Radiomics Correlation to CD68+ Tumor-Associated Macrophages in Clear Cell Renal Cell Carcinoma.

INTRODUCTION: Renal cell carcinoma (RCC) is the ninth most common cancer worldwide, with clear cell RCC (ccRCC) being the most frequent histological subtype. The tumor immune microenvironment (TIME) of ccRCC is an important factor to guide treatment, but current assessments are tissue-based, which can be time-consuming and resource-intensive. In this study, we used radiomics extracted from clinically performed computed tomography (CT) as a noninvasive surrogate for CD68 tumor-associated macrophages (TAMs), a significant component of ccRCC TIME. METHODS: TAM population was measured by CD68+/PanCK+ ratio and tumor-TAM clustering was measured by normalized K function calculated from multiplex immunofluorescence (mIF). A total of 1,076 regions on mIF slides from 78 patients were included. Radiomic features were extracted from multiphase CT of the ccRCC tumor. Statistical machine learning models, including random forest, Adaptive Boosting, and ElasticNet, were used to predict TAM population and tumor-TAM clustering. RESULTS: The best models achieved an area under the ROC curve of 0.81 (95% CI: [0.69, 0.92]) for TAM population and 0.77 (95% CI: [0.66, 0.88]) for tumor-TAM clustering, respectively. CONCLUSION: Our study demonstrates the potential of using CT radiomics-derived imaging markers as a surrogate for assessment of TAM in ccRCC for real-time treatment response monitoring and patient selection for targeted therapies and immunotherapies.

Radiogenomic Associations Clear Cell Renal Cell Carcinoma: An Exploratory Study.

INTRODUCTION: This study investigates how quantitative texture analysis can be used to non-invasively identify novel radiogenomic correlations with clear cell renal cell carcinoma (ccRCC) biomarkers. METHODS: The Cancer Genome Atlas-Kidney Renal Clear Cell Carcinoma open-source database was used to identify 190 sets of patient genomic data that had corresponding multiphase contrast-enhanced CT images in The Cancer Imaging Archive. 2,824 radiomic features spanning fifteen texture families were extracted from CT images using a custom-built MATLAB software package. Robust radiomic features with strong inter-scanner reproducibility were selected. Random forest, AdaBoost, and elastic net machine learning (ML) algorithms evaluated the ability of the selected radiomic features to predict the presence of 12 clinically relevant molecular biomarkers identified from the literature. ML analysis was repeated with cases stratified by stage (I/II vs. III/IV) and grade (1/2 vs. 3/4). 10-fold cross validation was used to evaluate model performance. RESULTS: Before stratification by tumor grade and stage, radiomics predicted the presence of several biomarkers with weak discrimination (AUC 0.60-0.68). Once stratified, radiomics predicted KDM5C, SETD2, PBRM1, and mTOR mutation status with acceptable to excellent predictive discrimination (AUC ranges from 0.70 to 0.86). CONCLUSIONS: Radiomic texture analysis can potentially identify a variety of clinically relevant biomarkers in patients with ccRCC and may have a prognostic implication.

CT-based radiomics stratification of tumor grade and TNM stage of clear cell renal cell carcinoma.

