MRI's transverse relaxation time (T2) is sensitive to tissues' composition and pathological state. While variations in T2 values can be used as clinical biomarkers, it is challenging to quantify this parameter in vivo due to the complexity of the MRI signal model, differences in protocol implementations, and hardware imperfections. Herein, we provide a detailed analysis of the echo modulation curve (EMC) platform, offering accurate and reproducible mapping of T2 values, from 2D multi‐slice multi‐echo spin‐echo (MESE) protocols. Computer simulations of the full Bloch equations are used to generate an advanced signal model, which accounts for stimulated echoes and transmit field (B1+) inhomogeneities. In addition to quantifying T2 values, the EMC platform also provides proton density (PD) maps, and fat‐water fraction maps. The algorithm's accuracy, reproducibility, and insensitivity to T1 values are validated on a phantom constructed by the National Institute of Standards and Technology and on in vivo human brains. EMC‐derived T2 maps show excellent agreement with ground truth values for both in vitro and in vivo models. Quantitative values are accurate and stable across scan settings and for the physiological range of T2 values, while showing robustness to main field (B0) inhomogeneities, to variations in T1 relaxation time, and to magnetization transfer. Extension of the algorithm to two‐component fitting yields accurate fat and water T2 maps along with their relative fractions, similar to a reference three‐point Dixon technique. Overall, the EMC platform allows to generate accurate and stable T2 maps, with a full brain coverage using a standard MESE protocol and at feasible scan times. The utility of EMC‐based T2 maps was demonstrated on several clinical applications, showing robustness to variations in other magnetic properties. The algorithm is available online as a full stand‐alone package, including an intuitive graphical user interface.

Cutaneous melanoma tumors are heterogeneous and show diverse responses to treatment. Identification of robust molecular biomarkers for classifying melanoma tumors into clinically distinct and homogenous subtypes is crucial for improving the diagnosis and treatment of the disease. In this study, we present a classification of melanoma tumors into four subtypes with different survival profiles based on three distinct gene expression signatures: keratin, immune, and melanogenesis. The melanogenesis expression pattern includes several genes that are characteristic of the melanosome organelle and correlates with worse survival, suggesting the involvement of melanosomes in melanoma aggression. We experimentally validated the secretion of melanosomes into surrounding tissues by melanoma tumors, which potentially affects the lethality of metastasis. We propose a simple molecular decision tree classifier for predicting a tumor’s subtype based on representative genes from the three identified signatures. Key predictor genes were experimentally validated on melanoma samples taken from patients with varying survival outcomes. Our three-pattern approach for classifying melanoma tumors can contribute to advancing the understanding of melanoma variability and promote accurate diagnosis, prognostication, and treatment.

BackgroundAnalysis of large genomic datasets along with their accompanying clinical information has shown great promise in cancer research over the last decade. Such datasets typically include thousands of samples, each measured by one or several high-throughput technologies (‘omics’) and annotated with extensive clinical information. While instrumental for fulfilling the promise of personalized medicine, the analysis and visualization of such large datasets is challenging and necessitates programming skills and familiarity with a large array of software tools to be used for the various steps of the analysis.ResultsWe developed PROMO (Profiler of Multi-Omic data), a friendly, fully interactive stand-alone software for analyzing large genomic cancer datasets together with their associated clinical information. The tool provides an array of built-in methods and algorithms for importing, preprocessing, visualizing, clustering, clinical label enrichment testing, and survival analysis that can be performed on a single or multi-omic dataset. The tool can be used for quick exploration and stratification of tumor samples taken from patients into clinically significant molecular subtypes. Identification of prognostic biomarkers and generation of simple subtype classifiers are additional important features. We review PROMO’s main features and demonstrate its analysis capabilities on a breast cancer cohort from TCGA.ConclusionsPROMO provides a single integrated solution for swiftly performing a complete analysis of cancer genomic data for subtype discovery and biomarker identification without writing a single line of code, and can, therefore, make the analysis of these data much easier for cancer biologists and biomedical researchers. PROMO is freely available for download at http://acgt.cs.tau.ac.il/promo/.

Purpose: Multicomponent analysis of MRI T 2 relaxation time (mcT 2 ) is commonly used for estimating myelin content by separating the signal at each voxel into its underlying distribution of T 2 values. This voxel-based approach is challenging due to the large ambiguity in the multi-T 2 space and the low SNR of MRI signals. Herein, we present a data-driven mcT 2 analysis, which utilizes the statistical strength of identifying spatially global mcT 2 motifs in white matter segments before deconvolving the local signal at each voxel.Methods: Deconvolution is done using a tailored optimization scheme, which incorporates the global mcT 2 motifs without additional prior assumptions regarding the number of microscopic components. The end results of this process are voxel-wise myelin water fraction maps. Results: Validations are shown for computer-generated signals, uniquely designed subvoxel mcT 2 phantoms, and in vivo human brain. Results demonstrated excellent fitting accuracy, both for the numerical and the physical mcT 2 phantoms, exhibiting excellent agreement between calculated myelin water fraction and ground truth. Proof-of-concept in vivo validation is done by calculating myelin water fraction maps for white matter segments of the human brain. Interscan stability of myelin water fraction values was also estimated, showing good correlation between scans. Conclusion:We conclude that studying global tissue motifs prior to performing voxel-wise mcT 2 analysis stabilizes the optimization scheme and efficiently overcomes the ambiguity in the T 2 space. This new approach can improve myelin water imaging and the investigation of microstructural compartmentation in general.

BackgroundAnalysis of large genomic datasets along with their accompanying clinical information has shown great promise in cancer research over the last decade. Such datasets typically include thousands of samples, each measured by one or several high-throughput technologies ('omics') and annotated with extensive clinical information. While instrumental for fulfilling the promise of personalized medicine, the analysis and visualization of such large datasets is challenging and necessitates programming skills and familiarity with a large array of software tools to be used for the various steps of the analysis. ResultsWe developed PROMO (Profiler of Multi-Omic data), a friendly, fully interactive stand-alone software for analyzing large genomic cancer datasets together with their associated clinical information. The tool provides an array of built-in methods and algorithms for importing, preprocessing, visualizing, clustering, clinical label enrichment testing and survival analysis that can be performed on a single or multi-omic dataset. The tool can be used for quick exploration and for stratification of tumor samples taken from patients into clinically significant molecular subtypes. Identification of prognostic biomarkers and generation of simple subtype classifiers are additional important features. We review PROMO's main features and demonstrate its analysis capabilities on a breast cancer cohort from TCGA. ConclusionsPROMO provides a single integrated solution for swiftly performing a complete analysis of cancer genomic data for subtype discovery and biomarker identification without writing a single line of code, and can, therefore, make the analysis of these data much easier for cancer biologists and biomedical researchers.PROMO is freely available for download at http://acgt.cs.tau.ac.il/promo/.