Precision Modelling of Cortical Variation and its Association with Neurological/Psychiatric disease

Lead Research Organisation: King's College London
Department Name: Imaging & Biomedical Engineering

Abstract

The aim of this proposal is to develop a novel medical imaging support tool to significantly improve rates of detection, of types of subtle brain abnormality, which give rise to complex brain conditions. Specifically, we are seeking to develop tools that improve the accuracy with which we can compare brain scans across populations. This will make it much easier to tell the difference between healthy and atypical brains, or detect diseased tissue.

The reason that this is challenging is because brains are extremely complex, made of billions of cells, and each one can look very different. This makes it hard to build a single model of what "healthy" brains should look like, and as a result it becomes very difficult to spot evidence of disease.

These challenges mean that radiologists require years of experience, reviewing countless examples, before they can reliably spot subtle brain abnormalities, and even so, for diseases such as focal childhood epilepsies, up to 30% of cases evade detection. For similar reasons, automated tools often also struggle: appearance of scans varies so extensively that simplifying assumptions must be made leading to coarse solutions.

The largest assumption is that all brains share a common organisational blueprint, where areas of the brain responsible for different functions appear in the same order. Such that if each brain scan was a jigsaw, with each piece a region, the shapes might change but they would in go together in the same way. However, in reality brains vary topographically, which means that areas representing different functions (such as language) can swap location. Methods assuming otherwise end up comparing completely different areas of the brain across individuals. Each area may look very different, with different definitions of what is normal. As a result, this leads to confusion, limiting the ability of any method to detect signs of disease.

In the past, methods were particularly limited as they built their model of regional organisation based simply on patterns of brain folding. However, it turns out that shape is a fairly coarse and non-specific model of brain organisation, and that brains often have very different patterns of brain folding for the same functional region.

Recently we developed a novel open-access tool, which instead learns how to map brains onto a model which takes into account, not just shape but also function, and other aspects of brain organisation (Robinson Neuroimage 2014, 2018). This has led to new, more accurate, models of cortical organisation (Glasser Nature 2016) and development (Garcia PNAS 2018, O'Muircheartaigh Brain 2020) and improved understanding of the links between brain organisation and behaviour (Bijsterbosch Elife 2018).
Now we propose to extend this tool, to account for variation of brain shape and appearance in a way that reflects the natural variation seen from one individual to another. Rather than learn a single model of brain organisation we will learn a family of models (modes) that try to describe how our brains vary. These will capture all biologically relevant modes of variation, allowing individual brain scans to be compared, for a given location, only against others with a common organisational blueprint. In this way we will support much more detailed comparison, than was ever possible before.

We will validate the power of the approach through three studies: 1) finding the source of epileptic seizures in the brain (to support surgical planning); 2) predicting cognitive outcomes for babies with developmental brain conditions; 3) identifying biological markers in the brain that may help predict mental health conditions. Ultimately, these tools will support researchers, medical doctors and healthcare workers to build more sensitive predictive models, fine tuned to detect signs of abnormality within individual brains. This will improve screening detection rates and lead to more accurate diagnosis of all brain conditions.

Technical Summary

The purpose of this grant is to develop urgently needed new technologies for image processing of brain scans to support precise comparisons of populations of brain scans and sensitive localisation of pathologies within individual scans.

It is motivated by the fact that current methods for brain image analysis largely ignore considerable variation in brain shape and cortical organisation across individuals in order to deliver well-posed optimisations, which allow reliable but coarse scale comparisons of data across populations. Specifically, these compare brains through use of image registration algorithms which support smooth and invertible spatial mappings of all data into a global average space, where images may be directly compared. Alternative approaches, such as deep learning (which avoids this) require enormous data-sets, and return limited explainability (leaving ethical concerns over bias and generalisation).

The key problem with image registration to a single, global template is that this typically ignores subtle sources of individual variation leading to (in some circumstances very) low powered studies of complex phenomena. This is because there is nothing inherent in these algorithms constraining atypical variants of brain architecture to be in correspondence.

