A New Mutual Information based Similarity Measure for Medical Image Registration

Medical image registration (IR) is the systematic process of aligning spate images, often involving different modalities with common reference framework, so complementary information can be combined and compared. This paper presents a new similarity measure which uses Expectation Maximization for Principal Component Analysis allied with mutual information (EMPCA-MI) for medical IR. The new measure has been analysed on multimodal, three band magnetic resonance images (MRI) T1, T2 and PD weighted, in the presence of both intensity non-uniformities (INU) and noise. Both quantitative and qualitative experimental results clearly demonstrate both improved robustness and lower computational complexity of the new EMPCA-MI paradigm compared with existing MI-based similarity measures, for various MRI test datasets

Whole blood methylome-derived features to discriminate endocrine hypertension

BACKGROUND Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. RESULTS Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods-Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine-predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. CONCLUSIONS The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder

Efficient Image Registration using Fast Principal Component Analysis

Incorporating spatial features with mutual information (MI) has demonstrated superior image registration performance compared with traditional MI-based methods, particularly in the presence of noise and intensity non-uniformities (INU). This paper presents a new efficient MI-based similarity measure which applies Expectation Maximisation for Principal Component Analysis (EMPCA-MI), to afford significantly lower computational complexity, while providing analogous image registration performance with other feature-based MI solutions. Experimental analysis corroborates both the improved robustness and faster runtimes of EMPCA-MI, for different test datasets containing both INU and noise artefacts

Multimodal retinal image registration using a fast principal component analysis hybrid-based similarity measure

Multimodal retinal images (RI) are extensively used for analysing various eye diseases and conditions such as myopia and diabetic retinopathy. The incorporation of either two or more RI modalities provides complementary structure information in the presence of non-uniform illumination and low-contrast homogeneous regions. It also presents significant challenges for retinal image registration (RIR). This paper investigates how the Expectation Maximization for Principal Component Analysis with Mutual Information (EMPCA-MI) algorithm can effectively achieve multimodal RIR. This iterative hybrid-based similarity measure combines spatial features with mutual information to provide enhanced registration without recourse to either segmentation or feature extraction. Experimental results for clinical multimodal RI datasets comprising colour fundus and scanning laser ophthalmoscope images confirm EMPCA-MI is able to consistently afford superior numerical and qualitative registration performance compared with existing RIR techniques, such as the bifurcation structures method

Whole blood methylome-derived features to discriminate endocrine hypertension

Background: Arterial hypertension represents a worldwide health burden and a major risk factor for cardiovascular morbidity and mortality. Hypertension can be primary (primary hypertension, PHT), or secondary to endocrine disorders (endocrine hypertension, EHT), such as Cushing's syndrome (CS), primary aldosteronism (PA), and pheochromocytoma/paraganglioma (PPGL). Diagnosis of EHT is currently based on hormone assays. Efficient detection remains challenging, but is crucial to properly orientate patients for diagnostic confirmation and specific treatment. More accurate biomarkers would help in the diagnostic pathway. We hypothesized that each type of endocrine hypertension could be associated with a specific blood DNA methylation signature, which could be used for disease discrimination. To identify such markers, we aimed at exploring the methylome profiles in a cohort of 255 patients with hypertension, either PHT (n = 42) or EHT (n = 213), and at identifying specific discriminating signatures using machine learning approaches. Results: Unsupervised classification of samples showed discrimination of PHT from EHT. CS patients clustered separately from all other patients, whereas PA and PPGL showed an overall overlap. Global methylation was decreased in the CS group compared to PHT. Supervised comparison with PHT identified differentially methylated CpG sites for each type of endocrine hypertension, showing a diffuse genomic location. Among the most differentially methylated genes, FKBP5 was identified in the CS group. Using four different machine learning methods—Lasso (Least Absolute Shrinkage and Selection Operator), Logistic Regression, Random Forest, and Support Vector Machine—predictive models for each type of endocrine hypertension were built on training cohorts (80% of samples for each hypertension type) and estimated on validation cohorts (20% of samples for each hypertension type). Balanced accuracies ranged from 0.55 to 0.74 for predicting EHT, 0.85 to 0.95 for predicting CS, 0.66 to 0.88 for predicting PA, and 0.70 to 0.83 for predicting PPGL. Conclusions: The blood DNA methylome can discriminate endocrine hypertension, with methylation signatures for each type of endocrine disorder

