Survival and life quality of breast cancer patients could be improved by more aggressive chemotherapy for those at high metastasis risk and less intense treatments for low-risk patients. Such personalized treatment cannot be currently achieved due to the insufficient reliability of metastasis risk prognosis. The purpose of this study was therefore, to identify novel histopathological prognostic markers of metastasis risk through exhaustive computational image analysis of 80 size and shape subsets of epithelial clusters in breast tumors. The group of 102 patients had a follow-up median of 12.3 years, without lymph node spread and systemic treatments. Epithelial cells were stained by the AE1/AE3 pan-cytokeratin antibody cocktail. The size and shape subsets of the stained epithelial cell clusters were defined in each image by use of the circularity and size filters and analyzed for prognostic performance. Epithelial areas with the optimal prognostic performance were uniformly small and round and could be recognized as individual epithelial cells scattered in tumor stroma. Their count achieved an area under the receiver operating characteristic curve (AUC) of 0.82, total area (AUC = 0.77), average size (AUC = 0.63), and circularity (AUC = 0.62). In conclusion, by use of computational image analysis as a hypothesis-free discovery tool, this study reveals the histomorphological marker with a high prognostic value that is simple and therefore easy to quantify by visual microscopy.

Cancer risk prognosis could improve patient survival through early personalized treatment decisions. This is the first systematic analysis of the spatial and prognostic distribution of different pan cytokeratin immunostaining intensities in breast tumors. The prognostic model included 102 breast carcinoma patients, with distant metastasis occurrence as the endpoint. We segmented the full intensity range (0–255) of pan cytokeratin digitized immunostaining into seven discrete narrow grey level ranges: 0–130, 130–160, 160–180, 180–200, 200–220, 220–240, and 240–255. These images were subsequently examined by 33 major (GLCM), fractal and first-order statistics computational analysis features. Interestingly, while moderate intensities were strongly associated with metastasis outcome, high intensities of pan cytokeratin immunostaining provided no prognostic value even after an exhaustive computational analysis. The intense pan cytokeratin immunostaining was also relatively rare, suggesting the low differentiation state of epithelial cells. The observed variability in immunostaining intensities highlighted the intratumoral heterogeneity of the malignant cells and its association with a poor disease outcome. The prognostic importance of the moderate intensity range established by complex computational morphology analyses was supported by simple measurements of its immunostaining area which was associated with favorable disease outcome. This study reveals intratumoral heterogeneity of the pan cytokeratin immunostaining together with the prognostic evaluation and spatial distribution of its discrete intensities.

Background/Objectives: Gamma knife radiosurgery (GKRS) is widely performed as an adjuvant management of patients with residual or recurrent pituitary adenoma (PA). However, the variability in the tumor volume response to GKRS emphasizes the need for reliable predictors of treatment outcomes. The application of radiomics, an analytical approach for quantitative imaging, remains unexplored in predicting treatment responses for PAs. This study aimed to pioneer the use of radiomic MRI analysis to predict the volumetric response of PA to GKRS. Methods: This retrospective observational cohort study involved 81 patients who underwent GKRS for PA. Pre-treatment 3-Tesla MRI scans were used to extract radiomic features capturing the intensity, shape, and texture of the tumors. Radiomic signatures were generated using the least absolute shrinkage and selection operator (LASSO) for feature selection, in conjunction with several classifiers: random forest, naïve Bayes, kNN, logistic regression, neural network, and SVM. Results: The models demonstrated predictive performance in the test folds, with AUC values ranging from 0.759 to 0.928 and R² values between 0.272 and 0.665. Single-sequence T1w, dual-sequence T1w + CE-T1w, and multi-modality including clinicopathological (CP) parameters (CP + T1w + CE-T1w) achieved rather similar prognostic performance in the test folds, with respective AUCs of 0.928, 0.899, and 0.909. All these radiomics models significantly outperformed a benchmark model involving only CP features (AUC = 0.846). Conclusions: This study represents a radiomic analysis focused on predicting the volume response of PAs to GKRS to facilitate treatment individualization. The developed MRI-based radiomics models exhibited superior classification performance compared with the benchmark model composed solely of standard clinicopathological parameters.

