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Sébastien Ourselin

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23 papers
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23

AAAI Conference 2025 Conference Paper

Generative Medical Segmentation

  • Jiayu Huo
  • Xi Ouyang
  • Sébastien Ourselin
  • Rachel Sparks

Rapid advancements in medical image segmentation performance have been significantly driven by the development of Convolutional Neural Networks (CNNs) and Vision Transformers (ViTs). These models follow discriminative pixel-wise classification learning paradigm and often have limited ability to generalize across diverse medical imaging datasets. In this manuscript, we introduce Generative Medical Segmentation (GMS), a novel generative approach to perform image segmentation. GMS employs a robust pre-trained vision foundation model to extract latent representations for images and corresponding ground truth masks, followed by a lightweight model that learns a mapping function from the image to the mask in the latent space. Once trained, the model can generate estimated segmentation masks using the pre-trained vision foundation model to decode the predicted latent mask representation back into image space. The design of GMS leads to fewer trainable parameters in the model, reducing the risk of overfitting and enhancing its generalization capability. Our experimental analysis across five open-source datasets in different medical imaging domains demonstrates GMS outperforms existing discriminative and generative segmentation models. Furthermore, GMS is able to generalize well across datasets of the same imaging modality from different centers. Our experiments suggest GMS offers a scalable and effective solution for medical image segmentation.

ICRA Conference 2025 Conference Paper

SurgPLAN++: Universal Surgical Phase Localization Network for Online and Offline Inference

  • Zhen Chen 0018
  • Xingjian Luo
  • Jinlin Wu
  • Long Bai 0008
  • Zhen Lei 0001
  • Hongliang Ren 0001
  • Sébastien Ourselin
  • Hongbin Liu 0001

Surgical phase recognition is critical for assisting surgeons in understanding surgical videos. Existing studies focused more on online surgical phase recognition, by leveraging preceding frames to predict the current frame. Despite great progress, they formulated the task as a series of frame-wise classification, which resulted in a lack of global context of the entire procedure and incoherent predictions. Moreover, besides online analysis, accurate offline surgical phase recognition is also in significant clinical need for retrospective analysis, and existing online algorithms do not fully analyze the entire video, thereby limiting accuracy in offline analysis. To over-come these challenges and enhance both online and offline inference capabilities, we propose a universal Surgical Phase LocalizAtion Network, named SurgPLAN++, with the principle of temporal detection. To ensure a global understanding of the surgical procedure, we devise a phase localization strategy for SurgPLAN ++ to predict phase segments across the entire video through phase proposals. For online analysis, to generate high-quality phase proposals, SurgPLAN++ incorporates a data augmentation strategy to extend the streaming video into a pseudo-complete video through mirroring, center-duplication, and down-sampling. For offline analysis, SurgPLAN++ capi-talizes on its global phase prediction framework to continu-ously refine preceding predictions during each online inference step, thereby significantly improving the accuracy of phase recognition. We perform extensive experiments to validate the effectiveness, and our SurgPLAN++ achieves remarkable performance in both online and offline modes, which outper-forms state-of-the-art methods. The source code is available at https://github.com/franciszchenlSurgPLAN-Plus.

IROS Conference 2024 Conference Paper

DD-VNB: A Depth-based Dual-Loop Framework for Real-time Visually Navigated Bronchoscopy

  • Qingyao Tian
  • Huai Liao
  • Xinyan Huang
  • Jian Chen 0036
  • Zihui Zhang
  • Bingyu Yang
  • Sébastien Ourselin
  • Hongbin Liu 0001

Real-time 6 DOF localization of bronchoscopes is crucial for enhancing intervention quality. However, current vision-based technologies struggle to balance between generalization to unseen data and computational speed. In this study, we propose a Depth-based Dual-Loop framework for real-time Visually Navigated Bronchoscopy (DD-VNB) that can generalize across patient cases without the need of re-training. The DD-VNB framework integrates two key modules: depth estimation and dual-loop localization. To address the domain gap among patients, we propose a knowledge-embedded depth estimation network that maps endoscope frames to depth, ensuring generalization by eliminating patient-specific textures. The network embeds view synthesis knowledge into a cycle adversarial architecture for scale-constrained monocular depth estimation. For real-time performance, our localization module embeds a fast ego-motion estimation network into the loop of depth registration. The ego-motion inference network estimates the pose change of the bronchoscope in high frequency while depth registration against the pre-operative 3D model provides absolute pose periodically. Specifically, the relative pose changes are fed into the registration process as the initial guess to boost its accuracy and speed. Experiments on phantom and in-vivo data from patients demonstrate the effectiveness of our framework: 1) monocular depth estimation outperforms SOTA, 2) localization achieves an accuracy of Absolute Tracking Error (ATE) of 4. 7 ± 3. 17 mm in phantom and 6. 49 ± 3. 88 mm in patient data, 3) with a frame-rate approaching video capture speed, 4) without the necessity of case-wise network retraining. The framework’s superior speed and accuracy demonstrate its promising clinical potential for real-time bronchoscopic navigation.

