TY - JOUR
T1 - Quantifying the impact of shape uncertainty on predicted arrhythmias
AU - Corrado, Cesare
AU - Roney, Caroline
AU - Razeghi, Orod
AU - Solis Lemus, Jose Alonso
AU - Coveney, Sam
AU - Sim, Iain
AU - Williams, Steven
AU - O'Neill, Mark
AU - Wilkinson, Richard D.
AU - Clayton, Richard H
AU - Niederer, Steven
N1 - Funding Information:
This work was supported by the EPSRC, United Kingdom ( EP/P101268X/1 ), the Wellcome Centre, United Kingdom , and the Department of Health via the National Institute for Health Research (NIHR), United Kingdom comprehensive Biomedical Research Centre award to Guy’s & St Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust. CHR acknowledges a Medical Research Council Skills Development Fellowship, United Kingdom ( MR/S015086/1 ). SEW is supported by the British Heart Foundation, United Kingdom ( FS/20/26/34952 ) and the British Heart Foundation Centre for Research Excellence at the University of Edinburgh ( RE/18/5/34216 ).
Funding Information:
This work was supported by the EPSRC, United Kingdom (EP/P101268X/1), the Wellcome Centre, United Kingdom, and the Department of Health via the National Institute for Health Research (NIHR), United Kingdom comprehensive Biomedical Research Centre award to Guy's & St Thomas’ NHS Foundation Trust in partnership with King's College London and King's College Hospital NHS Foundation Trust. CHR acknowledges a Medical Research Council Skills Development Fellowship, United Kingdom (MR/S015086/1). SEW is supported by the British Heart Foundation, United Kingdom (FS/20/26/34952) and the British Heart Foundation Centre for Research Excellence at the University of Edinburgh (RE/18/5/34216).
Publisher Copyright:
© 2023 The Authors
PY - 2023/2
Y1 - 2023/2
N2 - Background.: Personalised computer models are increasingly used to diagnose cardiac arrhythmias and tailor treatment. Patient-specific models of the left atrium are often derived from pre-procedural imaging of anatomy and fibrosis. These images contain noise that can affect simulation predictions. There are few computationally tractable methods for propagating uncertainties from images to clinical predictions. Method.: We describe the left atrium anatomy using our Bayesian shape model that captures anatomical uncertainty in medical images and has been validated on 63 independent clinical images. This algorithm describes the left atrium anatomy using N
modes=15 principal components, capturing 95% of the shape variance and calculated from 70 clinical cardiac magnetic resonance (CMR) images. Latent variables encode shape uncertainty: we evaluate their posterior distribution for each new anatomy. We assume a normally distributed prior. We use the unscented transform to sample from the posterior shape distribution. For each sample, we assign the local material properties of the tissue using the projection of late gadolinium enhancement CMR (LGE-CMR) onto the anatomy to estimate local fibrosis. To test which activation patterns an atrium can sustain, we perform an arrhythmia simulation for each sample. We consider 34 possible outcomes (31 macro-re-entries, functional re-entry, atrial fibrillation, and non-sustained arrhythmia). For each sample, we determine the outcome by comparing pre- and post-ablation activation patterns following a cross-field stimulus. Results.: We create patient-specific atrial electrophysiology models of ten patients. We validate the mean and standard deviation maps from the unscented transform with the same statistics obtained with 12,000 Monte Carlo (ground truth) samples. We found discrepancies <3% and <2% for the mean and standard deviation for fibrosis burden and activation time, respectively. For each patient case, we then compare the predicted outcome from a model built on the clinical data (deterministic approach) with the probability distribution obtained from the simulated samples. We found that the deterministic approach did not predict the most likely outcome in 80% of the cases. Finally, we estimate the influence of each source of uncertainty independently. Fixing the anatomy to the posterior mean and maintaining uncertainty in fibrosis reduced the prediction of self-terminating arrhythmias from ≃14% to ≃7%. Keeping the fibrosis fixed to the sample mean while retaining uncertainty in shape decreased the prediction of substrate-driven arrhythmias from ≃33% to ≃18% and increased the prediction of macro-re-entries from ≃54% to ≃68%. Conclusions.: We presented a novel method for propagating shape uncertainty in atrial models through to uncertainty in numerical simulations. The algorithm takes advantage of the unscented transform to compute the output distribution of the outcomes. We validated the unscented transform as a viable sampling strategy to deal with anatomy uncertainty. We then showed that the prediction computed with a deterministic model does not always coincide with the most likely outcome. Finally, we found that shape uncertainty affects the predictions of macro-re-entries, while fibrosis uncertainty affects the predictions of functional re-entries.