OBJECTIVES: To evaluate the utility of CT-based radiomics signatures in discriminating low-grade (grades 1-2) clear cell renal cell carcinomas (ccRCC) from high-grade (grades 3-4) and low TNM stage (stages I-II) ccRCC from high TNM stage (stages III-IV). METHODS: A total of 587 subjects (mean age 60.2 years ± 12.2; range 22-88.7 years) with ccRCC were included. A total of 255 tumors were high grade and 153 were high stage. For each subject, one dominant tumor was delineated as the region of interest (ROI). Our institutional radiomics pipeline was then used to extract 2824 radiomics features across 12 texture families from the manually segmented volumes of interest. Separate iterations of the machine learning models using all extracted features (full model) as well as only a subset of previously identified robust metrics (robust model) were developed. Variable of importance (VOI) analysis was performed using the out-of-bag Gini index to identify the top 10 radiomics metrics driving each classifier. Model performance was reported using area under the receiver operating curve (AUC). RESULTS: The highest AUC to distinguish between low- and high-grade ccRCC was 0.70 (95% CI 0.62-0.78) and the highest AUC to distinguish between low- and high-stage ccRCC was 0.80 (95% CI 0.74-0.86). Comparable AUCs of 0.73 (95% CI 0.65-0.8) and 0.77 (95% CI 0.7-0.84) were reported using the robust model for grade and stage classification, respectively. VOI analysis revealed the importance of neighborhood operation-based methods, including GLCM, GLDM, and GLRLM, in driving the performance of the robust models for both grade and stage classification. CONCLUSION: Post-validation, CT-based radiomics signatures may prove to be useful tools to assess ccRCC grade and stage and could potentially add to current prognostic models. Multiphase CT-based radiomics signatures have potential to serve as a non-invasive stratification schema for distinguishing between low- and high-grade as well as low- and high-stage ccRCC. KEY POINTS: • Radiomics signatures derived from clinical multiphase CT images were able to stratify low- from high-grade ccRCC, with an AUC of 0.70 (95% CI 0.62-0.78). • Radiomics signatures derived from multiphase CT images yielded discriminative power to stratify low from high TNM stage in ccRCC, with an AUC of 0.80 (95% CI 0.74-0.86). • Models created using only robust radiomics features achieved comparable AUCs of 0.73 (95% CI 0.65-0.80) and 0.77 (95% CI 0.70-0.84) to the model with all radiomics features in classifying ccRCC grade and stage, respectively.

Whole-tumor 3D volumetric MRI-based radiomics approach for distinguishing between benign and malignant soft tissue tumors.

OBJECTIVES: Our purpose was to differentiate between malignant from benign soft tissue neoplasms using a combination of MRI-based radiomics metrics and machine learning. METHODS: Our retrospective study identified 128 histologically diagnosed benign (n = 36) and malignant (n = 92) soft tissue lesions. 3D ROIs were manually drawn on 1 sequence of interest and co-registered to other sequences obtained during the same study. One thousand seven hundred eight radiomics features were extracted from each ROI. Univariate analyses with supportive ROC analyses were conducted to evaluate the discriminative power of predictive models constructed using Real Adaptive Boosting (Adaboost) and Random Forest (RF) machine learning approaches. RESULTS: Univariate analyses demonstrated that 36.89% of individual radiomics varied significantly between benign and malignant lesions at the p ≤ 0.05 level. Adaboost and RF performed similarly well, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81), respectively, after 10-fold cross-validation. Restricting the machine learning models to only sequences extracted from T2FS and STIR sequences maintained comparable performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84), respectively. CONCLUSION: Machine learning decision classifiers constructed from MRI-based radiomics features show promising ability to preoperatively discriminate between benign and malignant soft tissue masses. Our approach maintains applicability even when the dataset is restricted to T2FS and STIR fluid-sensitive sequences, which may bolster practicality in clinical application scenarios by eliminating the need for complex co-registrations for multisequence analysis. KEY POINTS: • Predictive models constructed from MRI-based radiomics data and machine learning-augmented approaches yielded good discriminative power to correctly classify benign and malignant lesions on preoperative scans, with AUCs of 0.77 (95% CI 0.68-0.85) and 0.72 (95% CI 0.63-0.81) for Real Adaptive Boosting (Adaboost) and Random Forest (RF), respectively. • Restricting the models to only use metrics extracted from T2 fat-saturated (T2FS) and Short-Tau Inversion Recovery (STIR) sequences yielded similar performance, with AUCs of 0.73 (95% CI 0.64-0.82) and 0.75 (95% CI 0.65-0.84) for Adaboost and RF, respectively. • Radiomics-based machine learning decision classifiers constructed from multicentric data more closely mimic the real-world practice environment and warrant additional validation ahead of prospective implementation into clinical workflows.