YNIMG Journal 2021 Journal Article

Robust parametric modeling of Alzheimer’s disease progression

  • Mostafa Mehdipour Ghazi
  • Mads Nielsen
  • Akshay Pai
  • Marc Modat
  • M. Jorge Cardoso
  • Sébastien Ourselin
  • Lauge Sørensen

Quantitative characterization of disease progression using longitudinal data can provide long-term predictions for the pathological stages of individuals. This work studies the robust modeling of Alzheimer's disease progression using parametric methods. The proposed method linearly maps the individual's age to a disease progression score (DPS) and jointly fits constrained generalized logistic functions to the longitudinal dynamics of biomarkers as functions of the DPS using M-estimation. Robustness of the estimates is quantified using bootstrapping via Monte Carlo resampling, and the estimated inflection points of the fitted functions are used to temporally order the modeled biomarkers in the disease course. Kernel density estimation is applied to the obtained DPSs for clinical status classification using a Bayesian classifier. Different M-estimators and logistic functions, including a novel type proposed in this study, called modified Stannard, are evaluated on the data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) for robust modeling of volumetric magnetic resonance imaging (MRI) and positron emission tomography (PET) biomarkers, cerebrospinal fluid (CSF) measurements, as well as cognitive tests. The results show that the modified Stannard function fitted using the logistic loss achieves the best modeling performance with an average normalized mean absolute error (NMAE) of 0.991 across all biomarkers and bootstraps. Applied to the ADNI test set, this model achieves a multiclass area under the ROC curve (AUC) of 0.934 in clinical status classification. The obtained results for the proposed model outperform almost all state-of-the-art results in predicting biomarker values and classifying clinical status. Finally, the experiments show that the proposed model, trained using abundant ADNI data, generalizes well to data from the National Alzheimer's Coordinating Center (NACC) with an average NMAE of 1.182 and a multiclass AUC of 0.929.

YNIMG Journal 2020 Journal Article

An automated framework for localization, segmentation and super-resolution reconstruction of fetal brain MRI

  • Michael Ebner
  • Guotai Wang
  • Wenqi Li
  • Michael Aertsen
  • Premal A. Patel
  • Rosalind Aughwane
  • Andrew Melbourne
  • Tom Doel

High-resolution volume reconstruction from multiple motion-corrupted stacks of 2D slices plays an increasing role for fetal brain Magnetic Resonance Imaging (MRI) studies. Currently existing reconstruction methods are time-consuming and often require user interactions to localize and extract the brain from several stacks of 2D slices. We propose a fully automatic framework for fetal brain reconstruction that consists of four stages: 1) fetal brain localization based on a coarse segmentation by a Convolutional Neural Network (CNN), 2) fine segmentation by another CNN trained with a multi-scale loss function, 3) novel, single-parameter outlier-robust super-resolution reconstruction, and 4) fast and automatic high-resolution visualization in standard anatomical space suitable for pathological brains. We validated our framework with images from fetuses with normal brains and with variable degrees of ventriculomegaly associated with open spina bifida, a congenital malformation affecting also the brain. Experiments show that each step of our proposed pipeline outperforms state-of-the-art methods in both segmentation and reconstruction comparisons including expert-reader quality assessments. The reconstruction results of our proposed method compare favorably with those obtained by manual, labor-intensive brain segmentation, which unlocks the potential use of automatic fetal brain reconstruction studies in clinical practice.

IROS Conference 2019 Conference Paper

Macro-Micro Multi-Arm Robot for Single-Port Access Surgery

  • T. Vandebroek
  • Mouloud Ourak
  • Caspar Gruijthuijsen
  • Allan Javaux
  • Julie Legrand
  • Tom Vercauteren
  • Sébastien Ourselin
  • Jan Deprest

Minimally invasive surgery is now a well established field in surgery but continuous efforts are made to reduce invasiveness even further. This paper proposes a novel concept of small-diameter multi-arm robot for SinglePort Access Surgery. The concept introduces a combination of backbone and actuation principles in a macro-micro fashion to achieve an excellent decoupling of the triangulation platform (macro) and of the end-effectors (micro). Concentric tube robots are used for the triangulation platform, while compliant fluidic-actuated bending segments are used as end-effectors. The fluidic actuation is advantageous as it minimally interferes with the triangulation platform. The triangulation platform on the other hand provides a stable base for the end-effectors such that large distal actuation bandwidth can be achieved. A specific embodiment for Spina Bifida repair is developed and proposed. The surgical and technical requirements as well as the mechanical design are presented in details. A first prototype is built and characterization experiments are conducted to evaluate its performance.