In this proposal, we therefore seek to develop new techniques for brain image registration which seek to learn all clinically or behaviourally relevant patterns of topographic variation, with the intent of matching these during alignment. In this way, images will be brought into much closer correspondence than possible before, allowing precision generative modelling of population variation for detection of cortical abnormalities in small populations. These frameworks will be used to test and validate development of novel explainable deep-learning frameworks.
 
Description OHBM Educational course
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
URL https://ww6.aievolution.com/hbm2401/index.cfm?do=ev.viewEv&ev=1539
 
Title Generative model of cortical neurodevelopment 
Description This is an AI model of healthy cortical neurodevelopment, trained on cortical surface data. It can be used to simulate how an preterm individual's brain should develop if it was healthy. A derived measure of deviation between simulated healthy scans and ground truth follow up scans improves the precision with which it is possible to predict cognitive outcomes of these individuals at 18 months. 
Type Of Material Computer model/algorithm 
Year Produced 2023 
Provided To Others? Yes  
Impact The paper describing this method is under revision for the journal Imaging Neuroscience An early version of this method was presented as an oral at the Medical Image Understanding and Analysis Conference (2022) 
URL https://github.com/Abdulah-Fawaz/continuous_cGAN
 
Title dHCP fetal cortical surface atlas 
Description Fetal brain surface atlas, weeks 21-36 of gestation, constructed using 242 in-utero scans from the fetal dHCP cohort. 
Type Of Material Database/Collection of data 
Year Produced 2023 
Provided To Others? Yes  
Impact Has been submitted to OHBM 2023 
URL https://gin.g-node.org/kcl_cdb/dhcp_fetal_brain_surface_atlas
 
Description Collaboration with Wash University St Louis (WashU) 
Organisation Washington University in St Louis
Country United States 
Sector Academic/University 
PI Contribution This is an intellectual collaboration involving our sharing of the software that is being developed
Collaborator Contribution WashU are sharing data and expertise.
Impact OHBM abstracts 2023: https://github.com/metrics-lab/Posters/blob/main/2023/OHBM/Guo_Uncovering-Folding-Hierarchical-Registration.pdf OHBM 2024 abstracts: Rosen Burke et al. Mapping evolutionary cortical expansion with anatomical MSM Yourong Guo et al. Uncovering the asymmetry of common temporal lobe folding variants
Start Year 2022
 
Title Geomorph 
Description An AI tool for learning spatial mappings between cortical surface feature sets 
Type Of Technology Software 
Year Produced 2023 
Open Source License? Yes  
Impact The resulting paper is under revision for Medical Image Analysis (IF 10.9) 
URL https://github.com/mohamedasuliman/GeoMorph
 
Title New MSM 
Description New MSM is a reimplementation of Multimodal Surface Matching (MSM) (Robinson et al. Neuroimage 2014,2018) a tool used for mapping cortical surface imaging feature sets into a common reference space such that features of cortical organisation may be directly compared across populations. MSM was fundamental to the HCP Multimodal parcellation (Glasser Nature 2016). However, the original implementation was extremely slow (90 mins). The new version of MSM runs in 2 mins. This is forming the basis of the groupwise registration framework which is central to the grant. 
Type Of Technology Software 
Year Produced 2023 
Open Source License? Yes  
Impact newMSM is yet to be fully rolled out but is being used by collaborators in Washu, Barcelona, Indiana and internally to speed up computation of big data analyses of brain imaging data. 
URL https://github.com/rbesenczi/newMSM
 
Title continuous_cGAN 
Description Builds generative models of cortical development and ageing from cortical imaging feature sets 
Type Of Technology Software 
Year Produced 2023 
Open Source License? Yes  
Impact Paper under revision for Imaging Neuroscience 
URL https://github.com/Abdulah-Fawaz/continuous_cGAN/blob/main/LICENSE