Publications by authors named "Toby Collins"

36 Publications

Definitions of Computer-Assisted Surgery and Intervention, Image-Guided Surgery and Intervention, Hybrid Operating Room, and Guidance Systems: Strasbourg International Consensus Study.

Ann Surg Open 2020 Dec 20;1(2):e021. Epub 2020 Nov 20.

Research Institute against Cancer of the Digestive System (IRCAD), Strasbourg, France.

Objective: To develop consensus definitions of image-guided surgery, computer-assisted surgery, hybrid operating room, and surgical navigation systems.

Summary Background Data: The use of minimally invasive procedures has increased tremendously over the past 2 decades, but terminology related to image-guided minimally invasive procedures has not been standardized, which is a barrier to clear communication.

Methods: Experts in image-guided techniques and specialized engineers were invited to engage in a systematic process to develop consensus definitions of the key terms listed above. The process was designed following review of common consensus-development methodologies and included participation in 4 online surveys and a post-surveys face-to-face panel meeting held in Strasbourg, France.

Results: The experts settled on the terms computer-assisted surgery and intervention, image-guided surgery and intervention, hybrid operating room, and guidance systems and agreed-upon definitions of these terms, with rates of consensus of more than 80% for each term. The methodology used proved to be a compelling strategy to overcome the current difficulties related to data growth rates and technological convergence in this field.

Conclusions: Our multidisciplinary collaborative approach resulted in consensus definitions that may improve communication, knowledge transfer, collaboration, and research in the rapidly changing field of image-guided minimally invasive techniques.
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http://dx.doi.org/10.1097/AS9.0000000000000021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7771637PMC
December 2020

Hyperspectral evaluation of hepatic oxygenation in a model of total vs. arterial liver ischaemia.

Sci Rep 2020 09 22;10(1):15441. Epub 2020 Sep 22.

Institute of Physiology, EA3072 Mitochondria Respiration and Oxidative Stress, University of Strasbourg, Strasbourg, France.

Liver ischaemia reperfusion injury (IRI) is a dreaded pathophysiological complication which may lead to an impaired liver function. The level of oxygen hypoperfusion affects the level of cellular damage during the reperfusion phase. Consequently, intraoperative localisation and quantification of oxygen impairment would help in the early detection of liver ischaemia. To date, there is no real-time, non-invasive, and intraoperative tool which can compute an organ oxygenation map, quantify and discriminate different types of vascular occlusions intraoperatively. Hyperspectral imaging (HSI) is a non-invasive optical methodology which can quantify tissue oxygenation and which has recently been applied to the medical field. A hyperspectral camera detects the relative reflectance of a tissue in the range of 500 to 1000 nm, allowing the quantification of organic compounds such as oxygenated and deoxygenated haemoglobin at different depths. Here, we show the first comparative study of liver oxygenation by means of HSI quantification in a model of total vascular inflow occlusion (VIO) vs. hepatic artery occlusion (HAO), correlating optical properties with capillary lactate and histopathological evaluation. We found that liver HSI could discriminate between VIO and HAO. These results were confirmed via cross-validation of HSI which detected and quantified intestinal congestion in VIO. A significant correlation between the near-infrared spectra and capillary lactate was found (r = - 0.8645, p = 0.0003 VIO, r = - 0.7113, p = 0.0120 HAO). Finally, a statistically significant negative correlation was found between the histology score and the near-infrared parameter index (NIR) (r = - 0.88, p = 0.004). We infer that HSI, by predicting capillary lactates and the histopathological score, would be a suitable non-invasive tool for intraoperative liver perfusion assessment.
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http://dx.doi.org/10.1038/s41598-020-72915-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7509803PMC
September 2020

Bridging the Gap Between RCTs and RWE Through Endpoint Selection.

Ther Innov Regul Sci 2021 Jan 6;55(1):90-96. Epub 2020 Jul 6.

Real-World Evidence Center of Excellence, AstraZeneca, Cambridge, UK.

This commentary is authored by several industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of Industry Leaders who have come together as non-competitive partners to understand and respond to RWD/E challenges and opportunities with a single expert voice. Here, the forum discusses the value in bridging the industry disconnect between RTCs and RWE, with a view to promoting the use of RWE in the RCT environment. RCT endpoints are explored along several axes including their clinical relevance and their measure of direct patient benefit, and then compared with their real-world counterparts to identify suitable paths, or gaps, for assimilating RWE endpoints into the RCT environment.
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http://dx.doi.org/10.1007/s43441-020-00193-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785541PMC
January 2021

Automatic task recognition in a flexible endoscopy benchtop trainer with semi-supervised learning.

Int J Comput Assist Radiol Surg 2020 Sep 26;15(9):1585-1595. Epub 2020 Jun 26.

IRCAD Strasbourg, Strasbourg, France.

Purpose: Inexpensive benchtop training systems offer significant advantages to meet the increasing demand of training surgeons and gastroenterologists in flexible endoscopy. Established scoring systems exist, based on task duration and mistake evaluation. However, they require trained human raters, which limits broad and low-cost adoption. There is an unmet and important need to automate rating with machine learning.

Method: We present a general and robust approach for recognizing training tasks from endoscopic training video, which consequently automates task duration computation. Our main technical novelty is to show the performance of state-of-the-art CNN-based approaches can be improved significantly with a novel semi-supervised learning approach, using both labelled and unlabelled videos. In the latter case, we assume only the task execution order is known a priori.

Results: Two video datasets are presented: the first has 19 videos recorded in examination conditions, where the participants complete their tasks in predetermined order. The second has 17 h of videos recorded in self-assessment conditions, where participants complete one or more tasks in any order. For the first dataset, we obtain a mean task duration estimation error of 3.65 s, with a mean task duration of 159 s ([Formula: see text] relative error). For the second dataset, we obtain a mean task duration estimation error of 3.67 s. We reduce an average of 5.63% in error to 3.67% thanks to our semi-supervised learning approach.