YNICL Journal 2019 Journal Article

Prion disease diagnosis using subject-specific imaging biomarkers within a multi-kernel Gaussian process

  • Liane S. Canas
  • Carole H. Sudre
  • Enrico De Vita
  • Akin Nihat
  • Tze How Mok
  • Catherine F. Slattery
  • Ross W. Paterson
  • Alexander J.M. Foulkes

Prion diseases are a group of rare neurodegenerative conditions characterised by a high rate of progression and highly heterogeneous phenotypes. Whilst the most common form of prion disease occurs sporadically (sporadic Creutzfeldt-Jakob disease, sCJD), other forms are caused by prion protein gene mutations, or exposure to prions in the diet or by medical procedures, such us surgeries. To date, there are no accurate quantitative imaging biomarkers that can be used to predict the future clinical diagnosis of a healthy subject, or to quantify the progression of symptoms over time. Besides, CJD is commonly mistaken for other forms of dementia. Due to the heterogeneity of phenotypes and the lack of a consistent geometrical pattern of disease progression, the approaches used to study other types of neurodegenerative diseases are not satisfactory to capture the progression of human form of prion disease. In this paper, using a tailored framework, we aim to classify and stratify patients with prion disease, according to the severity of their illness. The framework is initialised with the extraction of subject-specific imaging biomarkers. The extracted biomakers are then combined with genetic and demographic information within a Gaussian Process classifier, used to calculate the probability of a subject to be diagnosed with prion disease in the next year. We evaluate the effectiveness of the proposed method in a cohort of patients with inherited and sporadic forms of prion disease. The model has shown to be effective in the prediction of both inherited CJD (92% of accuracy) and sporadic CJD (95% of accuracy). However the model has shown to be less effective when used to stratify the different stages of the disease, in which the average accuracy is 85%, whilst the recall is 59%. Finally, our framework was extended as a differential diagnosis tool to identify both forms of CJD among another neurodegenerative disease. In summary we have developed a novel method for prion disease diagnosis and prediction of clinical onset using multiple sources of features, which may have use in other disorders with heterogeneous imaging features.

ICRA Conference 2019 Conference Paper

Robotic Control of a Multi-Modal Rigid Endoscope Combining Optical Imaging with All-Optical Ultrasound

  • George Dwyer
  • Richard J. Colchester
  • Erwin J. Alles
  • Efthymios Maneas
  • Sébastien Ourselin
  • Tom Vercauteren
  • Jan Deprest
  • Emmanuel B. Vander Poorten

Fetoscopy is a technically challenging surgery, due to the dynamic environment and low diameter endoscopes often resulting in a limited field of view. In this paper, we report on the design and operation of a robotic multimodal endoscope with optical ultrasound and white light stereo camera. The manufacture and control of the endoscope is presented, along with large area (80 mm ×80 mm) surface visualisations of a placenta phantom using the optical ultrasound sensor. The repeatability of the surface visualisations was found to be 0. 446 ± 0. 139 mm and 0. 267 ± 0. 017 mm for a raster and spiral scan, respectively.

ICRA Conference 2018 Conference Paper

Requirements Based Design and End-to-End Dynamic Modeling of a Robotic Tool for Vitreoretinal Surgery

  • Anestis Mablekos-Alexiou
  • Sébastien Ourselin
  • Lyndon Da Cruz
  • Christos Bergeles

Despite several robots having been proposed for vitreoretinal surgery, there is limited information on their dynamic modeling. This gap leads to sub-optimal motor selection and hinders the application of advanced control schemes that would fulfill the goal of micro-precise surgery. This paper presents the design process and a dynamics study of a multi-Degree of Freedom (DoF) robotic system, which is inspired by established co-manipulation architectures. A rigorous kinematics and dynamics analysis of the robot's part that is responsible for manipulating the surgical tool during the retinal surgery phase is provided. In particular, the Euler-Lagrange equations of motion, which describe the dynamics of the 3-link surgical manipulator, are combined with novel analytical models of each link's corresponding transmission mechanism, including an anti-backlash lead screw assembly and a worm drive. The resulting models, transferable to existing manipulators, provide a meticulous analysis of the robot's performance that can be used both for mechanical design and control purposes.

