Dr. Neil Oxtoby | Mathematical Modelling and Analysis. Physicist turned Disease Progression Modeller.

AD/PD 2023 talk: SuStaIn in the A4 Study

Posted on 2023-03-15 | Leave a comment

I prerecorded the audio below (8 minutes) to go with these PDF slides for AD/PD 2023 in Gothenburg, Sweden.

Disease Progression Modelling on MRI data Identifies Subtypes with Cognitive Heterogeneity in A4 Study Preclinical Trial Cohort

TL;DR: We used SuStaIn to find MRI-based subtypes in the screening data of the A4 Study clinical trial (preclinical Alzheimer’s disease) and leveraged the ADNI observational dataset to link these subtypes to heterogeneous cognitive decline.

This could potentially wash out any treatment effect (if present) in the A4 study trial. This work was completed before the results of A4 were known.

AD/PD 2023 Talk

AD/PD 2023 Oxtoby slides Download

Relevant papers:

Full paper preprint: Shand et al., medRxiv 2023
SuStaIn original paper: Young et al., Nature Communications 2018
A4 Study: a4study.org

UCSD ADRC Neurodegeneration Seminar

Posted on 2022-12-06 | Leave a comment

It was my pleasure to present these slides remotely as part of the UCSD ADRC’s Neurodegeneration Seminar Series this morning (my evening!).

Thanks to Doug Galasko for the invitation.

20221206-UCSD_ADRC-Neurodegeneration_Seminar-Oxtoby Download

New paper on data-driven progression subtypes in Alzheimer’s disease

Posted on 2021-04-30 | Comments Off

Latest paper is an amazing collaboration led by the wonderful Jake Vogel that pulled together the largest database so far of tau PET imaging of Alzheimer’s pathology in the living brain, then unleashed Alex Young’s SuStaIn algorithm to discover four previously unknown/uncharacterised subtypes.

It turns out that these are quite common (as in not rare), and they have unique symptom profiles too.

https://www.nature.com/articles/s41591-021-01309-6

I could dig in, but here’s what Jake had to say on twitter:

Does Alzheimer’s disease pathology spread through the brain consistently across the population? We delve into this in our paper “Four distinct trajectories of tau deposition identified in Alzheimer’s disease”, now online at Nature Medicine. https://t.co/eNAZ63pe3z Thread below 1/
— Jake Vogel (@_JakeVogel_) April 29, 2021

Tau is one of the two pathologies that characterize Alzheimer’s disease (AD). Autopsy work suggests it spreads in a specific and highly compelling pattern, formalized into the Break staging system and used to stage tau pathology in AD. See https://t.co/hiKLt7hGY6. 2/ pic.twitter.com/y1LBXUIGPK
— Jake Vogel (@_JakeVogel_) April 29, 2021

@DrNeuroChic showed limbic-predominant and hippocampal-sparing patterns that deviated from the Break progression were not uncommon https://t.co/cznIUD1Pyp. @RikOssenkoppele showed that clinical variants of AD also have deviant patterns https://t.co/ZpM7Ugnayu. What gives? 3/ pic.twitter.com/QD6kh1O2DF
— Jake Vogel (@_JakeVogel_) April 29, 2021

Parsing AD heterogeneity in an unbiased manner has been challenging because overall severity is the greatest source of spatial variance. Alex Young created the SuStaIn algorithm https://t.co/txD9ivcTKC, which handles both pseudotemporal and spatial aspects of variation 4/ pic.twitter.com/RB1WiojfPc
— Jake Vogel (@_JakeVogel_) April 29, 2021

But this requires pretty large sample sizes. So, we got together with researchers at the @UCSFmac, @biofinder_study in Sweden, Gagnam Severance in Korea, AVID radiopharmaceuticals, + ADNI data to come up with over 1600 tau-PET scans. 1143 were used for analysis. 5/
— Jake Vogel (@_JakeVogel_) April 29, 2021

Applying SuStaIn to this dataset, we found four distinct spatiotemporal patterns, including limbic-predominant and MTL-sparing variants similar to those described by @DrNeuroChic, as well as posterior and lateral temporal subtypes resembling the clinical variants, PCA & lvPPA 6/ pic.twitter.com/HhgflhbyjP
— Jake Vogel (@_JakeVogel_) April 29, 2021

Each subtype was found in each of the five cohorts we studied. We then applied SuStaIn separately on another cohort, BioFINDER II, which used a totally different tau-PET radiotracer. Performing the analysis from scratch in this group, we found highly similar subtypes. 7/ pic.twitter.com/gMr4lGgShw
— Jake Vogel (@_JakeVogel_) April 29, 2021

The 4 subtypes differed in their clinical presentation, including in terms of age, likelihood of APOE4 allele carriage, and cognitive profiles. We found the posterior subtype to exhibit a slower rate of global decline, while the lateral temporal variant progressed faster. 8/ pic.twitter.com/HNvsmXRYsF
— Jake Vogel (@_JakeVogel_) April 29, 2021