Shape and texture-based radiomics signature on CT effectively discriminates benign from malignant renal masses.

OBJECTIVES: Using a radiomics framework to quantitatively analyze tumor shape and texture features in three dimensions, we tested its ability to objectively and robustly distinguish between benign and malignant renal masses. We assessed the relative contributions of shape and texture metrics separately and together in the prediction model. MATERIALS AND METHODS: Computed tomography (CT) images of 735 patients with 539 malignant and 196 benign masses were segmented in this retrospective study. Thirty-three shape and 760 texture metrics were calculated per tumor. Tumor classification models using shape, texture, and both metrics were built using random forest and AdaBoost with tenfold cross-validation. Sensitivity analyses on five sub-cohorts with respect to the acquisition phase were conducted. Additional sensitivity analyses after multiple imputation were also conducted. Model performance was assessed using AUC. RESULTS: Random forest classifier showed shape metrics featuring within the top 10% performing metrics regardless of phase, attaining the highest variable importance in the corticomedullary phase. Convex hull perimeter ratio is a consistently high-performing shape feature. Shape metrics alone achieved an AUC ranging 0.64-0.68 across multiple classifiers, compared with 0.67-0.75 and 0.68-0.75 achieved by texture-only and combined models, respectively. CONCLUSION: Shape metrics alone attain high prediction performance and high variable importance in the combined model, while being independent of the acquisition phase (unlike texture). Shape analysis therefore should not be overlooked in its potential to distinguish benign from malignant tumors, and future radiomics platforms powered by machine learning should harness both shape and texture metrics. KEY POINTS: • Current radiomics research is heavily weighted towards texture analysis, but quantitative shape metrics should not be ignored in their potential to distinguish benign from malignant renal tumors. • Shape metrics alone can attain high prediction performance and demonstrate high variable importance in the combined shape and texture radiomics model. • Any future radiomics platform powered by machine learning should harness both shape and texture metrics, especially since tumor shape (unlike texture) is independent of the acquisition phase and more robust from the imaging variations.

Identification of robust and reproducible CT-texture metrics using a customized 3D-printed texture phantom.

OBJECTIVE: The objective of this study was to evaluate the robustness and reproducibility of computed tomography-based texture analysis (CTTA) metrics extracted from CT images of a customized texture phantom built for assessing the association of texture metrics to three-dimensional (3D) printed progressively increasing textural heterogeneity. MATERIALS AND METHODS: A custom-built 3D-printed texture phantom comprising of six texture patterns was used to evaluate the robustness and reproducibility of a radiomics panel under a variety of routine abdominal imaging protocols. The phantom was scanned on four CT scanners (Philips, Canon, GE, and Siemens) to assess reproducibility. The robustness assessment was conducted by imaging the texture phantom across different CT imaging parameters such as slice thickness, field of view (FOV), tube voltage, and tube current for each scanner. The texture panel comprised of 387 features belonging to 15 subgroups of texture extraction methods (e.g., Gray-level Co-occurrence Matrix: GLCM). Twelve unique image settings were tested on all the four scanners (e.g., FOV125). Interclass correlation two-way mixed with absolute agreement (ICC3) was used to assess the robustness and reproducibility of radiomic features. Linear regression was used to test the association between change in radiomic features and increased texture heterogeneity. Results were summarized in heat maps. RESULTS: A total of 5612 (23.2%) of 24 090 features showed excellent robustness and reproducibility (ICC ≥ 0.9). Intensity, GLCM 3D, and gray-level run length matrix (GLRLM) 3D features showed best performance. Among imaging variables, changes in slice thickness affected all metrics more intensely compared to other imaging variables in reducing the ICC3. From the analysis of linear trend effect of the CTTA metrics, the top three metrics with high linear correlations across all scanners and scanning settings were from the GLRLM 2D/3D and discrete cosine transform (DCT) texture family. CONCLUSION: The choice of scanner and imaging protocols affect texture metrics. Furthermore, not all CTTA metrics have a linear association with linearly varying texture patterns.