YNIMG Journal 2018 Journal Article

Volumetric reconstruction from printed films: Enabling 30 year longitudinal analysis in MR neuroimaging

  • Michael Ebner
  • Karen K. Chung
  • Ferran Prados
  • M. Jorge Cardoso
  • Declan T. Chard
  • Tom Vercauteren
  • Sébastien Ourselin

Hospitals often hold historical MR image data printed on films without being able to make it accessible to modern image processing techniques. Having the possibility to recover geometrically consistent, volumetric images from scans acquired decades ago will enable more comprehensive, longitudinal studies to understand disease progressions. In this paper, we propose a consistent framework to reconstruct a volumetric representation from printed films holding thick single-slice brain MR image acquisitions dating back to the 1980's. We introduce a flexible framework based on semi-automatic slice extraction, followed by automated slice-to-volume registration with inter-slice transformation regularisation and slice intensity correction. Our algorithm is robust against numerous detrimental effects being present in archaic films. A subsequent, isotropic total variation deconvolution technique revitalises the visual appearance of the obtained volumes. We assess the accuracy and perform the validation of our reconstruction framework on a uniquely long-term MRI dataset where a ground-truth is available. This method will be used to facilitate a robust longitudinal analysis spanning 30 years of MRI scans.

IROS Conference 2017 Conference Paper

Body wall force sensor for simulated minimally invasive surgery: Application to fetal surgery

  • Allan Javaux
  • Laure Esteveny
  • David Bouget
  • Caspar Gruijthuijsen
  • Danail Stoyanov
  • Tom Vercauteren
  • Sébastien Ourselin
  • Dominiek Reynaerts

Surgical interventions are increasingly executed minimal invasively. Surgeons insert instruments through tiny incisions in the body and pivot slender instruments to treat organs or tissue below the surface. While a blessing for patients, surgeons need to pay extra attention to overcome the fulcrum effect, reduced haptic feedback and deal with lost hand-eye coordination. The mental load makes it difficult to pay sufficient attention to the forces that are exerted on the body wall. In delicate procedures such as fetal surgery, this might be problematic as irreparable damage could cause premature delivery. As a first attempt to quantify the interaction forces applied on the patient's body wall, a novel 6 degrees of freedom force sensor was developed for an ex-vivo set up. The performance of the sensor was characterised. User experiments were conducted by 3 clinicians on a set up simulating a fetal surgical intervention. During these simulated interventions, the interaction forces were recorded and analysed when a normal instrument was employed. These results were compared with a session where a flexible instrument under haptic guidance was used. The conducted experiments resulted in interesting insights in the interaction forces and stresses that develop during such difficult surgical intervention. The results also implicated that haptic guidance schemes and the use of flexible instruments rather than rigid ones could have a significant impact on the stresses that occur at the body wall.

YNIMG Journal 2017 Journal Article

Longitudinal multiple sclerosis lesion segmentation: Resource and challenge

  • Aaron Carass
  • Snehashis Roy
  • Amod Jog
  • Jennifer L. Cuzzocreo
  • Elizabeth Magrath
  • Adrian Gherman
  • Julia Button
  • James Nguyen

In conjunction with the ISBI 2015 conference, we organized a longitudinal lesion segmentation challenge providing training and test data to registered participants. The training data consisted of five subjects with a mean of 4. 4 time-points, and test data of fourteen subjects with a mean of 4. 4 time-points. All 82 data sets had the white matter lesions associated with multiple sclerosis delineated by two human expert raters. Eleven teams submitted results using state-of-the-art lesion segmentation algorithms to the challenge, with ten teams presenting their results at the conference. We present a quantitative evaluation comparing the consistency of the two raters as well as exploring the performance of the eleven submitted results in addition to three other lesion segmentation algorithms. The challenge presented three unique opportunities: (1) the sharing of a rich data set; (2) collaboration and comparison of the various avenues of research being pursued in the community; and (3) a review and refinement of the evaluation metrics currently in use. We report on the performance of the challenge participants, as well as the construction and evaluation of a consensus delineation. The image data and manual delineations will continue to be available for download, through an evaluation website 2 2 The Challenge Evaluation Website is: http: //smart-stats-tools. org/lesion-challenge-2015 as a resource for future researchers in the area. This data resource provides a platform to compare existing methods in a fair and consistent manner to each other and multiple manual raters.

