenomegaly due to diffuse lymphoma involvement and liver cirrhosis versus normal-sized spleens in controls and to assess their potential role for longitudinal lymphoma monitoring. MATERIAL AND METHODS: We had retrospectively identified 74 subjects with diffuse splenic involvement due to lymphoma (n = 29) and liver cirrhosis (n = 30), and healthy controls (n = 15), who underwent contrast-enhanced abdominal CT between August 2013 and October 2017. CTTA evaluation included heterogeneity, intensity, average, deviation, skewness, entropy of co-occurrence, number non-uniformity (NGLDM) and entropy NGLDM. A greater than 50% reduction of spleen volume after chemotherapy was considered proof for splenic involvement. RESULTS: There were significant differences of splenic CTTA-values before and after treatment of patients with lymphoma, including mean of entropy(p < .001), uniformity of average(p < .001), uniformity of deviation(p = .002) and entropy of skewness(p < .001). Significant differences of splenic CTTA-values in subjects with lymphoma vs. healthy controls were found for mean intensity(p < .001), mean average(p < .001), and entropy of deviation(p < .001). No significant differences in splenic CTTA-values were found in subjects with lymphoma that reached complete remission vs. controls. Splenic CTTA values mean intensity(p = .002) and mean average(p = .004) were significantly different between subjects with untreated lymphoma and subjects with liver cirrhosis. At end-of-treatment all lymphomas reached complete remission. Entropy/uniformity of heterogeneity(p < .001), mean intensity(p = .007), mean average (p = .007), uniformity of average(p = .008) and mean/entropy/uniformity of skewness(p = .001) measured at this time differed significantly from baseline. CONCLUSIONS: CTTA features in subjects with splenomegaly due to lymphoma and liver cirrhosis differ significantly from those of healthy controls and can be also used for monitoring lymphoma treatment. Quantitative CTTA features may increase the accuracy of diagnosing causes of splenomegaly.