Conclusion: This work is the first significant step forward to automate rating of flexible endoscopy students using a low-cost benchtop trainer. Thanks to our semi-supervised learning approach, we can scale easily to much larger unlabelled training datasets. The approach can also be used for other phase recognition tasks.
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http://dx.doi.org/10.1007/s11548-020-02208-wDOI Listing
September 2020

Light modelling and calibration in laparoscopy.

Int J Comput Assist Radiol Surg 2020 May 28;15(5):859-866. Epub 2020 Apr 28.

EnCoV, Institut Pascal, UMR 6602, CNRS/UBP/SIGMA, EnCoV, 63000, Clermont-Ferrand, France.

Purpose: A better understanding of photometry in laparoscopic images can increase the reliability of computer-assisted surgery applications. Photometry requires modelling illumination, tissue reflectance and camera response. There exists a large variety of light models, but no systematic and reproducible evaluation. We present a review of light models in laparoscopic surgery, a unified calibration approach, an evaluation methodology, and a practical use of photometry.

Method: We use images of a calibration checkerboard to calibrate the light models. We then use these models in a proposed dense stereo algorithm exploiting the shading and simultaneously extracting the tissue albedo, which we call dense shading stereo. The approach works with a broad range of light models, giving us a way to test their respective merits.

Results: We show that overly complex light models are usually not needed and that the light source position must be calibrated. We also show that dense shading stereo outperforms existing methods, in terms of both geometric and photometric errors, and achieves sub-millimeter accuracy.

Conclusion: This work demonstrates the importance of careful light modelling and calibration for computer-assisted surgical applications. It gives guidelines on choosing the best performing light model.
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http://dx.doi.org/10.1007/s11548-020-02161-8DOI Listing
May 2020

Erratum.

Surg Oncol Clin N Am 2020 Apr;29(2):xi

IHU-Strasbourg, Institute of Image-Guided Surgery, 1 Place de l'Hôpital, Strasbourg 67091, France; IRCAD, Research Institute Against Cancer of the Digestive System, 1 Place de l'Hôpital, Strasbourg 67091, France; Department of General, Digestive and Endocrine Surgery, University Hospital of Strasbourg, 1 Place de l'Hôpital, Strasbourg 67091, France. Electronic address:

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http://dx.doi.org/10.1016/j.soc.2020.02.011DOI Listing
April 2020

An in vivo porcine dataset and evaluation methodology to measure soft-body laparoscopic liver registration accuracy with an extended algorithm that handles collisions.

Int J Comput Assist Radiol Surg 2019 Jul 30;14(7):1237-1245. Epub 2019 May 30.

IRCAD and IHU-Strasbourg, 1 Place de l'Hopital, 67000, Strasbourg, France.

Purpose: The registration of preoperative 3D images to intra-operative laparoscopic 2D images is one of the main concerns for augmented reality in computer-assisted surgery. For laparoscopic liver surgery, while several algorithms have been proposed, there is neither a public dataset nor a systematic evaluation methodology to quantitatively evaluate registration accuracy.

Method: Our main contribution is to provide such a dataset with an in vivo porcine model. It is used to evaluate a state-of-the-art registration algorithm that is capable of simultaneous registration and soft-body collision reasoning.

Results: The dataset consists of 13 deformed liver states, with corresponding exploration videos and interventional CT acquisitions with 60 small artificial fiducials located on the surface of the liver and distributed within the parenchyma, where a precise registration is crucial for augmented reality. This dataset will be made public. Using this dataset, we show that collision reasoning improves performance of registration for strong deformation and independent lobe motion.

Conclusion: This dataset addresses the lack of public datasets in this field. As an example of use, we present and evaluate a state-of-the-art energy-based approach and a novel extension that handles self-collisions.
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http://dx.doi.org/10.1007/s11548-019-02001-4DOI Listing
July 2019

Virtual and Augmented Reality in Oncologic Liver Surgery.

Surg Oncol Clin N Am 2019 01 23;28(1):31-44. Epub 2018 Oct 23.

IHU-Strasbourg, Institute of Image-Guided Surgery, 1 Place de l'Hôpital, Strasbourg 67091, France; IRCAD, Research Institute Against Cancer of the Digestive System, 1 Place de l'Hôpital, Strasbourg 67091, France; Department of General, Digestive and Endocrine Surgery, University Hospital of Strasbourg, 1 Place de l'Hôpital, Strasbourg 67091, France. Electronic address:

Virtual reality (VR) and augmented reality (AR) in complex surgery are evolving technologies enabling improved preoperative planning and intraoperative navigation. The basis of these technologies is a computer-based generation of a patient-specific 3-dimensional model from Digital Imaging and Communications in Medicine (DICOM) data. This article provides a state-of-the- art overview on the clinical use of this technology with a specific focus on hepatic surgery. Although VR and AR are still in an evolving stage with only some clinical application today, these technologies have the potential to become a key factor in improving preoperative and intraoperative decision making.
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http://dx.doi.org/10.1016/j.soc.2018.08.002DOI Listing
January 2019

Live Tracking and Dense Reconstruction for Handheld Monocular Endoscopy.

IEEE Trans Med Imaging 2019 01 13;38(1):79-89. Epub 2018 Jul 13.