YNICL Journal 2017 Journal Article

Selection bias in the reported performances of AD classification pipelines

  • Alex F. Mendelson
  • Maria A. Zuluaga
  • Marco Lorenzi
  • Brian F. Hutton
  • Sébastien Ourselin

The last decade has seen a great proliferation of supervised learning pipelines for individual diagnosis and prognosis in Alzheimer's disease. As more pipelines are developed and evaluated in the search for greater performance, only those results that are relatively impressive will be selected for publication. We present an empirical study to evaluate the potential for optimistic bias in classification performance results as a result of this selection. This is achieved using a novel, resampling-based experiment design that effectively simulates the optimisation of pipeline specifications by individuals or collectives of researchers using cross validation with limited data. Our findings indicate that bias can plausibly account for an appreciable fraction (often greater than half) of the apparent performance improvement associated with the pipeline optimisation, particularly in small samples. We discuss the consistency of our findings with patterns observed in the literature and consider strategies for bias reduction and mitigation.

IROS Conference 2017 Conference Paper

ToolNet: Holistically-nested real-time segmentation of robotic surgical tools

  • Luis C. García-Peraza-Herrera
  • Wenqi Li 0001
  • Lucas Fidon
  • Caspar Gruijthuijsen
  • Alain Devreker
  • George Attilakos
  • Jan Deprest
  • Emmanuel B. Vander Poorten

Real-time tool segmentation from endoscopic videos is an essential part of many computer-assisted robotic surgical systems and of critical importance in robotic surgical data science. We propose two novel deep learning architectures for automatic segmentation of non-rigid surgical instruments. Both methods take advantage of automated deep-learning-based multi-scale feature extraction while trying to maintain an accurate segmentation quality at all resolutions. The two proposed methods encode the multi-scale constraint inside the network architecture. The first proposed architecture enforces it by cascaded aggregation of predictions and the second proposed network does it by means of a holistically-nested architecture where the loss at each scale is taken into account for the optimization process. As the proposed methods are for real-time semantic labeling, both present a reduced number of parameters. We propose the use of parametric rectified linear units for semantic labeling in these small architectures to increase the regularization of the network while maintaining the segmentation accuracy. We compare the proposed architectures against state-of-the-art fully convolutional networks. We validate our methods using existing benchmark datasets, including ex vivo cases with phantom tissue and different robotic surgical instruments present in the scene. Our results show a statistically significant improved Dice Similarity Coefficient over previous instrument segmentation methods. We analyze our design choices and discuss the key drivers for improving accuracy.

YNICL Journal 2017 Journal Article

White matter hyperintensities are seen only in GRN mutation carriers in the GENFI cohort

  • Carole H. Sudre
  • Martina Bocchetta
  • David Cash
  • David L. Thomas
  • Ione Woollacott
  • Katrina M. Dick
  • John van Swieten
  • Barbara Borroni

Genetic frontotemporal dementia is most commonly caused by mutations in the progranulin (GRN), microtubule-associated protein tau (MAPT) and chromosome 9 open reading frame 72 (C9orf72) genes. Previous small studies have reported the presence of cerebral white matter hyperintensities (WMH) in genetic FTD but this has not been systematically studied across the different mutations. In this study WMH were assessed in 180 participants from the Genetic FTD Initiative (GENFI) with 3D T1- and T2-weighed magnetic resonance images: 43 symptomatic (7 GRN, 13 MAPT and 23 C9orf72), 61 presymptomatic mutation carriers (25 GRN, 8 MAPT and 28 C9orf72) and 76 mutation negative non-carrier family members. An automatic detection and quantification algorithm was developed for determining load, location and appearance of WMH. Significant differences were seen only in the symptomatic GRN group compared with the other groups with no differences in the MAPT or C9orf72 groups: increased global load of WMH was seen, with WMH located in the frontal and occipital lobes more so than the parietal lobes, and nearer to the ventricles rather than juxtacortical. Although no differences were seen in the presymptomatic group as a whole, in the GRN cohort only there was an association of increased WMH volume with expected years from symptom onset. The appearance of the WMH was also different in the GRN group compared with the other groups, with the lesions in the GRN group being more similar to each other. The presence of WMH in those with progranulin deficiency may be related to the known role of progranulin in neuroinflammation, although other roles are also proposed including an effect on blood-brain barrier permeability and the cerebral vasculature. Future studies will be useful to investigate the longitudinal evolution of WMH and their potential use as a biomarker as well as post-mortem studies investigating the histopathological nature of the lesions.

