Mean Of Positive Pixels Research Articles

Quantitative CT texture analysis for evaluating histologic grade of urothelial carcinoma.

To investigate the feasibility of using CT texture analysis (CTTA) to differentiate between low- versus high-grade urothelial carcinoma. A total of 105 patients with high-grade urothelial carcinoma (HGUC, n=106) and low-grade urothelial carcinoma (LGUC, n=18) were included in this retrospective study. Both unenhanced and enhanced CT images representing the largest cross-sectional area of the tumor were chosen for CTTA performed using TexRAD software. Comparison of texture parameters, mean gray-level intensity (Mean), standard deviation, entropy, mean of positive pixels (MPP), skewness, and kurtosis were made for the objective. Receiver operating characteristic (ROC) analysis was performed and the area under the ROC curve was calculated for texture parameters that were significantly different (P<0.05) for the purpose. Sensitivity (Se), specificity (Sp), positive predictive value, negative predictive value, and accuracy were calculated using the cut-off value of texture parameter with the highest AUC. Compared to HGUC, LGUC had significantly lower Mean (P=0.001), Entropy (P=0.002), and MPP (P<0.001) on unenhanced and enhanced images and lower SD (P=0.048) on enhanced images. There was no significant difference in skewness or kurtosis at any texture scale on unenhanced and enhanced images. A MPP<24.13 at fine texture scale on unenhanced images identified LGUC from HGUC with the highest AUC of 0.779±0.065 (Se=72.2%, Sp=84.9%, PPV=44.8%, NPV=94.7%, and accuracy=83.1%). CTTA proved to be a feasible tool for differentiating LGUC from HGUC. MPP quantified from fine texture scale on unenhanced images was the optimal diagnostic parameter for estimating histologic grade of urothelial carcinoma.

CT Textural Analysis of Large Primary Renal Cell Carcinomas: Pretreatment Tumor Heterogeneity Correlates With Histologic Findings and Clinical Outcomes.

The purpose of the present study is to determine whether CT texture features of newly diagnosed primary renal cell carcinomas (RCCs) correlate with pathologic features and oncologic outcomes. CT texture analysis was performed on large (> 7 cm; mean size, 9.9 cm) untreated RCCs in 157 patients (52 women and 105 men; mean age, 60.3 years). Measures of tumor heterogeneity, including entropy, kurtosis, skewness, mean, mean of positive pixels, and SD of pixel distribution histogram were derived from multiphasic CT using various filter settings: unfiltered (spatial scaling factor, 0), fine (spatial scaling factor, 2), medium (spatial scaling factor, 3-4), or coarse (spatial scaling factor, 5-6). Texture values were correlated with histologic subtype, nuclear grade, pathologic stage, and clinical outcome. When a coarse filter setting (spatial scaling factor, 6) was used, entropy on portal venous phase CT images was positively associated with clear cell histologic findings (odds ratio [OR], 134; 95% CI, 16-1110; p < 0.001) and was negatively associated with non-clear cell subtype findings (papillary spatial scale factor, 6; OR, 0.016; 95% CI, 0.002-0.132; p < 0.001). ROC curve analysis for entropy (on portal venous phase images obtained with a spatial scaling factor of 6) revealed an AUC of 0.943 (95% CI, 0.892-0.993) for clear cell histologic findings, with similar values noted for non-clear cell histologic findings. The mean of positive pixels and the SD of the pixel distribution histogram were statistically significantly associated with histologic cell type in a similar fashion. Entropy, the SD of the pixel distribution histogram, and the mean of positive pixels were associated with nuclear grade, most prominently when fine or medium texture filters were used (p < 0.05). There was a statistically significant association of texture features noted on unenhanced CT, including the SD of the pixel distribution histogram, the mean of positive pixels, and entropy, with the time to disease recurrence and death due to disease (e.g., for entropy noted on unenhanced CT images obtained with a spatial scaling factor of 6, the hazard ratio was 3.49 [95% CI, 1.55-7.84]; p = 0.002). CT texture features (in particular, entropy, the mean of positive pixels, and the SD of the pixel distribution histogram) are associated with tumor histologic findings, nuclear grade, and outcome measures. The contrast phase does seem to affect heterogeneity measures.

