Reclassifying stroke lesion anatomy

Anna K Bonkhoff,Tianbo Xu,Amy Nelson,Robert Gray,Ashwani Jha,Jorge Cardoso,Sebastien Ourselin,Geraint Rees,Hans Rolf Jäger,Parashkev Nachev

doi:10.1016/j.cortex.2021.09.007

Anna K Bonkhoff, Tianbo Xu + Show 8 more

Open Access

https://doi.org/10.1016/j.cortex.2021.09.007

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Abstract

Cognitive and behavioural outcomes in stroke reflect the interaction between two complex anatomically-distributed patterns: the functional organization of the brain and the structural distribution of ischaemic injury. Conventional outcome models—for individual prediction or population-level inference—commonly ignore this complexity, discarding anatomical variation beyond simple characteristics such as lesion volume. This sets a hard limit on the maximum fidelity such models can achieve. High-dimensional methods can overcome this problem, but only at prohibitively large data scales. Drawing on one of the largest published collections of anatomically-registered imaging of acute stroke—N = 1333—here we use non-linear dimensionality reduction to derive a succinct latent representation of the anatomical patterns of ischaemic injury, agglomerated into 21 distinct intuitive categories. We compare the maximal predictive performance it enables against both simpler low-dimensional and more complex high-dimensional representations, employing multiple empirically-informed ground truth models of distributed structure–outcome relationships. We show our representation sets a substantially higher ceiling on predictive fidelity than conventional low-dimensional approaches, but lower than that achievable within a high-dimensional framework. Where descriptive simplicity is a necessity, such as within clinical care or research trials of modest size, the representation we propose arguably offers a favourable compromise of compactness and fidelity.

Highlights

Stroke is remarkable in the wide diversity of its cognitive and behavioural manifestations and the difficulty of predicting them from the contemporaneous clinical picture alone(Boyd et al., 2017; Stinear, 2017; Ward, 2017)
The first is the functional anatomy of the brain focal ischaemic injury definitionally disrupts, comprehensively established to be highly complex and remarkably consistent across individuals: Journal Pre-proof meta-analytic imaging databases would otherwise be filled with noise, not generalisable clusters of coherent activation (Biswal et al, 2010; Eickhoff et al, 2018; Glasser et al, 2016)
We identified a set of 1333 patients admitted between 2001 and 2014 to University College London Hospitals (UCLH) with a clinical diagnosis of acute ischaemic stroke confirmed by diffusion weighted imaging (DWI)

Summary

Introduction

Stroke is remarkable in the wide diversity of its cognitive and behavioural manifestations and the difficulty of predicting them from the contemporaneous clinical picture alone(Boyd et al., 2017; Stinear, 2017; Ward, 2017) This cardinal aspect impedes the management of individual patients, the identification of protective or exacerbating factors in the population, and the quantification of treatment doses and effects. Were this heterogeneity biologically impossible to capture, we could do no more than to accept it as an unalterable fact of life. Since our knowledge of the functional anatomy of the brain depends to a great extent on the study of the functional consequences of stroke (Adolphs, 2016; Damasio & Damasio, 1989; Rorden & Karnath, 2004), the second of these characteristics is arguably of prior importance, and is our specific concern here

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