IROS Conference 2015 Conference Paper

Fluidic actuation for intra-operative in situ imaging

  • Alain Devreker
  • Benoit Rosa
  • Adrien E. Desjardins
  • Erwin J. Alles
  • Luis C. García-Peraza-Herrera
  • Efthymios Maneas
  • Danail Stoyanov
  • Anna L. David

A novel fluidic actuation system has been developed for in situ imaging of anatomic tissues. The actuator consists of a micromachined superelastic tool guide driven by a pair of pneumatic artificial muscles. Two additional working channels allow easy interchange of instruments or sensing equipment. This paper describes the design and construction of the actuation system. Experimental results are also reported indicating a bending repeatability of 0. 1 degrees and an operational bandwidth exceeding 8Hz. To show-case the performance of the device, the actuator was loaded with an all-optical ultrasound imaging probe. First scanned images of human placental tissue surface using an all-optical ultrasound probe are presented. While a model has been developed to estimate the probe position in space as function of the input pressure, in future work, this model will be complemented with additional sensor measurements of the bending probe taking into account the hysteretic behaviour of both muscles and nitinol structure.

YNIMG Journal 2012 Journal Article

Consistent multi-time-point brain atrophy estimation from the boundary shift integral

  • Kelvin K. Leung
  • Gerard R. Ridgway
  • Sébastien Ourselin
  • Nick C. Fox

Brain atrophy measurement is increasingly important in studies of neurodegenerative diseases such as Alzheimer's disease (AD), with particular relevance to trials of potential disease-modifying drugs. Automated registration-based methods such as the boundary shift integral (BSI) have been developed to provide more precise measures of change from a pair of serial MR scans. However, when a method treats one image of the pair (typically the baseline) as the reference to which the other is compared, this systematic asymmetry risks introducing bias into the measurement. Recent concern about potential biases in longitudinal studies has led to several suggestions to use symmetric image registration, though some of these methods are limited to two time-points per subject. Therapeutic trials and natural history studies increasingly involve several serial scans, it would therefore be useful to have a method that can consistently estimate brain atrophy over multiple time-points. Here, we use the log-Euclidean concept of a within-subject average to develop affine registration and differential bias correction methods suitable for any number of time-points, yielding a longitudinally consistent multi-time-point BSI technique. Baseline, 12-month and 24-month MR scans of healthy controls, subjects with mild cognitive impairment and AD patients from the Alzheimer's Disease Neuroimaging Initiative are used for testing the bias in processing scans with different amounts of atrophy. Four tests are used to assess bias in brain volume loss from BSI: (a) inverse consistency with respect to ordering of pairs of scans 12months apart; (b) transitivity consistency over three time-points; (c) randomly ordered back-to-back scans, expected to show no consistent change over subjects; and (d) linear regression of the atrophy rates calculated from the baseline and 12-month scans and the baseline and 24-month scans, where any additive bias should be indicated by a non-zero intercept. Results indicate that the traditional BSI processing pipeline does not exhibit significant bias due to its use of windowed sinc interpolation, but with linear interpolation and asymmetric registration, bias can be pronounced. Either improved interpolation or symmetric registration alone can greatly reduce this bias, and our proposed method combining both aspects shows no significant bias in any of the four experiments.

YNIMG Journal 2011 Journal Article

A comparison of voxel and surface based cortical thickness estimation methods

  • Matthew J. Clarkson
  • M. Jorge Cardoso
  • Gerard R. Ridgway
  • Marc Modat
  • Kelvin K. Leung
  • Jonathan D. Rohrer
  • Nick C. Fox
  • Sébastien Ourselin

Cortical thickness estimation performed in-vivo via magnetic resonance imaging is an important technique for the diagnosis and understanding of the progression of neurodegenerative diseases. Currently, two different computational paradigms exist, with methods generally classified as either surface or voxel-based. This paper provides a much needed comparison of the surface-based method FreeSurfer and two voxel-based methods using clinical data. We test the effects of computing regional statistics using two different atlases and demonstrate that this makes a significant difference to the cortical thickness results. We assess reproducibility, and show that FreeSurfer has a regional standard deviation of thickness difference on same day scans that is significantly lower than either a Laplacian or Registration based method and discuss the trade off between reproducibility and segmentation accuracy caused by bending energy constraints. We demonstrate that voxel-based methods can detect similar patterns of group-wise differences as well as FreeSurfer in typical applications such as producing group-wise maps of statistically significant thickness change, but that regional statistics can vary between methods. We use a Support Vector Machine to classify patients against controls and did not find statistically significantly different results with voxel based methods compared to FreeSurfer. Finally we assessed longitudinal performance and concluded that currently FreeSurfer provides the most plausible measure of change over time, with further work required for voxel based methods.