Machine learning for classification of hypertension subtypes using multi-omics: a multi-centre, retrospective, data-driven study

Background: Arterial hypertension is a major cardiovascular risk factor. Identification of secondary hypertension in its various forms is key to preventing and targeting treatment of cardiovascular complications. Simplified diagnostic tests are urgently required to distinguish primary and secondary hypertension to address the current underdiagnosis of the latter. Methods: This study uses Machine Learning (ML) to classify subtypes of endocrine hypertension (EHT) in a large cohort of hypertensive patients using multidimensional omics analysis of plasma and urine samples. We measured 409 multi-omics (MOmics) features including plasma miRNAs (PmiRNA: 173), plasma catechol O-methylated metabolites (PMetas: 4), plasma steroids (PSteroids: 16), urinary steroid metabolites (USteroids: 27), and plasma small metabolites (PSmallMB: 189) in primary hypertension (PHT) patients, EHT patients with either primary aldosteronism (PA), pheochromocytoma/functional paraganglioma (PPGL) or Cushing syndrome (CS) and normotensive volunteers (NV). Biomarker discovery involved selection of disease combination, outlier handling, feature reduction, 8 ML classifiers, class balancing and consideration of different age- and sex-based scenarios. Classifications were evaluated using balanced accuracy, sensitivity, specificity, AUC, F1, and Kappa score. Findings: Complete clinical and biological datasets were generated from 307 subjects (PA=113, PPGL=88, CS=41 and PHT=112). The random forest classifier provided ∼92% balanced accuracy (∼11% improvement on the best mono-omics classifier), with 96% specificity and 0.95 AUC to distinguish one of the four conditions in multi-class ALL-ALL comparisons (PPGL vs PA vs CS vs PHT) on an unseen test set, using 57 MOmics features. For discrimination of EHT (PA + PPGL + CS) vs PHT, the simple logistic classifier achieved 0.96 AUC with 90% sensitivity, and ∼86% specificity, using 37 MOmics features. One PmiRNA (hsa-miR-15a-5p) and two PSmallMB (C9 and PC ae C38:1) features were found to be most discriminating for all disease combinations. Overall, the MOmics-based classifiers were able to provide better classification performance in comparison to mono-omics classifiers. Interpretation: We have developed a ML pipeline to distinguish different EHT subtypes from PHT using multi-omics data. This innovative approach to stratification is an advancement towards the development of a diagnostic tool for EHT patients, significantly increasing testing throughput and accelerating administration of appropriate treatment. Funding: European Union's Horizon 2020 Research and Innovation Programme under Grant Agreement No. 633983, Clinical Research Priority Program of the University of Zurich for the CRPP HYRENE (to Z.E. and F.B.), and Deutsche Forschungsgemeinschaft (CRC/Transregio 205/1)

Robust image registration using adaptive expectation maximisation based PCA

Images having either the same or different modalities can be aligned using the systematic process of image registration. Inherent image characteristics including intensity non-uniformities in magnetic resonance images and large homogeneous non-vascular regions in retinal and other generic image types however, pose a significant challenge to their registration. This paper presents an adaptive expectation maximisation for principal component analysis with mutual information (aEMPCA-MI) similarity measure for image registration. It introduces a novel iterative process to adaptively select the most significant principal components using Kaiser rule and applies 4-pixel connectivity for feature extraction together with Wichard's bin size selection in calculating the MI. Both quantitative and qualitative results on a diverse range of image datasets, conclusively demonstrate the superior image registration performance of aEMPCA-MI compared with existing MI-based similarity measures