Imaging outcome measures for progressive multiple sclerosis trials

Imaging markers that are reliable, reproducible and sensitive to neurodegenerative changes in progressive multiple sclerosis (MS) can enhance the development of new medications with a neuroprotective mode-of-action. Accordingly, in recent years, a considerable number of imaging biomarkers have been included in phase 2 and 3 clinical trials in primary and secondary progressive MS. Brain lesion count and volume are markers of inflammation and demyelination and are important outcomes even in progressive MS trials. Brain and, more recently, spinal cord atrophy are gaining relevance, considering their strong association with disability accrual; ongoing improvements in analysis methods will enhance their applicability in clinical trials, especially for cord atrophy. Advanced magnetic resonance imaging (MRI) techniques (e.g. magnetization transfer ratio (MTR), diffusion tensor imaging (DTI), spectroscopy) have been included in few trials so far and hold promise for the future, as they can reflect specific pathological changes targeted by neuroprotective treatments. Position emission tomography (PET) and optical coherence tomography have yet to be included. Applications, limitations and future perspectives of these techniques in clinical trials in progressive MS are discussed, with emphasis on measurement sensitivity, reliability and sample size calculation

Spinal cord atrophy in a primary progressive multiple sclerosis trial: Improved sample size using GBSI

Background: We aimed to evaluate the implications for clinical trial design of the generalised boundary-shift integral (GBSI) for spinal cord atrophy measurement. / Methods: We included 220 primary-progressive multiple sclerosis patients from a phase 2 clinical trial, with baseline and week-48 3DT1-weighted MRI of the brain and spinal cord (1 × 1 × 1 mm3), acquired separately. We obtained segmentation-based cross-sectional spinal cord area (CSA) at C1-2 (from both brain and spinal cord MRI) and C2-5 levels (from spinal cord MRI) using DeepSeg, and, then, we computed corresponding GBSI. / Results: Depending on the spinal cord segment, we included 67.4–98.1% patients for CSA measurements, and 66.9–84.2% for GBSI. Spinal cord atrophy measurements obtained with GBSI had lower measurement variability, than corresponding CSA. Looking at the image noise floor, the lowest median standard deviation of the MRI signal within the cerebrospinal fluid surrounding the spinal cord was found on brain MRI at the C1-2 level. Spinal cord atrophy derived from brain MRI was related to the corresponding measures from dedicated spinal cord MRI, more strongly for GBSI than CSA. Spinal cord atrophy measurements using GBSI, but not CSA, were associated with upper and lower limb motor progression. / Discussion: Notwithstanding the reduced measurement variability, the clinical correlates, and the possibility of using brain acquisitions, spinal cord atrophy using GBSI should remain a secondary outcome measure in MS studies, until further advancements increase the quality of acquisition and reliability of processing

Towards realistic laparoscopic image generation using image-domain translation

Background and ObjectivesOver the last decade, Deep Learning (DL) has revolutionized data analysis in many areas, including medical imaging. However, there is a bottleneck in the advancement of DL in the surgery field, which can be seen in a shortage of large-scale data, which in turn may be attributed to the lack of a structured and standardized methodology for storing and analyzing surgical images in clinical centres. Furthermore, accurate annotations manually added are expensive and time consuming. A great help can come from the synthesis of artificial images; in this context, in the latest years, the use of Generative Adversarial Neural Networks (GANs) achieved promising results in obtaining photo-realistic images. MethodsIn this study, a method for Minimally Invasive Surgery (MIS) image synthesis is proposed. To this aim, the generative adversarial network pix2pix is trained to generate paired annotated MIS images by transforming rough segmentation of surgical instruments and tissues into realistic images. An additional regularization term was added to the original optimization problem, in order to enhance realism of surgical tools with respect to the background. Results Quantitative and qualitative (i.e., human-based) evaluations of generated images have been carried out in order to assess the effectiveness of the method. ConclusionsExperimental results show that the proposed method is actually able to translate MIS segmentations to realistic MIS images, which can in turn be used to augment existing data sets and help at overcoming the lack of useful images; this allows physicians and algorithms to take advantage from new annotated instances for their training

Polyphenols as potential agents in the management of temporomandibular disorders

Temporomandibular disorders (TMD) consist of multifactorial musculoskeletal disorders associated with the muscles of mastication, temporomandibular joint (TMJ), and annexed structures. This clinical condition is characterized by temporomandibular pain, restricted mandibular movement, and TMJ synovial inflammation, resulting in reduced quality of life of affected people. Commonly, TMD management aims to reduce pain and inflammation by using pharmacologic therapies that show efficacy in pain relief but their long-term use is frequently associated with adverse effects. For this reason, the use of natural compounds as an effective alternative to conventional drugs appears extremely interesting. Indeed, polyphenols could represent a potential therapeutic strategy, related to their ability to modulate the inflammatory responses involved in TMD. The present work reviews the mechanisms underlying inflammation-related TMD, highlighting the potential role of polyphenols as a promising approach to develop innovative management of temporomandibular diseases

Generalised boundary shift integral for longitudinal assessment of spinal cord atrophy

Spinal cord atrophy measurements obtained from structural magnetic resonance imaging (MRI) are associated with disability in many neurological diseases and serve as in vivo biomarkers of neurodegeneration. Longitudinal spinal cord atrophy rate is commonly determined from the numerical difference between two volumes (based on 3D surface fitting) or two cross-sectional areas (CSA, based on 2D edge detection) obtained at different time-points. Being an indirect measure, atrophy rates are susceptible to variable segmentation errors at the edge of the spinal cord. To overcome those limitations, we developed a new registration-based pipeline that measures atrophy rates directly. We based our approach on the generalised boundary shift integral (GBSI) method, which registers 2 scans and uses a probabilistic XOR mask over the edge of the spinal cord, thereby measuring atrophy more accurately than segmentation-based techniques. Using a large cohort of longitudinal spinal cord images (610 subjects with multiple sclerosis from a multi-centre trial and 52 healthy controls), we demonstrated that GBSI is a sensitive, quantitative and objective measure of longitudinal spinal cord volume change. The GBSI pipeline is repeatable, reproducible, and provides more precise measurements of longitudinal spinal cord atrophy than segmentation-based methods in longitudinal spinal cord atrophy studies