YNIMG Journal 2011 Journal Article

Brain MAPS: An automated, accurate and robust brain extraction technique using a template library

  • Kelvin K. Leung
  • Josephine Barnes
  • Marc Modat
  • Gerard R. Ridgway
  • Jonathan W. Bartlett
  • Nick C. Fox
  • Sébastien Ourselin

Whole brain extraction is an important pre-processing step in neuroimage analysis. Manual or semi-automated brain delineations are labour-intensive and thus not desirable in large studies, meaning that automated techniques are preferable. The accuracy and robustness of automated methods are crucial because human expertise may be required to correct any suboptimal results, which can be very time consuming. We compared the accuracy of four automated brain extraction methods: Brain Extraction Tool (BET), Brain Surface Extractor (BSE), Hybrid Watershed Algorithm (HWA) and a Multi-Atlas Propagation and Segmentation (MAPS) technique we have previously developed for hippocampal segmentation. The four methods were applied to extract whole brains from 682 1. 5T and 157 3T T1-weighted MR baseline images from the Alzheimer's Disease Neuroimaging Initiative database. Semi-automated brain segmentations with manual editing and checking were used as the gold-standard to compare with the results. The median Jaccard index of MAPS was higher than HWA, BET and BSE in 1. 5T and 3T scans (p <0. 05, all tests), and the 1st to 99th centile range of the Jaccard index of MAPS was smaller than HWA, BET and BSE in 1. 5T and 3T scans ( p <0. 05, all tests). HWA and MAPS were found to be best at including all brain tissues (median false negative rate ≤0. 010% for 1. 5T scans and ≤0. 019% for 3T scans, both methods). The median Jaccard index of MAPS were similar in both 1. 5T and 3T scans, whereas those of BET, BSE and HWA were higher in 1. 5T scans than 3T scans (p <0. 05, all tests). We found that the diagnostic group had a small effect on the median Jaccard index of all four methods. In conclusion, MAPS had relatively high accuracy and low variability compared to HWA, BET and BSE in MR scans with and without atrophy.

YNIMG Journal 2010 Journal Article

Robust atrophy rate measurement in Alzheimer's disease using multi-site serial MRI: Tissue-specific intensity normalization and parameter selection

  • Kelvin K. Leung
  • Matthew J. Clarkson
  • Jonathan W. Bartlett
  • Shona Clegg
  • Clifford R. Jack
  • Michael W. Weiner
  • Nick C. Fox
  • Sébastien Ourselin

We describe an improved method of measuring brain atrophy rates from serial MRI for multi-site imaging studies of Alzheimer's disease (AD). The method (referred to as KN-BSI) improves an existing brain atrophy measurement technique—the boundary shift integral (classic-BSI), by performing tissue-specific intensity normalization and parameter selection. We applied KN-BSI to measure brain atrophy rates of 200 normal and 141 AD subjects using baseline and 1-year MRI scans downloaded from the Alzheimer's Disease Neuroimaging Initiative database. Baseline and repeat images were reviewed as pairs by expert raters and given quality scores. Including all image pairs, regardless of quality score, mean KN-BSI atrophy rates were 0. 09% higher (95% CI 0. 03% to 0. 16%, p =0. 007) than classic-BSI rates in controls and 0. 07% higher (−0. 01% to 0. 16%, p =0. 07) higher in ADs. The SD of the KN-BSI rates was 22% lower (15% to 29%, p <0. 001) in controls and 13% lower (6% to 20%, p =0. 001) in ADs, compared to classic-BSI. Using these results, the estimated sample size (needed per treatment arm) for a hypothetical trial of a treatment for AD (80% power, 5% significance to detect a 25% reduction in atrophy rate) would be reduced from 120 to 81 (a 32% reduction, 95% CI=18% to 45%, p <0. 001) when using KN-BSI instead of classic-BSI. We concluded that KN-BSI offers more robust brain atrophy measurement than classic-BSI and substantially reduces sample sizes needed in clinical trials.

