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Precision medicine promises better healthcare delivery by improving clinical practice. Using evidencebased substratification of patients, the objective is to achieve better prognosis, diagnosis, and treatment that will transform existing clinical pathways toward optimizing care for the specific needs of each patient. The wealth of today's healthcare data, often characterized as big data, provides invaluable resources toward new knowledge discovery that has the potential to advance precision medicine. The latter requires interdisciplinary efforts that will capitalize the information, know-how, and medical data of newly formed groups fusing different backgrounds and expertise. The objective of this paper is to provide insights with respect to the state-of-the-art research in precision medicine. More specifically, our goal is to highlight the fundamental challenges in emerging fields of radiomics and radiogenomics by reviewing the case studies of Cancer and Alzheimer's disease, describe the computational challenges from a big data analytics perspective, and discuss standardization and open data initiatives that will facilitate the adoption of precision medicine methods and practices.

Alzheimer's disease (AD) brain magnetic resonance imaging (MRI) biomarkers based on larger-scale tissue neurodegeneration changes, such as atrophy, are currently widely used. Texture analysis evaluates the statistical properties of the tissue image quantitatively; therefore, it could detect smaller-scale changes of neurodegeneration. Entorhinal cortex is the first region affected, and no study has investigated texture analysis on this region before. This study aims to differentiate AD patients from Normal Control (NC) and Mild Cognitive Impairment (MCI) subjects using entorhinal cortex texture features. Furthermore, it was evaluated whether texture has association to MCI beyond that of volume, to evaluate if atrophy development may precede. Texture features were extracted from 194 NC, 200 MCI, 84 MCI who converted to AD (MCIc), and 130 AD subjects. Receiving operating characteristic curves determined the performance of the various features in discriminating the groups, and a predictive model was used to predict conversion of MCIc subjects to AD. An area under the curve (AUC) of 0.872, 0.710, 0.730, and 0.764 was seen between NC vs. AD, NC vs. MCI, MCI vs. MCIc, and MCI vs. AD subjects, respectively. Including entorhinal cortex volume improved the AUCs to 0.914, 0.740, 0.756, and 0.780, respectively. For the disease prediction, binary logistic regression was applied on five randomly selected test groups and achieved on average AUC's of 0.760 and 0.764 on the training and validation cohorts, respectively. Entorhinal cortex texture features were significantly different between the four groups and in many cases provided better results compared to other methods such as volumetry.

Hippocampal and entorhinal cortex as scanned in Magnetic Resonance Imaging (MRI), are two of the most commonly used Regions of Interest (ROIs) for the assessment of Alzheimer's disease (AD). Both structures are used for the classification between Normal Controls (NC), Mild Cognitive Impairment (MCI) and AD subjects and for the disease prognosis.The objective of this study was to evaluate how the volume of these two structures changes between the following groups: NC vs AD, NC vs MCI, MCI vs MCI converters (MCIc -subjects who had converted to AD within 48 months), and AD vs MCIc subjects. Both structures were significantly reduced in volume for MCIc and AD subjects compared to NC. For both MCI and MCIc groups, the atrophy rate was correlated for both structures. In AD subjects, entorhinal cortex was more affected by atrophy. In conclusion, structural MRI and volumetric measurements of the hippocampus and entorhinal cortex can be used as early signs for the assessment of AD, and this is in agreement with previous studies.

IntroductionAlzheimer’s disease (AD) even nowadays remains a complex neurodegenerative disease and its diagnosis relies mainly on cognitive tests which have many limitations. On the other hand, qualitative imaging will not provide an early diagnosis because the radiologist will perceive brain atrophy on a late disease stage. Therefore, the main objective of this study is to investigate the necessity of quantitative imaging in the assessment of AD by using machine learning (ML) methods. Nowadays, ML methods are used to address high dimensional data, integrate data from different sources, model the etiological and clinical heterogeneity, and discover new biomarkers in the assessment of AD.MethodsIn this study radiomic features from both entorhinal cortex and hippocampus were extracted from 194 normal controls (NC), 284 mild cognitive impairment (MCI) and 130 AD subjects. Texture analysis evaluates statistical properties of the image intensities which might represent changes in MRI image pixel intensity due to the pathophysiology of a disease. Therefore, this quantitative method could detect smaller-scale changes of neurodegeneration. Then the radiomics signatures extracted by texture analysis and baseline neuropsychological scales, were used to build an XGBoost integrated model which has been trained and integrated.ResultsThe model was explained by using the Shapley values produced by the SHAP (SHapley Additive exPlanations) method. XGBoost produced a f1-score of 0.949, 0.818, and 0.810 between NC vs. AD, MC vs. MCI, and MCI vs. AD, respectively.DiscussionThese directions have the potential to help to the earlier diagnosis and to a better manage of the disease progression and therefore, develop novel treatment strategies. This study clearly showed the importance of explainable ML approach in the assessment of AD.