Contemporary endoscopic simultaneous localization and mapping (SLAM) methods accurately compute endoscope poses; however, they only provide a sparse 3-D reconstruction that poorly describes the surgical scene. We propose a novel dense SLAM method whose qualities are: 1) monocular, requiring only RGB images of a handheld monocular endoscope; 2) fast, providing endoscope positional tracking and 3-D scene reconstruction, running in parallel threads; 3) dense, yielding an accurate dense reconstruction; 4) robust, to the severe illumination changes, poor texture and small deformations that are typical in endoscopy; and 5) self-contained, without needing any fiducials nor external tracking devices and, therefore, it can be smoothly integrated into the surgical workflow. It works as follows. First, accurate cluster frame poses are estimated using the sparse SLAM feature matches. The system segments clusters of video frames according to parallax criteria. Next, dense matches between cluster frames are computed in parallel by a variational approach that combines zero mean normalized cross correlation and a gradient Huber norm regularizer. This combination copes with challenging lighting and textures at an affordable time budget on a modern GPU. It can outperform pure stereo reconstructions, because the frames cluster can provide larger parallax from the endoscope's motion. We provide an extensive experimental validation on real sequences of the porcine abdominal cavity, both in-vivo and ex-vivo. We also show a qualitative evaluation on human liver. In addition, we show a comparison with the other dense SLAM methods showing the performance gain in terms of accuracy, density, and computation time.
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http://dx.doi.org/10.1109/TMI.2018.2856109DOI Listing
January 2019

Trisomy of human chromosome 21 enhances amyloid-β deposition independently of an extra copy of APP.

Brain 2018 08;141(8):2457-2474

Department of Neurodegenerative Disease, UCL Institute of Neurology, London, WC1N 3BG UK.

Down syndrome, caused by trisomy of chromosome 21, is the single most common risk factor for early-onset Alzheimer's disease. Worldwide approximately 6 million people have Down syndrome, and all these individuals will develop the hallmark amyloid plaques and neurofibrillary tangles of Alzheimer's disease by the age of 40 and the vast majority will go on to develop dementia. Triplication of APP, a gene on chromosome 21, is sufficient to cause early-onset Alzheimer's disease in the absence of Down syndrome. However, whether triplication of other chromosome 21 genes influences disease pathogenesis in the context of Down syndrome is unclear. Here we show, in a mouse model, that triplication of chromosome 21 genes other than APP increases amyloid-β aggregation, deposition of amyloid-β plaques and worsens associated cognitive deficits. This indicates that triplication of chromosome 21 genes other than APP is likely to have an important role to play in Alzheimer's disease pathogenesis in individuals who have Down syndrome. We go on to show that the effect of trisomy of chromosome 21 on amyloid-β aggregation correlates with an unexpected shift in soluble amyloid-β 40/42 ratio. This alteration in amyloid-β isoform ratio occurs independently of a change in the carboxypeptidase activity of the γ-secretase complex, which cleaves the peptide from APP, or the rate of extracellular clearance of amyloid-β. These new mechanistic insights into the role of triplication of genes on chromosome 21, other than APP, in the development of Alzheimer's disease in individuals who have Down syndrome may have implications for the treatment of this common cause of neurodegeneration.
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http://dx.doi.org/10.1093/brain/awy159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6061702PMC
August 2018

Mice with endogenous TDP-43 mutations exhibit gain of splicing function and characteristics of amyotrophic lateral sclerosis.

EMBO J 2018 06 15;37(11). Epub 2018 May 15.

MRC Mammalian Genetics Unit, Harwell, UK

TDP-43 (encoded by the gene ) is an RNA binding protein central to the pathogenesis of amyotrophic lateral sclerosis (ALS). However, how mutations trigger pathogenesis remains unknown. Here, we use novel mouse mutants carrying point mutations in endogenous to dissect TDP-43 function at physiological levels both and Interestingly, we find that mutations within the C-terminal domain of TDP-43 lead to a gain of splicing function. Using two different strains, we are able to separate TDP-43 loss- and gain-of-function effects. TDP-43 gain-of-function effects in these mice reveal a novel category of splicing events controlled by TDP-43, referred to as "skiptic" exons, in which skipping of constitutive exons causes changes in gene expression. , this gain-of-function mutation in endogenous causes an adult-onset neuromuscular phenotype accompanied by motor neuron loss and neurodegenerative changes. Furthermore, we have validated the splicing gain-of-function and skiptic exons in ALS patient-derived cells. Our findings provide a novel pathogenic mechanism and highlight how TDP-43 gain of function and loss of function affect RNA processing differently, suggesting they may act at different disease stages.
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http://dx.doi.org/10.15252/embj.201798684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983119PMC
June 2018

Crystal structure of intraflagellar transport protein 80 reveals a homo-dimer required for ciliogenesis.

Elife 2018 04 16;7. Epub 2018 Apr 16.

Department of Molecular Biology and Genetics, Aarhus University, Aarhus, Denmark.

Oligomeric assemblies of intraflagellar transport (IFT) particles build cilia through sequential recruitment and transport of ciliary cargo proteins within cilia. Here we present the 1.8 Å resolution crystal structure of the IFT-B protein IFT80, which reveals the architecture of two N-terminal β-propellers followed by an α-helical extension. The N-terminal β-propeller tethers IFT80 to the IFT-B complex via IFT38 whereas the second β-propeller and the C-terminal α-helical extension result in IFT80 homo-dimerization. Using CRISPR/Cas to create biallelic frameshift mutations in IMCD3 mouse cells, we demonstrate that IFT80 is absolutely required for ciliogenesis. Structural mapping and rescue experiments reveal that human disease-causing missense mutations do not cluster within IFT80 and form functional IFT particles. Unlike missense mutant forms of IFT80, deletion of the C-terminal dimerization domain prevented rescue of ciliogenesis. Taken together our results may provide a first insight into higher order IFT complex formation likely required for IFT train formation.
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http://dx.doi.org/10.7554/eLife.33067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5931796PMC
April 2018

Inextensible Non-Rigid Structure-from-Motion by Second-Order Cone Programming.