MRI texture analysis (MRTA) of T2-weighted images in Crohn\u2019s disease may provide information on histological and MRI disease activity in patients undergoing ileal resection

ObjectivesTo associate MRI textural analysis (MRTA) with MRI and histological Crohn’s disease (CD) activity.MethodsSixteen patients (mean age 39.5 years, 9 male) undergoing MR enterography before ileal resection were retrospectively analysed. Thirty-six small (≤3 mm) ROIs were placed on T2-weighted images and location-matched histological acute inflammatory scores (AIS) measured. MRI activity (mural thickness, T2 signal, T1 enhancement) (CDA) was scored in large ROIs. MRTA features (mean, standard deviation, mean of positive pixels (MPP), entropy, kurtosis, skewness) were extracted using a filtration histogram technique. Spatial scale filtration (SSF) ranged from 2 to 5 mm. Regression (linear/logistic) tested associations between MRTA and AIS (small ROIs), and CDA/constituent parameters (large ROIs).ResultsSkewness (SSF = 2 mm) was associated with AIS [regression coefficient (rc) 4.27, p = 0.02]. Of 120 large ROI analyses (for each MRI, MRTA feature and SSF), 15 were significant. Entropy (SSF = 2, 3 mm) and kurtosis (SSF = 3 mm) were associated with CDA (rc 0.9, 1.0, −0.45, p = 0.006–0.01). Entropy and mean (SSF = 2–4 mm) were associated with T2 signal [odds ratio (OR) 2.32–3.16, p = 0.02–0.004], [OR 1.22–1.28, p = 0.03–0.04]. MPP (SSF = 2 mm) was associated with mural thickness (OR 0.91, p = 0.04). Kurtosis (SSF = 3 mm), standard deviation (SSF = 5 mm) were associated with decreased T1 enhancement (OR 0.59, 0.42, p = 0.004, 0.007).ConclusionsMRTA features may be associated with CD activity.Key Points• MR texture analysis features may be associated with Crohn’s disease histological activity.• Texture analysis features may correlate with MR-dependent Crohn’s disease activity scores.• The utility of MR texture analysis in Crohn’s disease merits further investigation.

MRI texture analysis parameters of contrast-enhanced T1-weighted images of Crohn's disease differ according to the presence or absence of histological markers of hypoxia and angiogenesis.

PurposeTo investigate if texture analysis parameters of contrast-enhanced MRI differ according to the presence of histological markers of hypoxia and angiogenesis in Crohn’s disease (CD).MethodsSeven CD patients (mean age 38 (19–75), 3 male)) undergoing ileal resection underwent 3T MR enterography including axial ultrafast spoiled gradient-echo T1 post IV gadolinium chelate. Regions of interest were placed in bowel destined for resection and registered to trans-mural histological sections (n = 28 across 7 bowel sections) via MRI of the resected specimen. Microvessel density (MVD) and staining for markers of hypoxia (HIF 1α) and angiogenesis (VEGF) were performed. Texture analysis features were derived utilizing an image filtration-histogram technique at spatial scaling factor (SSF) 0–6 mm, including mean, standard deviation, mean of positive pixels, entropy, kurtosis and skewness and compared according to the presence or absence of histological markers of hypoxia/angiogenesis using Mann–Whitney U/Kruskal–Wallis tests and with the log of MVD using simple linear regression.ResultsMean, standard deviation and mean of positive pixels were significantly lower in sections expressing VEGF. For example at SSF 6 mm, median (inter-quartile range) of mean, standard deviation and mean of positive pixels in those with VEGF expression were 150.1 (134.7), 132.4 (49.2) and 184.0 (91.4) vs. 362.5 (150.2), 216.3 (100.1) and 416.6 (80.0) in those without (p = 0.001, p = 0.004 and p = 0.001), respectively. There was a significant association between skewness and MVD (ratio 1.97 (1.15–3.41)) at SSF = 2 mm.ConclusionsContrast-enhanced MRI texture analysis features significantly differ according to the presence or absence of histological markers of hypoxia and angiogenesis in CD.

Abstract 213: Evaluating high risk BI-RADS 4 mammographic lesions: a pilot trial of textural analysis (TA) as a supplement to digital mammography (DM)