Myocardial Radiomics in Cardiac MRI.

OBJECTIVE. The purpose of this article is to review the nascent field of radiomics in cardiac MRI. CONCLUSION. Cardiac MRI produces a large number of images in a fairly inefficient manner with sometimes limited clinical application. In the era of precision medicine, there is increasing need for imaging to account for a broader array of diseases in an efficient and objective manner. Radiomics, the extraction and analysis of quantitative imaging features from medical imaging, may offer potential solutions to this need.

Radiomics in Pulmonary Lesion Imaging.

OBJECTIVE: Diagnostic imaging has traditionally relied on a limited set of qualitative imaging characteristics for the diagnosis and management of lung cancer. Radiomics-the extraction and analysis of quantitative features from imaging-can identify additional imaging characteristics that cannot be seen by the eye. These features can potentially be used to diagnose cancer, identify mutations, and predict prognosis in an accurate and noninvasive fashion. This article provides insights about trends in radiomics of lung cancer and challenges to widespread adoption. CONCLUSION: Radiomic studies are currently limited to a small number of cancer types. Its application across various centers are nonstandardized, leading to difficulties in comparing and generalizing results. The tools available to apply radiomics are specialized and limited in scope, blunting widespread use and clinical integration in the general population. Increasing the number of multicenter studies and consortiums and inclusion of radiomics in resident training will bring more attention and clarity to the growing field of radiomics.

Texture Analysis of Imaging: What Radiologists Need to Know.

OBJECTIVE: Radiologic texture is the variation in image intensities within an image and is an important part of radiomics. The objective of this article is to discuss some parameters that affect the performance of texture metrics and propose recommendations that can guide both the design and evaluation of future radiomics studies. CONCLUSION: A variety of texture-extraction techniques are used to assess clinical imaging data. Currently, no consensus exists regarding workflow, including acquisition, extraction, or reporting of variable settings leading to poor reproducibility.

Reliability of CT-based texture features: Phantom study.

OBJECTIVE: To determine the intra-, inter- and test-retest variability of CT-based texture analysis (CTTA) metrics. MATERIALS AND METHODS: In this study, we conducted a series of CT imaging experiments using a texture phantom to evaluate the performance of a CTTA panel on routine abdominal imaging protocols. The phantom comprises of three different regions with various textures found in tumors. The phantom was scanned on two CT scanners viz. the Philips Brilliance 64 CT and Toshiba Aquilion Prime 160 CT scanners. The intra-scanner variability of the CTTA metrics was evaluated across imaging parameters such as slice thickness, field of view, post-reconstruction filtering, tube voltage, and tube current. For each scanner and scanning parameter combination, we evaluated the performance of eight different types of texture quantification techniques on a predetermined region of interest (ROI) within the phantom image using 235 different texture metrics. We conducted the repeatability (test-retest) and robustness (intra-scanner) test on both the scanners and the reproducibility test was conducted by comparing the inter-scanner differences in the repeatability and robustness to identify reliable CTTA metrics. Reliable metrics are those metrics that are repeatable, reproducible and robust. RESULTS: As expected, the robustness, repeatability and reproducibility of CTTA metrics are variably sensitive to various scanner and scanning parameters. Entropy of Fast Fourier Transform-based texture metrics was overall most reliable across the two scanners and scanning conditions. Post-processing techniques that reduce image noise while preserving the underlying edges associated with true anatomy or pathology bring about significant differences in radiomic reliability compared to when they were not used. CONCLUSION: Following large-scale validation, identification of reliable CTTA metrics can aid in conducting large-scale multicenter CTTA analysis using sample sets acquired using different imaging protocols, scanners etc.