IEEE Trans Pattern Anal Mach Intell 2018 10 13;40(10):2428-2441. Epub 2017 Oct 13.

We present a global and convex formulation for the template-less 3D reconstruction of a deforming object with the perspective camera. We show for the first time how to construct a Second-Order Cone Programming (SOCP) problem for Non-Rigid Structure-from-Motion (NRSfM) using the Maximum-Depth Heuristic (MDH). In this regard, we deviate strongly from the general trend of using affine cameras and factorization-based methods to solve NRSfM, which do not perform well with complex nonlinear deformations. In MDH, the points' depths are maximized so that the distance between neighbouring points in camera space are upper bounded by the geodesic distance. In NRSfM both geodesic and camera space distances are unknown. We show that, nonetheless, given point correspondences and the camera's intrinsics the whole problem can be solved with SOCP. This is the first convex formulation for NRSfM with physical constraints. We further present how robustness and temporal continuity can be included in the formulation to handle outliers and decrease the problem size, respectively. We show with extensive experiments that our methods accurately reconstruct quasi-isometric objects from partial views under articulated and strong deformations. Compared to the previous methods, our approach gives better or similar accuracy. It naturally handles missing correspondences, non-smooth objects and is very simple to implement compared to previous methods, with only one free parameter (the neighbourhood size).
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http://dx.doi.org/10.1109/TPAMI.2017.2762669DOI Listing
October 2018

Augmented reality in a tumor resection model.

Surg Endosc 2018 03 15;32(3):1192-1201. Epub 2017 Aug 15.

Department of Gynecologic Surgery, Clermont-Ferrand University Hospital Estaing, place Lucie et Raymond Aubrac, Clermont-Ferrand, France.

Background: Augmented Reality (AR) guidance is a technology that allows a surgeon to see sub-surface structures, by overlaying pre-operative imaging data on a live laparoscopic video. Our objectives were to evaluate a state-of-the-art AR guidance system in a tumor surgical resection model, comparing the accuracy of the resection with and without the system. Our system has three phases. Phase 1: using the MRI images, the kidney's and pseudotumor's surfaces are segmented to construct a 3D model. Phase 2: the intra-operative 3D model of the kidney is computed. Phase 3: the pre-operative and intra-operative models are registered, and the laparoscopic view is augmented with the pre-operative data.

Methods: We performed a prospective experimental study on ex vivo porcine kidneys. Alginate was injected into the parenchyma to create pseudotumors measuring 4-10 mm. The kidneys were then analyzed by MRI. Next, the kidneys were placed into pelvictrainers, and the pseudotumors were laparoscopically resected. The AR guidance system allows the surgeon to see tumors and margins using classical laparoscopic instruments, and a classical screen. The resection margins were measured microscopically to evaluate the accuracy of resection.

Results: Ninety tumors were segmented: 28 were used to optimize the AR software, and 62 were used to randomly compare surgical resection: 29 tumors were resected using AR and 33 without AR. The analysis of our pathological results showed 4 failures (tumor with positive margins) (13.8%) in the AR group, and 10 (30.3%) in the Non-AR group. There was no complete miss in the AR group, while there were 4 complete misses in the non-AR group. In total, 14 (42.4%) tumors were completely missed or had a positive margin in the non-AR group.

Conclusions: Our AR system enhances the accuracy of surgical resection, particularly for small tumors. Crucial information such as resection margins and vascularization could also be displayed.
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http://dx.doi.org/10.1007/s00464-017-5791-7DOI Listing
March 2018

Use of augmented reality in laparoscopic gynecology to visualize myomas.

Fertil Steril 2017 Mar 12;107(3):737-739. Epub 2017 Jan 12.

Department of Gynecologic Surgery, Centre Hospitalier de l'Université Estaing Clermont-Ferrand, Clermont-Ferrand, France; ALCoV, Image Science for Interventional Techniques (Unité Mixte de Recherche 6284, Centre National de la Recherche Scientifique), University of Auvergne, Clermont-Ferrand, France.

Objective: To report the use of augmented reality (AR) in gynecology.

Design: AR is a surgical guidance technology that enables important hidden surface structures to be visualized in endoscopic images. AR has been used for other organs, but never in gynecology and never with a very mobile organ like the uterus. We have developed a new AR approach specifically for uterine surgery and demonstrated its use for myomectomy.

Setting: Tertiary university hospital.

Patient(s): Three patients with one, two, and multiple myomas, respectively.

Intervention(s): AR was used during laparoscopy to localize the myomas.

Main Outcome Measure(s): Three-dimensional (3D) models of the patient's uterus and myomas were constructed before surgery from T2-weighted magnetic resonance imaging. The intraoperative 3D shape of the uterus was determined. These models were automatically aligned and "fused" with the laparoscopic video in real time.

Result(s): The live fused video made the uterus appear semitransparent, and the surgeon can see the location of the myoma in real time while moving the laparoscope and the uterus. With this information, the surgeon can easily and quickly decide on how best to access the myoma.

Conclusion(s): We developed an AR system for gynecologic surgery and have used it to improve laparoscopic myomectomy. Technically, the software we developed is very different to approaches tried for other organs, and it can handle significant challenges, including image blur, fast motion, and partial views of the organ.
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http://dx.doi.org/10.1016/j.fertnstert.2016.12.016DOI Listing
March 2017

Differential Contribution of Subunit Interfaces to α9α10 Nicotinic Acetylcholine Receptor Function.

Mol Pharmacol 2017 03 9;91(3):250-262. Epub 2017 Jan 9.

