Spinal cord gray matter segmentation using deep dilated convolutions

Gray matter (GM) tissue changes have been associated with a wide range of neurological disorders and was also recently found relevant as a biomarker for disability in amyotrophic lateral sclerosis. The ability to automatically segment the GM is, therefore, an important task for modern studies of the spinal cord. In this work, we devise a modern, simple and end-to-end fully automated human spinal cord gray matter segmentation method using Deep Learning, that works both on in vivo and ex vivo MRI acquisitions. We evaluate our method against six independently developed methods on a GM segmentation challenge and report state-of-the-art results in 8 out of 10 different evaluation metrics as well as major network parameter reduction when compared to the traditional medical imaging architectures such as U-Nets.Comment: 13 pages, 8 figure

Spinal cord volume quantification and clinical application in multiple sclerosis

Magnetic resonance imaging of the spinal cord is a valuable part of the diagnostic work-up in patients with multiple sclerosis and other neurological disorders. Currently, mainly signal intensity changes within the cord in MR-images are considered in the clinical management of disorders of the central nervous system. However, cross-sectional or longitudinal measurements of spinal cord volume may deliver additional valuable information. Hence, the overall goal of this doctoral thesis was twofold: i) to clinically validate methods for quantification of spinal cord volume and spinal cord compartments, which are suitable for longitudinal assessment of large patient cohorts and clinical practice and ii) to evaluate spinal cord volume as a potential valuable biomarker and provide new insights into the role of spinal cord damage in multiple sclerosis. The first part focuses on the validation of quantification methods for spinal cord volume and includes two projects. While several MRI-based approaches of semi- and fully automatic techniques for volumetric spinal cord measurements have been proposed, up to now no gold standard exists and only a few methods have been validated and/or evaluated on patient follow-up scans to demonstrate their applicability in longitudinal settings. One of the latter segmentation methods was recently developed in-house and showed excellent reliability for cervical cord segmentation (Cordial, the cord image analyzer). In a first project, we extended its applicability to the lumbar cord, since no other software has been tested so far within this anatomical region of interest. On a well-selected dataset of 10 healthy controls (scanned in a scan-rescan fashion) we were able to show that - even within this technically challenging region - this segmentation algorithm provides excellent inter- and intra-session reproducibility showing high potential for application in longitudinal trials. In a second project, we aimed at obtaining volumetric information on particular compartments of the spinal cord such as the cord grey and white matter, since recent studies in multiple sclerosis provided evidence that measuring spinal cord grey matter volume changes may be a better biomarker for disease progression than quantifying cord white matter pathology or even volumetric brain measures. We therefore implemented a novel imaging approach, the averaged magnetization inversion recovery acquisitions sequence, for better grey and white matter visualization within the cord and scanned 24 healthy controls in a scan-rescan fashion. Further we applied an innovative fully automatic variational segmentation algorithm with a shape prior modified for 3D data with a slice similarity prior to segment the spinal cord grey and white matter. This pipeline allowed for highly accurate and reproducible grey and white matter segmentation within the cord. In view of its features, our automatic segmentation method seems promising for further application in both cross-sectional and longitudinal and in large multi-center studies. The second goal of this thesis was the clinical application of the above-mentioned methods for the evaluation of spinal cord volume changes as a potential biomarker in multiple sclerosis patients. For this purpose, we quantified spinal cord volume change in a large cohort of 243 multiple sclerosis patients, followed over a period of 6 years with annual clinical and MRI examinations. Spinal cord volume proved to be a strong predictor of physical disability and disease progression, indicating that it may be a suitable marker for monitoring disease activity and severity in all disease types but especially in progressive multiple sclerosis. Spinal cord volume also proved to be the only MRI metric to strongly explain the clinical progression over time as opposed to brain atrophy and lesion measures

[¹⁸F]fluorination of biorelevant arylboronic acid pinacol ester scaffolds synthesized by convergence techniques