Differentiation of Predominantly Solid Enhancing Lipid-Poor Renal Cell Masses by Use of Contrast-Enhanced CT: Evaluating the Role of Texture in Tumor Subtyping.

OBJECTIVE: The purpose of this study was to assess the accuracy of a panel of texture features extracted from clinical CT in differentiating benign from malignant solid enhancing lipid-poor renal masses. MATERIALS AND METHODS: In a retrospective case-control study of 174 patients with predominantly solid nonmacroscopic fat-containing enhancing renal masses, 129 cases of malignant renal cell carcinoma were found, including clear cell, papillary, and chromophobe subtypes. Benign renal masses-oncocytoma and lipid-poor angiomyolipoma-were found in 45 patients. Whole-lesion ROIs were manually segmented and coregistered from the standard-of-care multiphase contrast-enhanced CT (CECT) scans of these patients. Pathologic diagnosis of all tumors was obtained after surgical resection. CECT images of the renal masses were used as inputs to a CECT texture analysis panel comprising 31 texture metrics derived with six texture methods. Stepwise logistic regression analysis was used to select the best predictor among all candidate predictors from each of the texture methods, and their performance was quantified by AUC. RESULTS: Among the texture predictors aiding renal mass subtyping were entropy, entropy of fast-Fourier transform magnitude, mean, uniformity, information measure of correlation 2, and sum of averages. These metrics had AUC values ranging from good (0.80) to excellent (0.98) across the various subtype comparisons. The overall CECT-based tumor texture model had an AUC of 0.87 (p < 0.05) for differentiating benign from malignant renal masses. CONCLUSION: The CT texture statistical model studied was accurate for differentiating benign from malignant solid enhancing lipid-poor renal masses.

A Decision-Support Tool for Renal Mass Classification.

We investigate the viability of statistical relational machine learning algorithms for the task of identifying malignancy of renal masses using radiomics-based imaging features. Features characterizing the texture, signal intensity, and other relevant metrics of the renal mass were extracted from multiphase contrast-enhanced computed tomography images. The recently developed formalism of relational functional gradient boosting (RFGB) was used to learn human-interpretable models for classification. Experimental results demonstrate that RFGB outperforms many standard machine learning approaches as well as the current diagnostic gold standard of visual qualification by radiologists.

Empowering breast cancer diagnosis and radiology practice: advances in artificial intelligence for contrast-enhanced mammography.

Artificial intelligence (AI) applications in breast imaging span a wide range of tasks including decision support, risk assessment, patient management, quality assessment, treatment response assessment and image enhancement. However, their integration into the clinical workflow has been slow due to the lack of a consensus on data quality, benchmarked robust implementation, and consensus-based guidelines to ensure standardization and generalization. Contrast-enhanced mammography (CEM) has improved sensitivity and specificity compared to current standards of breast cancer diagnostic imaging i.e., mammography (MG) and/or conventional ultrasound (US), with comparable accuracy to MRI (current diagnostic imaging benchmark), but at a much lower cost and higher throughput. This makes CEM an excellent tool for widespread breast lesion characterization for all women, including underserved and minority women. Underlining the critical need for early detection and accurate diagnosis of breast cancer, this review examines the limitations of conventional approaches and reveals how AI can help overcome them. The Methodical approaches, such as image processing, feature extraction, quantitative analysis, lesion classification, lesion segmentation, integration with clinical data, early detection, and screening support have been carefully analysed in recent studies addressing breast cancer detection and diagnosis. Recent guidelines described by Checklist for Artificial Intelligence in Medical Imaging (CLAIM) to establish a robust framework for rigorous evaluation and surveying has inspired the current review criteria.

Spatial assessments in texture analysis: what the radiologist needs to know.