Instituto de Investigaciones en Ingeniería, Genética y Biología Molecular, Dr Héctor N Torres (J.C.B., I.M., M.M. L., M.M., P.V.P., A.B.E.), Instituto de Química Biológica (P.O.C.), and Instituto de Investigaciones Bioquímicas de Bahía Blanca (J.C., C.B), Consejo Nacional de Investigaciones Científicas y Técnicas, Buenos Aires, Argentina; Department of Neuroscience, Physiology and Pharmacology, University College London, United Kingdom (J.K.G.-T., T.C., N.S.M.); Departamento de Química Biológica Facultad de Ciencias Exactas y Naturales (P.O.C.), and Instituto de Farmacología, Facultad de Medicina (P.V.P., A.B.E.), Universidad de Buenos Aires, Buenos Aires, Argentina; and Departamento de Biología, Bioquímica y Farmacia, Universidad Nacional del Sur, Bahía Blanca, Argentina (J.C., C.B).

Nicotinic acetylcholine receptors can be assembled from either homomeric or heteromeric pentameric subunit combinations. At the interface of the extracellular domains of adjacent subunits lies the acetylcholine binding site, composed of a principal component provided by one subunit and a complementary component of the adjacent subunit. Compared with neuronal nicotinic acetylcholine cholinergic receptors (nAChRs) assembled from α and β subunits, the α9α10 receptor is an atypical member of the family. It is a heteromeric receptor composed only of α subunits. Whereas mammalian α9 subunits can form functional homomeric α9 receptors, α10 subunits do not generate functional channels when expressed heterologously. Hence, it has been proposed that α10 might serve as a structural subunit, much like a β subunit of heteromeric nAChRs, providing only complementary components to the agonist binding site. Here, we have made use of site-directed mutagenesis to examine the contribution of subunit interface domains to α9α10 receptors by a combination of electrophysiological and radioligand binding studies. Characterization of receptors containing Y190T mutations revealed unexpectedly that both α9 and α10 subunits equally contribute to the principal components of the α9α10 nAChR. In addition, we have shown that the introduction of a W55T mutation impairs receptor binding and function in the rat α9 subunit but not in the α10 subunit, indicating that the contribution of α9 and α10 subunits to complementary components of the ligand-binding site is nonequivalent. We conclude that this asymmetry, which is supported by molecular docking studies, results from adaptive amino acid changes acquired only during the evolution of mammalian α10 subunits.
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http://dx.doi.org/10.1124/mol.116.107482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5325082PMC
March 2017

Planar Structure-from-Motion with Affine Camera Models: Closed-Form Solutions, Ambiguities and Degeneracy Analysis.

IEEE Trans Pattern Anal Mach Intell 2017 06 8;39(6):1237-1255. Epub 2016 Jun 8.

ALCoV-ISIT (CNRS), Université d'Auvergne, Clermont Ferrand, France.

Planar Structure-from-Motion (SfM) is the problem of reconstructing a planar object or surface from a set of 2D images using motion information. The problem is well-understood with the perspective camera model and can be solved with Homography Decomposition (HD). However when the structure is small and/or viewed far from the camera the perspective effects diminish, and in the limit the projections become affine. In these situations HD fails because the problem itself becomes ill-posed. We propose a stable alternative using affine camera models. These have been used extensively to reconstruct non-planar structures, however a general, accurate and closed-form method for planar structures has been missing. The problem is fundamentally different with planar structures because the types of affine camera models one can use are more restricted and it is inherently more ambiguous and non-linear. We provide a closed-form method for the orthographic camera model that solves the general problem (three or more views with three or more correspondences and missing correspondences) and returns all metric structure solutions and corresponding camera poses. The method does not require initialisation, and optimises an objective function that is very similar to the reprojection error. In fact there is no clear benefit in refining its solutions with bundle adjustment, which is a remarkable result. We also present a new theoretical analysis that deepens our understanding of the problem. The main result is the necessary and sufficient geometric conditions for the problem to be degenerate with the orthographic camera. We also show there can exist up to two solutions for metric structure with four or more views (previously it was assumed to be unique), and we give the necessary and sufficient geometric conditions for disambiguation. Other theoretical results include showing that in the case of three images the optimal reconstruction (with respect to reprojection error) can usually be found in closed-form, and additional prior knowledge needed to solve with non-orthographic affine cameras.
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http://dx.doi.org/10.1109/TPAMI.2016.2578333DOI Listing
June 2017

A Stable Analytical Framework for Isometric Shape-from-Template by Surface Integration.

IEEE Trans Pattern Anal Mach Intell 2017 05 4;39(5):833-850. Epub 2016 May 4.

Shape-from-Template (SfT) reconstructs the shape of a deforming surface from a single image, a 3D template and a deformation prior. For isometric deformations, this is a well-posed problem. However, previous methods which require no initialization break down when the perspective effects are small, which happens when the object is small or viewed from larger distances. That is, they do not handle all projection geometries. We propose stable SfT methods that accurately reconstruct the 3D shape for all projection geometries. We follow the existing approach of using first-order differential constraints and obtain local analytical solutions for depth and the first-order quantities: the depth-gradient or the surface normal. Previous methods use the depth solution directly to obtain the 3D shape. We prove that the depth solution is unstable when the projection geometry tends to affine, while the solution for the first-order quantities remain stable for all projection geometries. We therefore propose to solve SfT by first estimating the first-order quantities (either depth-gradient or surface normal) and integrating them to obtain shape. We validate our approach with extensive synthetic and real-world experiments and obtain significantly more accurate results compared to previous initialization-free methods. Our approach does not require any optimization, which makes it very fast.
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http://dx.doi.org/10.1109/TPAMI.2016.2562622DOI Listing
May 2017

Augmented reality in gynecologic surgery: evaluation of potential benefits for myomectomy in an experimental uterine model.