The striatum (neostriatum) is one of the principal constituents of the basal nuclei. It is a complex structure which consists of a dorsal and the ventral components. According to the spine distribution and their density, neurons of the human striatum can be classified into two main types: spiny and aspiny cells. Further classification recognizes two groups of spiny, and three groups of aspiny neurons. The goal of this study was to analyze different morphometric properties of the digital images of the group IV and group V aspiny neurons, from the dorsal striatum of both cerebral hemispheres. In this study, a total of 175 two-dimensional images of aspiny neurons were analyzed. Image reconstruction and measurement was performed with the specialized, public software Image J. Four parameters of standard fractal analysis were quantified from these binary images. In addition, five textural parameters were obtained by analyzing grayscale images of the entire neuron. Results of both analyses show that six of nine parameters differed between the group IV and group V aspiny neurons. Moreover, in both groups of neurons, one parameter of the fractal and three of the texture analyses differed between the putamen and the caudate nucleus neurons. Thus, this study corroborates previous classification of aspiny neurons. Although they belong to the same aspiny group, different type of cells can qualify nerve signals in their own way. Therefore, this study supports the hypothesis that neuronal morphology differences can reflect their functional diversity and their role in communication.

Purpose: Gamma Knife radiosurgery (GKRS) is widely performed as an adjuvant management of patients with residual or recurrent pituitary adenoma (PA). However, the variability in tumor volume response to GKRS emphasizes the need for reliable predictors of treatment outcomes. The application of radiomics, an analytical approach for quantitative imaging, remains unexplored in predicting treatment responses for PAs. This study aims to pioneer the use of radiomic MRI analysis to predict the volumetric response of PA to GKRS. Approach: This retrospective observational cohort study involved 81 patients who underwent GKRS for PA. Pre-treatment 3-Tesla MRI scans were used to extract radiomic features capturing the intensity, shape, and texture of the tumors. Radiomic signatures were generated using the least absolute shrinkage and selection operator (LASSO) for feature selection, in conjunction with several classifiers: random forest, naïve Bayes, kNN, logistic regression, neural network and SVM. Results: The models demonstrated predictive performance in the test folds with AUC values ranging from 0.759 to 0.928 and R2 values between 0.272 and 0.665. Single-sequence T1w, dual-sequence T1w+CE-T1w and multi-modality including clinicopathological (CP) parameters (CP+T1w+CE-T1w) achieved rather similar prognostic performance in test folds, with respective AUCs of 0.928, 0.899, and 0.909. All these radiomics models significantly outperformed a benchmark model involving only CP features (AUC=0.846). Conclusion: This study represents a radiomic analysis focused on predicting the volume response of PAs to GKRS to facilitate treatment individualization. The developed MRI-based radiomics models exhibited superior classification performance compared to the benchmark model composed solely of standard clinicopathological parameters.

Background: This study aimed to develop a fully nested, information leakage-free machine-learning workflow to predict the volumetric response of meningioma to Gamma Knife radiosurgery (GKRS) from pre-treatment MRI and to compare the predictive value of radiomic, fractal, lacunarity and clinical/radiosurgical features. GKRS is widely used for treating meningiomas because of its high precision and efficacy. Variability in tumor volumetric response highlights the need for reliable predictors of treatment outcome. Methods: This retrospective cohort study included 204 patients treated with GKRS for grade I meningioma. Radiomic, fractal and lacunarity features were extracted from pre-treatment CE-T1w 3-Tesla MRIs. Feature signatures were generated using a machine-learning workflow incorporating five feature selectors based on a consensus principle to reduce spurious feature selection, followed by five classifiers to predict binary outcome. Results: The models demonstrated consistent predictive performance in the test folds, with AUC values from 0.77 to 0.84. Supplementing radiomic features with clinical, fractal or lacunarity features did not improve predictive performance. Conclusions: Radiomic features showed the strongest predictive value for meningioma volumetric response to GKRS. Darker intratumoral intensity values were associated with a favorable volumetric response, possibly reflecting biologically less active tumor regions. The supplied code enables individual-level prediction for newly encountered patients.