To date, studies investigating radiomics-based predictive models have tended to err on the side of data-driven or exploratory analysis of many thousands of extracted features. In particular, spatial assessments of texture have proven to be especially adept at assessing for features of intratumoral heterogeneity in oncologic imaging, which likewise may correspond with tumor biology and behavior. These spatial assessments can be generally classified as spatial filters, which detect areas of rapid change within the grayscale in order to enhance edges and/or textures within an image, or neighborhood-based methods, which quantify gray-level differences of neighboring pixels/voxels within a set distance. Given the high dimensionality of radiomics datasets, data dimensionality reduction methods have been proposed in an attempt to optimize model performance in machine learning studies; however, it should be noted that these approaches should only be applied to training data in order to avoid information leakage and model overfitting. While area under the curve of the receiver operating characteristic is perhaps the most commonly reported assessment of model performance, it is prone to overestimation when output classifications are unbalanced. In such cases, confusion matrices may be additionally reported, whereby diagnostic cut points for model predicted probability may hold more clinical significance to clinical colleagues with respect to related forms of diagnostic testing.

Predicting Soft Tissue Sarcoma Response to Neoadjuvant Chemotherapy Using an MRI-Based Delta-Radiomics Approach.

OBJECTIVES: To evaluate the performance of machine learning-augmented MRI-based radiomics models for predicting response to neoadjuvant chemotherapy (NAC) in soft tissue sarcomas. METHODS: Forty-four subjects were identified retrospectively from patients who received NAC at our institution for pathologically proven soft tissue sarcomas. Only subjects who had both a baseline MRI prior to initiating chemotherapy and a post-treatment scan at least 2 months after initiating chemotherapy and prior to surgical resection were included. 3D ROIs were used to delineate whole-tumor volumes on pre- and post-treatment scans, from which 1708 radiomics features were extracted. Delta-radiomics features were calculated by subtraction of baseline from post-treatment values and used to distinguish treatment response through univariate analyses as well as machine learning-augmented radiomics analyses. RESULTS: Though only 4.74% of variables overall reached significance at p ≤ 0.05 in univariate analyses, Laws Texture Energy (LTE)-derived metrics represented 46.04% of all such features reaching statistical significance. ROC analyses similarly failed to predict NAC response, with AUCs of 0.40 (95% CI 0.22-0.58) and 0.44 (95% CI 0.26-0.62) for RF and AdaBoost, respectively. CONCLUSION: Overall, while our result was not able to separate NAC responders from non-responders, our analyses did identify a subset of LTE-derived metrics that show promise for further investigations. Future studies will likely benefit from larger sample size constructions so as to avoid the need for data filtering and feature selection techniques, which have the potential to significantly bias the machine learning procedures.

Characterizing breast masses using an integrative framework of machine learning and CEUS-based radiomics.

AIMS: We evaluated the performance of contrast-enhanced ultrasound (CEUS) based on radiomics analysis to distinguish benign from malignant breast masses. METHODS: 131 women with suspicious breast masses (BI-RADS 4a, 4b, or 4c) who underwent CEUS examinations (using intravenous injection of perflutren lipid microsphere or sulfur hexafluoride lipid-type A microspheres) prior to ultrasound-guided biopsies were retrospectively identified. Post biopsy pathology showed 115 benign and 16 malignant masses. From the cine clip of the CEUS exams obtained using the built-in GE scanner software, breast masses and adjacent normal tissue were then manually segmented using the ImageJ software. One frame representing each of the four phases: precontrast, early, peak, and delay enhancement were selected post segmentation from each CEUS clip. 112 radiomic metrics were extracted from each segmented tissue normalized breast mass using custom Matlab® code. Linear and nonlinear machine learning (ML) methods were used to build the prediction model to distinguish benign from malignant masses. tenfold cross-validation evaluated model performance. Area under the curve (AUC) was used to quantify prediction accuracy. RESULTS: Univariate analysis found 35 (38.5%) radiomic variables with p < 0.05 in differentiating between benign from malignant masses. No feature selection was performed. Predictive models based on AdaBoost reported an AUC = 0.72 95% CI (0.56, 0.89), followed by Random Forest with an AUC = 0.71 95% CI (0.56, 0.87). CONCLUSIONS: CEUS based texture metrics can distinguish between benign and malignant breast masses, which can, in turn, lead to reduced unnecessary breast biopsies.