Surg Endosc 2017 01 29;31(1):456-461. Epub 2016 Apr 29.

Department of Gynecological Surgery, CHU Clermont Ferrand, 1 Place Lucie Aubrac, 63000, Clermont-Ferrand, France.

Background: Augmented Reality (AR) is a technology that can allow a surgeon to see subsurface structures. This works by overlaying information from another modality, such as MRI and fusing it in real time with the endoscopic images. AR has never been developed for a very mobile organ like the uterus and has never been performed for gynecology. Myomas are not always easy to localize in laparoscopic surgery when they do not significantly change the surface of the uterus, or are at multiple locations.

Objective: To study the accuracy of myoma localization using a new AR system compared to MRI-only localization.

Methods: Ten residents were asked to localize six myomas (on a uterine model into a laparoscopic box) when either using AR or in conditions that simulate a standard method (only the MRI was available). Myomas were randomly divided in two groups: the control group (MRI only, AR not activated) and the AR group (AR activated). Software was used to automatically measure the distance between the point of contact on the uterine surface and the myoma. We compared these distances to the true shortest distance to obtain accuracy measures. The time taken to perform the task was measured, and an assessment of the complexity was performed.

Results: The mean accuracy in the control group was 16.80 mm [0.1-52.2] versus 0.64 mm [0.01-4.71] with AR. In the control group, the mean time to perform the task was 18.68 [6.4-47.1] s compared to 19.6 [3.9-77.5] s with AR. The mean score of difficulty (evaluated for each myoma) was 2.36 [1-4] versus 0.87 [0-4], respectively, for the control and the AR group.

Discussion: We developed an AR system for a very mobile organ. This is the first user study to quantitatively evaluate an AR system for improving a surgical task. In our model, AR improves localization accuracy.
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http://dx.doi.org/10.1007/s00464-016-4932-8DOI Listing
January 2017

Shape-from-Template.

IEEE Trans Pattern Anal Mach Intell 2015 Oct;37(10):2099-118

We study a problem that we call Shape-from-Template, which is the problem of reconstructing the shape of a deformable surface from a single image and a 3D template. Current methods in the literature address the case of isometric deformations, and relax the isometry constraint to the convex inextensibility constraint, solved using the so-called maximum depth heuristic. We call these methods zeroth-order since they use image point locations (the zeroth-order differential structure) to solve the shape inference problem from a perspective image. We propose a novel class of methods that we call first-order. The key idea is to use both image point locations and their first-order differential structure. The latter can be easily extracted from a warp between the template and the input image. We give a unified problem formulation as a system of PDEs for isometric and conformal surfaces that we solve analytically. This has important consequences. First, it gives the first analytical algorithms to solve this type of reconstruction problems. Second, it gives the first algorithms to solve for the exact constraints. Third, it allows us to study the well-posedness of this type of reconstruction: we establish that isometric surfaces can be reconstructed unambiguously and that conformal surfaces can be reconstructed up to a few discrete ambiguities and a global scale. In the latter case, the candidate solution surfaces are obtained analytically. Experimental results on simulated and real data show that our isometric methods generally perform as well as or outperform state of the art approaches in terms of reconstruction accuracy, while our conformal methods largely outperform all isometric methods for extensible deformations.
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http://dx.doi.org/10.1109/TPAMI.2015.2392759DOI Listing
October 2015

Automatic Detection of the Uterus and Fallopian Tube Junctions in Laparoscopic Images.

Inf Process Med Imaging 2015 ;24:552-63

We present a method for the automatic detection of the uterus and the Fallopian tube/Uterus junctions (FU-junctions) in a monocular laparoscopic image. The main application is to perform automatic registration and fusion between preoperative radiological images of the uterus and laparoscopic images for image-guided surgery. In the broader context of computer assisted intervention, our method is the first that detects an organ and registration landmarks from laparoscopic images without manual input. Our detection problem is challenging because of the large inter-patient anatomical variability and pathologies such as uterine fibroids. We solve the problem using learned contextual geometric constraints that statistically model the positions and orientations of the FU-junctions relative to the uterus' body. We train the uterus detector using a modern part-based approach and the FU-junction detector using junction-specific context-sensitive features. We have trained and tested on a database of 95 uterus images with cross validation, and successfully detected the uterus with Recall = 0.95 and average Number of False Positives per Image (NFPI) = 0.21, and FU-junctions with Recall = 0.80 and NFPI = 0.50. Our experimental results show that the contextual constraints are fundamental to achieve high quality detection.
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http://dx.doi.org/10.1007/978-3-319-19992-4_43DOI Listing
September 2015

Screening a UK amyotrophic lateral sclerosis cohort provides evidence of multiple origins of the C9orf72 expansion.

Neurobiol Aging 2015 Jan 1;36(1):546.e1-7. Epub 2014 Aug 1.

Department of Neurodegenerative Disease, University College London, Queen Square, London, UK; MRC Centre for Neuromuscular Diseases, University College London, Queen Square, London, UK. Electronic address:

An expanded hexanucleotide repeat in the C9orf72 gene is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (C9ALS/FTD). Although 0-30 hexanucleotide repeats are present in the general population, expansions >500 repeats are associated with C9ALS/FTD. Large C9ALS/FTD expansions share a common haplotype and whether these expansions derive from a single founder or occur more frequently on a predisposing haplotype is yet to be determined and is relevant to disease pathomechanisms. Furthermore, although cases carrying 50-200 repeats have been described, their role and the pathogenic threshold of the expansions remain to be identified and carry importance for diagnostics and genetic counseling. We present clinical and genetic data from a UK ALS cohort and report the detailed molecular study of an atypical somatically unstable expansion of 90 repeats. Our results across different tissues provide evidence for the pathogenicity of this repeat number by showing they can somatically expand in the central nervous system to the well characterized pathogenic range. Our results support the occurrence of multiple expansion events for C9ALS/FTD.
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http://dx.doi.org/10.1016/j.neurobiolaging.2014.07.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270445PMC
January 2015

Correlation of clinical and molecular features in spinal bulbar muscular atrophy.