AB - Background.: Personalised computer models are increasingly used to diagnose cardiac arrhythmias and tailor treatment. Patient-specific models of the left atrium are often derived from pre-procedural imaging of anatomy and fibrosis. These images contain noise that can affect simulation predictions. There are few computationally tractable methods for propagating uncertainties from images to clinical predictions. Method.: We describe the left atrium anatomy using our Bayesian shape model that captures anatomical uncertainty in medical images and has been validated on 63 independent clinical images. This algorithm describes the left atrium anatomy using N
modes=15 principal components, capturing 95% of the shape variance and calculated from 70 clinical cardiac magnetic resonance (CMR) images. Latent variables encode shape uncertainty: we evaluate their posterior distribution for each new anatomy. We assume a normally distributed prior. We use the unscented transform to sample from the posterior shape distribution. For each sample, we assign the local material properties of the tissue using the projection of late gadolinium enhancement CMR (LGE-CMR) onto the anatomy to estimate local fibrosis. To test which activation patterns an atrium can sustain, we perform an arrhythmia simulation for each sample. We consider 34 possible outcomes (31 macro-re-entries, functional re-entry, atrial fibrillation, and non-sustained arrhythmia). For each sample, we determine the outcome by comparing pre- and post-ablation activation patterns following a cross-field stimulus. Results.: We create patient-specific atrial electrophysiology models of ten patients. We validate the mean and standard deviation maps from the unscented transform with the same statistics obtained with 12,000 Monte Carlo (ground truth) samples. We found discrepancies <3% and <2% for the mean and standard deviation for fibrosis burden and activation time, respectively. For each patient case, we then compare the predicted outcome from a model built on the clinical data (deterministic approach) with the probability distribution obtained from the simulated samples. We found that the deterministic approach did not predict the most likely outcome in 80% of the cases. Finally, we estimate the influence of each source of uncertainty independently. Fixing the anatomy to the posterior mean and maintaining uncertainty in fibrosis reduced the prediction of self-terminating arrhythmias from ≃14% to ≃7%. Keeping the fibrosis fixed to the sample mean while retaining uncertainty in shape decreased the prediction of substrate-driven arrhythmias from ≃33% to ≃18% and increased the prediction of macro-re-entries from ≃54% to ≃68%. Conclusions.: We presented a novel method for propagating shape uncertainty in atrial models through to uncertainty in numerical simulations. The algorithm takes advantage of the unscented transform to compute the output distribution of the outcomes. We validated the unscented transform as a viable sampling strategy to deal with anatomy uncertainty. We then showed that the prediction computed with a deterministic model does not always coincide with the most likely outcome. Finally, we found that shape uncertainty affects the predictions of macro-re-entries, while fibrosis uncertainty affects the predictions of functional re-entries.
KW - uncertainty quantification
KW - Cardiac models
KW - Atrial tachycardia
KW - Medical image processing
UR - http://www.scopus.com/inward/record.url?scp=85146056328&partnerID=8YFLogxK
U2 - 10.1016/j.compbiomed.2022.106528
DO - 10.1016/j.compbiomed.2022.106528
M3 - Article
SN - 0010-4825
VL - 153
JO - Computers in Biology and Medicine
JF - Computers in Biology and Medicine
M1 - 106528
ER -