Juxtatumoral perinephric fat analysis in clear cell renal cell carcinoma.

PURPOSE: The purpose of the study was to evaluate the feasibility of using contrast-enhanced computed tomography (CECT)-based texture analysis (CTTA) metrics to differentiate between juxtatumoral perinephric fat (JPF) surrounding low-grade (ISUP 1-2) versus high-grade (ISUP 3-4) clear cell renal cell carcinoma (ccRCC). METHODS: In this IRB-approved study, we retrospectively queried the surgical database between June 2009 and April 2016 and identified 83 patients with pathologically confirmed ccRCC (low grade: n = 54, mean age = 61.5 years, 18F/35M; high grade n = 30, mean age = 61.7 years, 8F/22M) who also had pre-operative multiphase CT acquisitions. CT images were transferred to a 3D workstation, and nephrographic phase JPF regions were manually segmented. Using an in-house developed Matlab program, a CTTA panel comprising of texture metrics extracted using six different methods, histogram, 2D- and 3D-Gray-level co-occurrence matrix (GLCM) and Gray-level difference matrix (GLDM), and 2D-Fast Fourier Transform (FFT) analyses, was applied to the segmented images to assess JPF textural heterogeneity in low- versus high-grade ccRCC. Univariate analysis and receiver-operator characteristics (ROC) analysis were used to assess interclass differences in texture metrics and their prediction accuracy, respectively. RESULTS: All methods except GLCM consistently revealed increased heterogeneity in the JPF surrounding high- versus low-grade ccRCC. FFT showed increased complexity index (p < 0.01). Histogram analysis showed increased kurtosis and positive skewness in (p < 0.03), and GLDM analysis showed decreased measure of correlation coefficient (MCC) (p < 0.04). Several of the GLCM metrics showed statistically significant (p < 0.04) textural differences between the two groups, but with no consistent trend. ROC analysis showed that MCC in GLCM analysis had an area under the curve of 0.75. CONCLUSIONS: Our study suggests that CTTA of ccRCC shows statistically significant textural differences in JPF surrounding high- versus low-grade ccRCC.

Differentiating solid, non-macroscopic fat containing, enhancing renal masses using fast Fourier transform analysis of multiphase CT.

OBJECTIVE: To test the feasibility of two-dimensional fast Fourier transforms (FFT)-based imaging metrics in differentiating solid, non-macroscopic fat containing, enhancing renal masses using contrast-enhanced CT images. We quantify image-based intratumoral textural variations (indicator of tumor heterogeneity) using frequency-based (FFT) imaging metrics. METHODS: In this Institutional Review Board approved, Health Insurance Portability and Accountability Act -compliant, retrospective case-control study, we evaluated 156 patients with predominantly solid, non-macroscopic fat containing, enhancing renal masses identified between June 2009 and June 2016. 110 cases (70%) were malignant RCC, including clear cell, papillary and chromophobe subtypes and, 46 cases (30%) were benign renal masses: oncocytoma and lipid-poor angiomyolipoma. Whole lesions were manually segmented using Synapse 3D (Fujifilm, CT) and co-registered from the multiphase CT acquisitions for each tumor. Pathological diagnosis of all tumors was obtained following surgical resection. Matlab function, FFT2 was used to perform the image to frequency transformation. RESULTS: A Wilcoxon rank sum test showed that FFT-based metrics were significantly (p < 0.005) different between 1. benign vs malignant renal masses, 2. oncocytoma vs clear cell renal cell carcinoma and 3. oncocytoma vs lipid-poor angiomyolipoma. Receiver operator characteristics analysis revealed reasonable discrimination (area under the curve >0.7, p < 0.05) within these three groups of comparisons. CONCLUSION: In combination with other metrics, FFT-metrics may improve patient management and potentially help differentiate other renal tumors. Advances in knowledge: We report for the first time that FFT-based metrics can differentiate between some solid, non-macroscopic fat containing, enhancing renal masses using their contrast-enhanced CT data.