Neurology 2014 Jun 9;82(23):2077-84. Epub 2014 May 9.

From the Department of Neurodegenerative Disease (P.F., L.M., T.C., E.M.C.F.), Sobell Department of Motor Neuroscience and Movement Disorders (N.N., L.G.), and MRC Centre for Neuromuscular Disease (P.F., N.N., I.S., A.C., E.M.C.F., L.G., M.G.H.), UCL Institute of Neurology, Queen Square, London; Neurogenetics Unit (S.P.), National Hospital for Neurology and Neurosurgery, Queen Square, London; and Centre for Neuroscience & Trauma (A.M.), Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, UK.

Objectives: To characterize the clinical and genetic features of spinal bulbar muscular atrophy (SBMA), a rare neurodegenerative disorder caused by the expansion of a CAG repeat in the first exon of the androgen receptor gene, in the United Kingdom.

Methods: We created a national register for SBMA in the United Kingdom and recruited 61 patients between 2005 and 2013. In our cross-sectional study, we assessed, by direct questioning, impairment of activities of daily living (ADL) milestones, functional rating, and subjective disease impact, and performed correlations with both CAG repeat size and degree of somatic mosaicism. Ten patients were deceased, 46 patients participated in the study, and 5 declined.

Results: Subjects had an average age at onset of 43.4 years, and weakness onset most frequently occurred in the lower limbs (87%). Impaired mobility was the most frequently reported problem by patients, followed by bulbar dysfunction. Age distribution of the impairment of ADL milestones showed remarkable overlap with a Japanese study. We have identified a significant correlation between the number of CAG repeats and both age at onset and ADL milestones. Somatic mosaicism also showed a correlation with CAG expansion size and age at onset.

Conclusions: Clinical features in SBMA show a substantial overlap when comparing populations with different genetic backgrounds. This finding has major implications, because multicenter trials will be necessary to obtain sufficient power in future clinical trials. Clinical-genetic correlations are strong in SBMA and should inform any clinical research strategy in this condition.
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http://dx.doi.org/10.1212/WNL.0000000000000507DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4075620PMC
June 2014

Profilin1 E117G is a moderate risk factor for amyotrophic lateral sclerosis.

J Neurol Neurosurg Psychiatry 2014 May 5;85(5):506-8. Epub 2013 Dec 5.

MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, , London, UK.

Background: Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are progressive neurodegenerative disorders that share significant clinical, pathological and genetic overlap and are considered to represent different ends of a common disease spectrum. Mutations in Profilin1 have recently been described as a rare cause of familial ALS. The PFN1 E117G missense variant has been described in familial and sporadic cases, and also found in controls, casting doubt on its pathogenicity. Interpretation of such variants represents a significant clinical-genetics challenge.

Objective And Results: Here, we combine a screen of a new cohort of 383 ALS patients with multiple-sequence datasets to refine estimates of the ALS and FTD risk associated with PFN1 E117G. Together, our cohorts add up to 5118 ALS and FTD cases and 13 089 controls. We estimate a frequency of E117G of 0.11% in controls and 0.25% in cases. Estimated odds after population stratification is 2.44 (95% CI 1.048 to ∞, Mantel-Haenszel test p=0.036).

Conclusions: Our results show an association between E117G and ALS, with a moderate effect size.
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http://dx.doi.org/10.1136/jnnp-2013-306761DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3995330PMC
May 2014

Sequencing analysis of the spinal bulbar muscular atrophy CAG expansion reveals absence of repeat interruptions.

Neurobiol Aging 2014 Feb 13;35(2):443.e1-3. Epub 2013 Sep 13.

Department of Neurodegenerative Disease, UCL Institute of Neurology, Queen Square, London, UK; MRC Centre for Neuromuscular Disease, UCL Institute of Neurology, Queen Square, London, UK. Electronic address:

Trinucleotide repeat disorders are a heterogeneous group of diseases caused by the expansion, beyond a pathogenic threshold, of unstable DNA tracts in different genes. Sequence interruptions in the repeats have been described in the majority of these disorders and may influence disease phenotype and heritability. Spinal bulbar muscular atrophy (SBMA) is a motor neuron disease caused by a CAG trinucleotide expansion in the androgen receptor (AR) gene. Diagnostic testing and previous research have relied on fragment analysis polymerase chain reaction to determine the AR CAG repeat size, and have therefore not been able to assess the presence of interruptions. We here report a sequencing study of the AR CAG repeat in a cohort of SBMA patients and control subjects in the United Kingdom. We found no repeat interruptions to be present, and we describe differences between sequencing and traditional sizing methods.
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http://dx.doi.org/10.1016/j.neurobiolaging.2013.07.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3898077PMC
February 2014

3D reconstruction in laparoscopy with close-range photometric stereo.

Med Image Comput Comput Assist Interv 2012 ;15(Pt 2):634-42

ALCoV-ISIT, CNRS and Université d'Auvergne, Clermont-Ferrand, France.