Abstract Background: Although mammographic lesions classified as BI-RADS 4 are considered suspicious for carcinoma - by definition - and biopsy (bx) is therefore always recommended, only 20-30% of such lesions ultimately yield malignancy at biopsy. TA is an ancillary non-subjective quantitative analysis platform that can be performed as an add-on to routine mammographic analysis. The ability of TA to characterize lesions with high rates of heterogeneity led us to hypothesize that TA, as a supplement to routine DM analysis, might aid in selecting patients (pts) for bx vs. serial observation. Methods: A retrospective analysis was performed on 40 screening pts with no history of cancer, with newly identified mammographic densities characterized as BI-RADS 4. Lesions measured 1-3 cm size and had no associated microcalcifications. Twenty pts had confirmed malignant biopsy while the other 20 pts served as age matched controls with similar lesion characteristics but ultimate benign biopsy result. For each lesion, TA was performed on a 1×1cm region of interest (ROI), along with a secondary control ROI of normal breast tissue. Results: Pts with malignant and benign bx had a median age of 53 years (range 28-83) vs. 52 years (range 32-75) (p = NS) and median nodule size 1.5 cm (range 1.0-2.9 cm) vs. 1.3 cm (range 1.0-2.5 cm) (p = NS), respectively. No differences between the groups were seen in menopausal status nor parenchymal density. The mean positive pixel (MPP) value was most predictive of malignancies at a Spatial Scale Frequency (SSF) filter level of 0.8. The median MPP for malignant lesions was 577 vs 730 for benign lesions (p = 0.033). There was no difference between MPP or other TA parameters in normal tissue of either group. Conclusion: TA, as a supplement to DM, may help stratify which women with high-risk BI-RADS 4 densities that better benefit from biopsy vs. those that might be safely followed with serial surveillance. Larger scale studies will be needed to validate these findings and are currently ongoing. Citation Format: Melissa R. Gordon, Erkut Borazanci, Daniel D. Maki, Ron L. Korn. Evaluating high risk BI-RADS 4 mammographic lesions: a pilot trial of textural analysis (TA) as a supplement to digital mammography (DM). [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 213. doi:10.1158/1538-7445.AM2015-213

CT textural analysis of hepatic metastatic colorectal cancer: pre-treatment tumor heterogeneity correlates with pathology and clinical outcomes.

The purpose of the study was to determine if CT texture features of untreated hepatic metastatic colorectal cancer (CRC) relate to pathologic features and clinical outcomes. Tumor texture analysis was performed on single hepatic metastatic lesions on pre-treatment contrast-enhanced CT scans in 77 pts (mean age 58, 34F/43M) using a novel tool. Measures of heterogeneity, including entropy, kurtosis, skewness, mean, mean positive pixels (MPP), and standard deviation (SD) of pixel distribution histogram were derived with filter values corresponding to fine (spatial scaling factor (ssf) 2), medium (ssf 3, 4), and coarse textures (ssf 5, 6). Texture parameters were correlated with tumor grade, baseline serum CEA, and KRAS mutation status. Overall survival was also correlated using Cox proportional hazards models. Single-slice 2D vs. whole-tumor volumetric 3D texture analysis was compared in a subcohort of 20 patients. Entropy, MPP, and SD at medium filtration levels were significantly associated with tumor grade (MPP ssf 3 P=0.002, SD ssf 3 P=0.004, entropy ssf 4 P=0.007). Skewness was negatively associated KRAS mutation (P=0.02). Entropy at coarse filtration levels was associated with survival (Hazard ratio (HR) for death 0.65, 95% CI 0.44-0.95, P=0.03). Texture results for 2D and 3D analysis were similar. CT texture features, particularly entropy, MPP, and SD, are significantly associated with tumor grade in untreated CRC liver metastases. Tumor entropy at coarse filters correlates with overall survival. Single-slice 2D texture analysis appears to be adequate.

Multifunctional Imaging Signature for V-KI-RAS2 Kirsten Rat Sarcoma Viral Oncogene Homolog (KRAS) Mutations in Colorectal Cancer

This study explores the potential for multifunctional imaging to provide a signature for V-KI-RAS2 Kirsten rat sarcoma viral oncogene homolog (KRAS) gene mutations in colorectal cancer. This prospective study approved by the institutional review board comprised 33 patients undergoing PET/CT before surgery for proven primary colorectal cancer. Tumor tissue was examined histologically for presence of the KRAS mutations and for expression of hypoxia-inducible factor-1 (HIF-1) and minichromosome maintenance protein 2 (mcm2). The following imaging parameters were derived for each tumor: (18)F-FDG uptake ((18)F-FDG maximum standardized uptake value [SUVmax]), CT texture (expressed as mean of positive pixels [MPP]), and blood flow measured by dynamic contrast-enhanced CT. A recursive decision tree was developed in which the imaging investigations were applied sequentially to identify tumors with KRAS mutations. Monte Carlo analysis provided mean values and 95% confidence intervals for sensitivity, specificity, and accuracy. The final decision tree comprised 4 decision nodes and 5 terminal nodes, 2 of which identified KRAS mutants. The true-positive rate, false-positive rate, and accuracy (95% confidence intervals) of the decision tree were 82.4% (63.9%-93.9%), 0% (0%-10.4%), and 90.1% (79.2%-96.0%), respectively. KRAS mutants with high (18)F-FDG SUVmax and low MPP showed greater frequency of HIF-1 expression (P = 0.032). KRAS mutants with low (18)F-FDG SUV(max), high MPP, and high blood flow expressed mcm2 (P = 0.036). Multifunctional imaging with PET/CT and recursive decision-tree analysis to combine measurements of tumor (18)F-FDG uptake, CT texture, and perfusion has the potential to identify imaging signatures for colorectal cancers with KRAS mutations exhibiting hypoxic or proliferative phenotypes.