Quantitative Contour Analysis as an Image-based Discriminator Between Benign and Malignant Renal Tumors.

OBJECTIVE: To investigate whether morphologic analysis can differentiate between benign and malignant renal tumors on clinically acquired imaging. MATERIALS AND METHODS: Between 2009 and 2014, 3-dimensional tumor volumes were manually segmented from contrast-enhanced computerized tomography (CT) images from 150 patients with predominantly solid, nonmacroscopic fat-containing renal tumors: 100 renal cell carcinomas and 50 benign lesions (eg, oncocytoma and lipid-poor angiomyolipoma). Tessellated 3-dimensional tumor models were created from segmented voxels using MATLAB code. Eleven shape descriptors were calculated: sphericity, compactness, mean radial distance, standard deviation of the radial distance, radial distance area ratio, zero crossing, entropy, Feret ratio, convex hull area and convex hull perimeter ratios, and elliptic compactness. Morphometric parameters were compared using the Wilcoxon rank-sum test to investigate whether malignant renal masses demonstrate more morphologic irregularity than benign ones. RESULTS: Only CHP in sagittal orientation (median 0.96 vs 0.97) and EC in coronal orientation (median 0.92 vs 0.93) differed significantly between malignant and benign masses (P = .04). When comparing these 2 metrics between coronal and sagittal orientations, similar but nonsignificant trends emerged (P = .07). Other metrics tested were not significantly different in any imaging plane. CONCLUSION: Computerized image analysis is feasible using shape descriptors that otherwise cannot be visually assessed and used without quantification. Shape analysis via the transverse orientation may be reasonable, but encompassing all 3 planar dimensions to characterize tumor contour can achieve a more comprehensive evaluation. Two shape metrics (CHP and EC) may help distinguish benign from malignant renal tumors, an often challenging goal to achieve on imaging and biopsy.

Liver-Directed Human Amniotic Epithelial Cell Transplantation Improves Systemic Disease Phenotype in Hurler Syndrome Mouse Model.

Mucopolysaccharidosis type 1 (MPS1) is an inherited lysosomal storage disorder caused by a deficiency in the glycosaminoglycan (GAG)-degrading enzyme α-l-iduronidase (IDUA). In affected patients, the systemic accumulation of GAGs results in skeletal dysplasia, neurological degeneration, multiple organ dysfunction, and early death. Current therapies, including enzyme replacement and bone marrow transplant, improve life expectancy but the benefits to skeletal and neurological phenotypes are limited. In this study, we tested the therapeutic efficacy of liver-directed transplantation of a placental stem cell, which possesses multilineage differentiation potential, low immunogenicity, and high lysosomal enzyme activity. Unfractionated human amniotic epithelial cells (hAECs) were transplanted directly into the liver of immunodeficient Idua knockout mouse neonates. The hAECs engraftment was immunohistochemically confirmed with anti-human mitochondria staining. Enzyme activity assays indicated that hAECs transplantation restored IDUA function in the liver and significantly decreased urinary GAG excretion. Histochemical and micro-computed tomography analyses revealed reduced GAG deposition in the phalanges joints and composition/morphology improvement of cranial and facial bones. Neurological assessment in the hAEC treated mice showed significant improvement of sensorimotor coordination in the hAEC treated mice compared to untreated mice. Results confirm that partial liver cell replacement with placental stem cells can provide long-term (>20 weeks) and systemic restoration of enzyme function, and lead to significant phenotypic improvement in the MPS1 mouse model. This preclinical data indicate that liver-directed placental stem cell transplantation may improve skeletal and neurological phenotypes of MPS1 patients. Stem Cells Translational Medicine 2017;6:1583-1594.