In this paper we present the first solution to 3D reconstruction in monocular laparoscopy using methods based on Photometric Stereo (PS). Our main contributions are to provide the new theory and practical solutions to successfully apply PS in close-range imaging conditions. We are specifically motivated by a solution with minimal hardware modification to existing laparoscopes. In fact the only physical modification we make is to adjust the colour of the laparoscope's illumination via three colour filters placed at its tip. Once calibrated, our approach can compute 3D from a single image, does not require correspondence estimation, and computes absolute depth densely. We demonstrate the potential of our approach with ground truth ex-vivo and in-vivo experimentation.
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http://dx.doi.org/10.1007/978-3-642-33418-4_78DOI Listing
January 2013

Computer assisted minimally invasive surgery: is medical computer vision the answer to improving laparosurgery?

Med Hypotheses 2012 Dec 1;79(6):858-63. Epub 2012 Oct 1.

Advanced Laparoscopy and Computer Vision, Université d'Auvergne, Clermont-Ferrand, France.

Minimally Invasive Surgery (MIS) is one of the most effective methods of modern surgical intervention that has considerable advantages compared with open surgery, including reduced trauma, pain, and post-operative recovery time. MIS has improved substantially over the years, chiefly due to new hardware innovations, including HD cameras and flexible head endoscopes. However, MIS continues to be hindered by several problems. In addition to hardware innovation, Computer Vision (CV) has been proposed as a way to overcome some of its current limitations. However, the research literature lacks a coherent picture of how the limitations can be best overcome by hardware, CV or a combination of the two. In this paper we focus on laparoscopic MIS, and list these limitations into 5 clear categories. We detail the effectiveness of hardware and CV solutions with respect to each limitation, from which we base the following hypothesis: CV is both complementary and necessary to hardware development, to overcome all 5 limitations in laparoscopy. Our paper is of value to laparoscopy surgeons, by conveying what is expected to be achieved in computer-aided laparoscopy over the next decade. It is also of value to medical CV researchers, by clarifying which problems are best solved with CV, in light of the hardware developments likely to occur over the next decade.
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http://dx.doi.org/10.1016/j.mehy.2012.09.007DOI Listing
December 2012

A nicotinic acetylcholine receptor transmembrane point mutation (G275E) associated with resistance to spinosad in Frankliniella occidentalis.

J Neurochem 2013 Mar 13;124(5):590-601. Epub 2013 Jan 13.

Department of Neuroscience, Physiology & Pharmacology, University College London, London, UK.

High levels of resistance to spinosad, a macrocyclic lactone insecticide, have been reported previously in western flower thrips, Frankliniella occidentalis, an economically important insect pest of vegetables, fruit and ornamental crops. We have cloned the nicotinic acetylcholine receptor (nAChR) α6 subunit from F. occidentalis (Foα6) and compared the nucleotide sequence of Foα6 from susceptible and spinosad-resistant insect populations (MLFOM and R1S respectively). A single nucleotide change has been identified in Foα6, resulting in the replacement of a glycine (G) residue in susceptible insects with a glutamic acid (E) in resistant insects. The resistance-associated mutation (G275E) is predicted to lie at the top of the third α-helical transmembrane domain of Foα6. Although there is no direct evidence identifying the location of the spinosad binding site, the analogous amino acid in the C. elegans glutamate-gated chloride channel lies in close proximity (4.4 Å) to the known binding site of ivermectin, another macrocyclic lactone pesticide. The functional consequences of the resistance-associated mutation have been examined in the human nAChR α7 subunit. Introduction of an analogous (A272E) mutation in α7 abolishes the modulatory effects of spinosad whilst having no significant effect upon activation by acetylcholine, consistent with spinosad having an allosteric mechanism of action.
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http://dx.doi.org/10.1111/jnc.12029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644170PMC
March 2013

The Drosophila nicotinic acetylcholine receptor subunits Dα5 and Dα7 form functional homomeric and heteromeric ion channels.

BMC Neurosci 2012 Jun 22;13:73. Epub 2012 Jun 22.

Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.

Background: Nicotinic acetylcholine receptors (nAChRs) play an important role as excitatory neurotransmitters in vertebrate and invertebrate species. In insects, nAChRs are the site of action of commercially important insecticides and, as a consequence, there is considerable interest in examining their functional properties. However, problems have been encountered in the successful functional expression of insect nAChRs, although a number of strategies have been developed in an attempt to overcome such difficulties. Ten nAChR subunits have been identified in the model insect Drosophila melanogaster (Dα1-Dα7 and Dβ1-Dβ3) and a similar number have been identified in other insect species. The focus of the present study is the Dα5, Dα6 and Dα7 subunits, which are distinguished by their sequence similarity to one another and also by their close similarity to the vertebrate α7 nAChR subunit.

Results: A full-length cDNA clone encoding the Drosophila nAChR Dα5 subunit has been isolated and the properties of Dα5-, Dα6- and Dα7-containing nAChRs examined in a variety of cell expression systems. We have demonstrated the functional expression, as homomeric nAChRs, of the Dα5 and Dα7 subunits in Xenopus oocytes by their co-expression with the molecular chaperone RIC-3. Also, using a similar approach, we have demonstrated the functional expression of a heteromeric 'triplet' nAChR (Dα5 + Dα6 + Dα7) with substantially higher apparent affinity for acetylcholine than is seen with other subunit combinations. In addition, specific cell-surface binding of [125I]-α-bungarotoxin was detected in both Drosophila and mammalian cell lines when Dα5 was co-expressed with Dα6 and RIC-3. In contrast, co-expression of additional subunits (including Dα7) with Dα5 and Dα6 prevented specific binding of [125I]-α-bungarotoxin in cell lines, suggesting that co-assembly with other nAChR subunits can block maturation of correctly folded nAChRs in some cellular environments.

Conclusion: Data are presented demonstrating the ability of the Drosophila Dα5 and Dα7 subunits to generate functional homomeric and also heteromeric nAChRs.
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http://dx.doi.org/10.1186/1471-2202-13-73DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3444433PMC
June 2012