Abstract

We explored the performance of structure-based computational analysis in four neurodegenerative conditions [Ataxia (AT, n = 16), Huntington's Disease (HD, n = 52), Alzheimer's Disease (AD, n = 66), and Primary Progressive Aphasia (PPA, n = 50)], all characterized by brain atrophy. The independent variables were the volumes of 283 anatomical areas, derived from automated segmentation of T1-high resolution brain MRIs. The segmentation based volumetric quantification reduces image dimensionality from the voxel level [on the order of (106)] to anatomical structures [(102)] for subsequent statistical analysis. We evaluated the effectiveness of this approach on extracting anatomical features, already described by human experience and a priori biological knowledge, in specific scenarios: (1) when pathologies were relatively homogeneous, with evident image alterations (e.g., AT); (2) when the time course was highly correlated with the anatomical changes (e.g., HD), an analogy for prediction; (3) when the pathology embraced heterogeneous phenotypes (e.g., AD) so the classification was less efficient but, in compensation, anatomical and clinical information were less redundant; and (4) when the entity was composed of multiple subgroups that had some degree of anatomical representation (e.g., PPA), showing the potential of this method for the clustering of more homogeneous phenotypes that can be of clinical importance. Using the structure-based quantification and simple linear classifiers (partial least square), we achieve 87.5 and 73% of accuracy on differentiating AT and pre-symptomatic HD patents from controls, respectively. More importantly, the anatomical features automatically revealed by the classifiers agreed with the patterns previously described on these pathologies. The accuracy was lower (68%) on differentiating AD from controls, as AD does not display a clear anatomical phenotype. On the other hand, the method identified PPA clinical phenotypes and their respective anatomical signatures. Although most of the data are presented here as proof of concept in simulated clinical scenarios, structure-based analysis was potentially effective in characterizing phenotypes, retrieving relevant anatomical features, predicting prognosis, and aiding diagnosis, with the advantage of being easily translatable to clinics and understandable biologically.

Highlights

  • A longtime dream of clinicians is to use computational tools for aiding decisions

  • This study focused on the brain MRIs of patients with these neurodegenerative conditions: Ataxia (AT), Huntington’s Disease (HD), Alzheimer’s Disease (AD), and Primary Progressive Aphasia (PPA)

  • We showed the potential of the structurebased analysis on characterization and classification (1) when pathologies were relatively homogeneous, with evident image alterations (e.g., Ataxias); (2) when the time course was highly correlated with the anatomical changes (e.g., HD), an analogy for prediction; (3) when the pathology embraced heterogeneous phenotypes (e.g., AD) so the classification was less efficient but, in compensation, anatomical and clinical information were less redundant; and (4) when the entity was composed of multiple subgroups that had some degree of anatomical representation (e.g., Primary Progressive Aphasia), showing the potential of this method for the clustering of more homogeneous phenotypes that can be of clinical importance

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Summary

Introduction

A longtime dream of clinicians is to use computational tools for aiding decisions. Like using the spelling and grammar checkers when writing a text or Google for searching, clinical computational tools would neither define purposes nor change goals, but add a higher level of quality and speed to the results. There are three must-haves for computational-aid tools: speed, automation, and, efficacy. The development of such tools for medical records and imaging, in particular, is extremely complex, involving knowledge in multiple domains. The key to translating the computational models to radiological practice is to resolve the so-called semantic gap: “the differences between image similarity on the high level of human perception and the low level of a few numbers” (Depeursinge et al, 2011). Three basic steps are involved: precise quantification, optimal feature selection and combination, and, eventually, meaningful applications and testing

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