Using network diffusion methods from our previous paper https://t.co/YLWgPETKd6, we found the tau-PET patterns of each of the 4 subtypes resembled a different temporal lobe network. Simulating diffusion through that network could recapitulate the subtype patterns observed. 9/ pic.twitter.com/tNdBtVslGE
— Jake Vogel (@_JakeVogel_) April 29, 2021

In all, we conclude that there may not be such an entity as “typical AD”, but rather that individuals with AD present with one of at least four different subtypes with distinct prognoses. In addition, younger age is associated with more severe subtype expression. /10 pic.twitter.com/GLAqtmjrst
— Jake Vogel (@_JakeVogel_) April 29, 2021

This latter point means clinical variants may just be extreme presentations of normally occurring AD subtypes. This idea is supported by recent work by @Colin__Groot from @RikOssenkoppele lab — see Figure 4 of https://t.co/NEKvdcFeY9 11/
— Jake Vogel (@_JakeVogel_) April 29, 2021

We are interested to see our findings validated by pathologists, and we would like to better characterize these subtypes. Will they respond differently to treatment? What does it mean about disease biology? Much work to be done. 12/
— Jake Vogel (@_JakeVogel_) April 29, 2021

We also had to cut a lot of words to fit the journal’s requirements, but see the original preprint for a much more in-depth discussion. https://t.co/GAeIiWOtvG /13
— Jake Vogel (@_JakeVogel_) April 29, 2021

This was an amazing collaboration by the research centers described above, plus us at @TheNeuro_MNI and the methodologists at UCL. Big thanks to Alex, @NeilOxtoby, @relajoie, @RikOssenkoppele, @OskarHansson9, @MedinYasser and many amazing of non-tweeps! /end
— Jake Vogel (@_JakeVogel_) April 29, 2021

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Vacancy: Research Assistant in Memory Clinic Image Computing

Posted on 2021-04-21 | Comments Off

Apply Here (closing date: 23 May 2021)

I have a vacancy for a post-Masters / pre-PhD level person interested in medical image (MRI) data wrangling and analysis, including computational modelling of neurological diseases like Alzheimer’s and Lewy Body Disease.

One important goal for the project is to use existing computational methods (from the POND group) to build a differential diagnosis tool for dementias, Specifically Alzheimer’s Disease vs Lewy body Dementia.

This is exciting for two reasons in particular: we are looking at real world data from individuals in the prodromal stage of dementia.

If you’re not quite ready for a PhD and are interested in medical image computing, this could be the role for you. The ideal candidate would have a background in computer science, physics, maths, medical image computing, or a related field.

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Tagged dementia, job, ucl, vacancy

NISOx talks

Posted on 2021-03-10 | Comments Off

I was invited to present today to the NeuroImaging Statistics Oxford (NISOx) reading group of Prof Thomas Nichols at the Oxford Big Data Institute.

I ended up giving two talks after my first talk (on TADPOLE Challenge) generated some interest in the event-based model!

Here are the slides:

Talk 1 Download

Talk 2 Download

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Rosetrees Interdisciplinary workshop on neurodegenerative diseases of the brain

Posted on 2021-02-11 | Comments Off

Many thanks to the organisers of the Rosetrees interdisciplinary workshop on neurodegenerative diseases of the brain yesterday (10 Feb, via Zoom).

I had a great time presenting my talk and discussing the physics of life, plus our work on disease progression modelling in the UCL POND group.

My slides are here:
Top-down and Bottom-up models of neurodegenerative disease progression

The recording of my talk is up on YouTube:
https://youtu.be/JdplymQmoHo?t=8177.

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CompAge 2020

Posted on 2020-09-01 | Comments Off

Here’s my poster:

http://neiloxtoby.com/work/wp-content/uploads/2020/09/35_Oxtoby.pdf

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AAIC 2020 presentations

Posted on 2020-07-29 | Comments Off

Here are my presentations from AAIC 2020:

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MRC-ULHA Zoom Seminar

Posted on 2020-05-13 | Comments Off

Thanks to folks in the UCL MRC Unit for Lifelong Health and Ageing (and colleagues beyond) for hosting me for a Zoom seminar today (13 May 2020).

I very much appreciate the questions, discussion, and enthusiasm for my research.

Special thanks to Sarah-Naomi James for inviting me!

Here are the slides: neiloxtoby.com/work/20200513-mrc_unit-seminar-lores

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CMIC seminar

Posted on 2020-01-16 | Comments Off

Thanks to colleagues in the UCL Centre for Medical Image Computing (CMIC) and Dementia Research Centre for turning out in force yesterday for my CMIC seminar (15 January 2020).

Looking forward to following up with new results as they come in now that my UKRI Future Leaders Fellowship has started!

Here are the slides: neiloxtoby.com/work/20200115-cmic_seminar

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