YNIMG Journal 2009 Journal Article

Comparison of phantom and registration scaling corrections using the ADNI cohort

  • Matthew J. Clarkson
  • Sébastien Ourselin
  • Casper Nielsen
  • Kelvin K. Leung
  • Josephine Barnes
  • Jennifer L. Whitwell
  • Jeffrey L. Gunter
  • Derek L.G. Hill

Rates of brain atrophy derived from serial magnetic resonance (MR) studies may be used to assess therapies for Alzheimer's disease (AD). These measures may be confounded by changes in scanner voxel sizes. For this reason, the Alzheimer's Disease Neuroimaging Initiative (ADNI) included the imaging of a geometric phantom with every scan. This study compares voxel scaling correction using a phantom with correction using a 9 degrees of freedom (9DOF) registration algorithm. We took 129 pairs of baseline and 1-year repeat scans, and calculated the volume scaling correction, previously measured using the phantom. We used the registration algorithm to quantify any residual scaling errors, and found the algorithm to be unbiased, with no significant (p =0. 97) difference between control (n =79) and AD subjects (n =50), but with a mean (SD) absolute volume change of 0. 20 (0. 20) % due to linear scalings. 9DOF registration was shown to be comparable to geometric phantom correction in terms of the effect on atrophy measurement and unbiased with respect to disease status. These results suggest that the additional expense and logistic effort of scanning a phantom with every patient scan can be avoided by registration-based scaling correction. Furthermore, based upon the atrophy rates in the AD subjects in this study, sample size requirements would be approximately 10–12% lower with (either) correction for voxel scaling than if no correction was used.

YNIMG Journal 2008 Journal Article

Appearance modeling of 11C PiB PET images: Characterizing amyloid deposition in Alzheimer's disease, mild cognitive impairment and healthy aging

  • Jurgen Fripp
  • Pierrick Bourgeat
  • Oscar Acosta
  • Parnesh Raniga
  • Marc Modat
  • Kerryn E Pike
  • Gareth Jones
  • Graeme O'Keefe

β-amyloid (Aβ) deposition is one of the neuropathological hallmarks of Alzheimer's disease (AD), Aβ burden can be quantified using 11C PiB PET. Neuropathological studies have shown that the initial plaques are located in the temporal and orbitofrontal cortices, extending later to the cingulate, frontal and parietal cortices (Braak and Braak, 1997). Previous studies have shown an overlap in 11C PiB PET retention between AD, mild cognitive impairment (MCI) patients and normal elderly control (NC) participants. It has also been shown that there is a relationship between Aβ deposition and memory impairment in MCI patients. In this paper we explored the variability seen in 15 AD, 15 MCI and 18 NC by modeling the voxel data from spatially and uptake normalized PiB images using principal component analysis. The first two principal components accounted for 80% of the variability seen in the data, providing a clear separation between AD and NC, and allowing subsequent classification. The MCI cases were distributed along an apparent axis between the AD and NC group, closely aligned with the first principal component axis. The NC cases that were PiB + formed a distinct cluster that was between, but separated from the AD and PiB − NC clusters. The PiB + MCI were found to cluster with the AD cases, and exhibited a similar deposition pattern. The primary principal component score was found to correlate with episodic memory scores and mini mental status examination and it was observed that by varying the first principal component, a change in amyloid deposition could be derived that is similar to the expected progression of amyloid deposition observed from post mortem studies.

YNIMG Journal 2007 Journal Article

A three-dimensional, histological and deformable atlas of the human basal ganglia. I. Atlas construction based on immunohistochemical and MRI data

  • Jérôme Yelnik
  • Eric Bardinet
  • Didier Dormont
  • Grégoire Malandain
  • Sébastien Ourselin
  • Dominique Tandé
  • Carine Karachi
  • Nicholas Ayache

This paper describes the construction of an atlas of the human basal ganglia. The successive steps of the construction were as follows. First a postmortem specimen was subjected to a MRI acquisition prior to extraction of the brain from the skull. The brain was then cryosectioned (70 μm thickness). One section out of ten (80 sections) was Nissl-stained with cresyl violet, another series of 80 sections was immunostained for the calcium binding protein calbindin. Contours of basal ganglia nuclei including their calbindin-stained functional subdivisions, fiber bundles and ventricles (n =80 structures) were traced from histological sections and digitized. A novelty of this atlas is the MRI acquisition, which represents the core data element of the study. MRI was used for the coregistration of the atlas data and permitted, through multimodal (Nissl, calbindin, images of cryosectioning, T1 and T2 MRI) and 3D optimization, the production of anatomically and geometrically consistent 3D surfaces, which can be sliced through any desired orientation. The atlas MRI is also used for its deformation to provide accurate conformation to the MRI of living patients, thus adding information at the histological level to the patient's MRI volume. This latter aspect will be presented in a forthcoming paper.

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