Aim: The development of small molecules through convergent multicomponent reactions (MCR) has been boosted during the last decade due to the ability to synthesize, virtually without any side-products, numerous small drug-like molecules with several degrees of structural diversity.(1) The association of positron emission tomography (PET) labeling techniques in line with the “one-pot” development of biologically active compounds has the potential to become relevant not only for the evaluation and characterization of those MCR products through molecular imaging, but also to increase the library of radiotracers available. Therefore, since the [18F]fluorination of arylboronic acid pinacol ester derivatives tolerates electron-poor and electro-rich arenes and various functional groups,(2) the main goal of this research work was to achieve the 18F-radiolabeling of several different molecules synthesized through MCR. Materials and Methods: [18F]Fluorination of boronic acid pinacol esters was first extensively optimized using a benzaldehyde derivative in relation to the ideal amount of Cu(II) catalyst and precursor to be used, as well as the reaction solvent. Radiochemical conversion (RCC) yields were assessed by TLC-SG. The optimized radiolabeling conditions were subsequently applied to several structurally different MCR scaffolds comprising biologically relevant pharmacophores (e.g. β-lactam, morpholine, tetrazole, oxazole) that were synthesized to specifically contain a boronic acid pinacol ester group. Results: Radiolabeling with fluorine-18 was achieved with volumes (800 μl) and activities (≤ 2 GBq) compatible with most radiochemistry techniques and modules. In summary, an increase in the quantities of precursor or Cu(II) catalyst lead to higher conversion yields. An optimal amount of precursor (0.06 mmol) and Cu(OTf)2(py)4 (0.04 mmol) was defined for further reactions, with DMA being a preferential solvent over DMF. RCC yields from 15% to 76%, depending on the scaffold, were reproducibly achieved. Interestingly, it was noticed that the structure of the scaffolds, beyond the arylboronic acid, exerts some influence in the final RCC, with electron-withdrawing groups in the para position apparently enhancing the radiolabeling yield. Conclusion: The developed method with high RCC and reproducibility has the potential to be applied in line with MCR and also has a possibility to be incorporated in a later stage of this convergent “one-pot” synthesis strategy. Further studies are currently ongoing to apply this radiolabeling concept to fluorine-containing approved drugs whose boronic acid pinacol ester precursors can be synthesized through MCR (e.g. atorvastatin)

EVA London 2022: Electronic Visualisation and the Arts

The Electronic Visualisation and the Arts London 2022 Conference (EVA London 2022) is co-sponsored by the Computer Arts Society (CAS) and BCS, the Chartered Institute for IT, of which the CAS is a Specialist Group. Of course, this has been a difficult time for all conferences, with the Covid-19 pandemic. For the first time since 2019, the EVA London 2022 Conference is a physical conference. It is also an online conference, as it was in the previous two years. We continue with publishing the proceedings, both online, with open access via ScienceOpen, and also in our traditional printed form, for the second year in full colour. Over recent decades, the EVA London Conference on Electronic Visualisation and the Arts has established itself as one of the United Kingdom’s most innovative and interdisciplinary conferences. It brings together a wide range of research domains to celebrate a diverse set of interests, with a specialised focus on visualisation. The long and short papers in this volume cover varied topics concerning the arts, visualisations, and IT, including 3D graphics, animation, artificial intelligence, creativity, culture, design, digital art, ethics, heritage, literature, museums, music, philosophy, politics, publishing, social media, and virtual reality, as well as other related interdisciplinary areas. The EVA London 2022 proceedings presents a wide spectrum of papers, demonstrations, Research Workshop contributions, other workshops, and for the seventh year, the EVA London Symposium, in the form of an opening morning session, with three invited contributors. The conference includes a number of other associated evening events including ones organised by the Computer Arts Society, Art in Flux, and EVA International. As in previous years, there are Research Workshop contributions in this volume, aimed at encouraging participation by postgraduate students and early-career artists, accepted either through the peer-review process or directly by the Research Workshop chair. The Research Workshop contributors are offered bursaries to aid participation. In particular, EVA London liaises with Art in Flux, a London-based group of digital artists. The EVA London 2022 proceedings includes long papers and short “poster” papers from international researchers inside and outside academia, from graduate artists, PhD students, industry professionals, established scholars, and senior researchers, who value EVA London for its interdisciplinary community. The conference also features keynote talks. A special feature this year is support for Ukrainian culture after its invasion earlier in the year. This publication has resulted from a selective peer review process, fitting as many excellent submissions as possible into the proceedings. This year, submission numbers were lower than previous years, mostly likely due to the pandemic and a new requirement to submit drafts of long papers for review as well as abstracts. It is still pleasing to have so many good proposals from which to select the papers that have been included. EVA London is part of a larger network of EVA international conferences. EVA events have been held in Athens, Beijing, Berlin, Brussels, California, Cambridge (both UK and USA), Canberra, Copenhagen, Dallas, Delhi, Edinburgh, Florence, Gifu (Japan), Glasgow, Harvard, Jerusalem, Kiev, Laval, London, Madrid, Montreal, Moscow, New York, Paris, Prague, St Petersburg, Thessaloniki, and Warsaw. Further venues for EVA conferences are very much encouraged by the EVA community. As noted earlier, this volume is a record of accepted submissions to EVA London 2022. Associated online presentations are in general recorded and made available online after the conference