Abstract A2: Exploratory textural CT evaluation of the combination of TRC105 (anti-endoglin monoclonal antibody; MAb) and bevacizumab (BEV) indicates partial response by Choi criteria in BEV refractory advanced cancer patients (pts) and identifies candidate markers of response.

Abstract Background: Endoglin (CD105) is an endothelial cell membrane receptor, highly expressed on angiogenic tumor vessels, that is essential for angiogenesis and upregulated by hypoxia and VEGF inhibition. TRC105 is an anti-endoglin MAb that potentiates VEGF inhibitors in preclinical models. TRC105 10 mg/kg weekly was well tolerated with BEV 10 mg/kg q2wk and the combination demonstrated activity in BEV and VEGF TKI refractory pts. This study assessed radiographic responses to TRC105 + BEV using Choi criteria and tumor morphology by applying novel quantitative textural analysis (QTA: TexRad -University of Sussex, UK) in pts with durable stable disease by RECIST, to determine predictive markers of response. Methods: Contrast enhanced CT scans from 5 pts with advanced solid tumors who demonstrated stable disease by RECIST in a trial of escalating doses of TRC105 (3, 6, 8 or 10 mg/kg/wk) plus BEV were reviewed. Seventeen target lesions were selected from baseline scans and assessed for target lesion diameter, whole lesion density, and tumor volume at baseline and follow-up. QTA analysis was assessed on the same target lesions using six different filter levels at baseline and on follow-up scans. The results were correlated to anatomic tumor response using non-parametric evaluation and regression analysis. Statistical significance was defined as a two-tailed p &amp;lt; 0.05. Results: Scans from 5 patients (median age 56; M:F 2:3; median 4 prior regimens; 3 metastatic colorectal and 2 ovarian cancer) 4 of whom progressed following VEGF inhibitor treatment were selected and demonstrated stable disease by RECIST for at least 4 months (range: 4-14 months) of treatment with TRC105 + BEV. Four of five patients (80%) had partial responses by Choi criteria. Predictive markers of tumor response on baseline scans included 1) elevated mean pixel density (median values of responder (R) vs non responder (NR): 27.2 vs -4.3) that correlated with subsequent tumor size reduction, 2) elevated entropy (a measure of tumor heterogeneity; median R vs NR: 5.1 vs 4.7) that correlated with subsequent decrease in mean tumor volume, and 3) low kurtosis (a measure of tumor heterogeneity; median R vs NR: 0.2 vs 1.1) that correlated with subsequent reduction in lesion density (p&amp;lt;0.01). Mean positive pixel values (an indicator of hypoxia) on follow-up scans correlated with decreased tumor density. Conclusions: Assessment of radiographic response using Choi criteria identified VEGF inhibitor refractory patients who demonstrated partial response to the combination of TRC105 + BEV. Using novel QTA measures, markers of tumor heterogeneity and hypoxia correlated with individual lesion responses and are worthy of prospective evaluation as predictive imaging biomarkers. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A2. Citation Format: Ron L. Korn, Michael S. Gordon, Lee S. Rosen, Francisco Robert, Daniela Matei, Jonathan W. Goldman, David S. Mendelson, E. Gabriela Chiorean, Robert Matthew Strother, Ben K. Seon, Delia Alvarez, Bonne J. Adams, Charles P. Theuer. Exploratory textural CT evaluation of the combination of TRC105 (anti-endoglin monoclonal antibody; MAb) and bevacizumab (BEV) indicates partial response by Choi criteria in BEV refractory advanced cancer patients (pts) and identifies candidate markers of response. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A2.