Clinical Applications for Diffusion MRI and Tractography of Cranial Nerves Within the Posterior Fossa: A Systematic Review

Objective: This paper presents a systematic review of diffusion MRI (dMRI) and tractography of cranial nerves within the posterior fossa. We assess the effectiveness of the diffusion imaging methods used and examine their clinical applications. / Methods: The Pubmed, Web of Science and EMBASE databases were searched from January 1st 1997 to December 11th 2017 to identify relevant publications. Any study reporting the use of diffusion imaging and/or tractography in patients with confirmed cranial nerve pathology was eligible for selection. Study quality was assessed using the Methodological Index for Non-Randomized Studies (MINORS) tool. / Results: We included 41 studies comprising 16 studies of patients with trigeminal neuralgia (TN), 22 studies of patients with a posterior fossa tumor and three studies of patients with other pathologies. Most acquisition protocols used single-shot echo planar imaging (88%) with a single b-value of 1,000 s/mm2 (78%) but there was significant variation in the number of gradient directions, in-plane resolution, and slice thickness between studies. dMRI of the trigeminal nerve generated interpretable data in all cases. Analysis of diffusivity measurements found significantly lower fractional anisotropy (FA) values within the root entry zone of nerves affected by TN and FA values were significantly lower in patients with multiple sclerosis. Diffusivity values within the trigeminal nerve correlate with the effectiveness of surgical treatment and there is some evidence that pre-operative measurements may be predictive of treatment outcome. Fiber tractography was performed in 30 studies (73%). Most studies evaluating fiber tractography involved patients with a vestibular schwannoma (82%) and focused on generating tractography of the facial nerve to assist with surgical planning. Deterministic tractography using diffusion tensor imaging was performed in 93% of cases but the reported success rate and accuracy of generating fiber tracts from the acquired diffusion data varied considerably. / Conclusions: dMRI has the potential to inform our understanding of the microstructural changes that occur within the cranial nerves in various pathologies. Cranial nerve tractography is a promising technique but new avenues of using dMRI should be explored to optimize and improve its reliability

DeepReg: a deep learning toolkit for medical image registration

Image fusion is a fundamental task in medical image analysis and computer-assisted intervention. Medical image registration, computational algorithms that align different images together (Hill et al., 2001), has in recent years turned the research attention towards deep learning. Indeed, the representation ability to learn from population data with deep neural networks has opened new possibilities for improving registration generalisability by mitigating difficulties in designing hand-engineered image features and similarity measures for many realworld clinical applications (Fu et al., 2020; Haskins et al., 2020). In addition, its fast inference can substantially accelerate registration execution for time-critical tasks. DeepReg is a Python package using TensorFlow (Abadi et al., 2015) that implements multiple registration algorithms and a set of predefined dataset loaders, supporting both labelledand unlabelled data. DeepReg also provides command-line tool options that enable basic and advanced functionalities for model training, prediction and image warping. These implementations, together with their documentation, tutorials and demos, aim to simplify workflows for prototyping and developing novel methodology, utilising latest development and accessing quality research advances. DeepReg is unit tested and a set of customised contributor guidelines are provided to facilitate community contributions. A submission to the MICCAI Educational Challenge has utilised the DeepReg code and demos to explore the link between classical algorithms and deep-learning-based methods (Montana Brown et al., 2020), while a recently published research work investigated temporal changes in prostate cancer imaging, by using a longitudinal registration adapted from the DeepReg code (Yang et al., 2020)

Systematic review of methods used in meta-analyses where a primary outcome is an adverse or unintended event

addresses: Peninsula College of Medicine and Dentistry, St Luke's Campus, University of Exeter, Exeter, UK. [email protected]: PMCID: PMC3528446types: Journal Article; Research Support, Non-U.S. Gov't© 2012 Warren et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Adverse consequences of medical interventions are a source of concern, but clinical trials may lack power to detect elevated rates of such events, while observational studies have inherent limitations. Meta-analysis allows the combination of individual studies, which can increase power and provide stronger evidence relating to adverse events. However, meta-analysis of adverse events has associated methodological challenges. The aim of this study was to systematically identify and review the methodology used in meta-analyses where a primary outcome is an adverse or unintended event, following a therapeutic intervention

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

The importance of group-wise registration in tract based spatial statistics study of neurodegeneration: a simulation study in Alzheimer's disease.

Tract-based spatial statistics (TBSS) is a popular method for the analysis of diffusion tensor imaging data. TBSS focuses on differences in white matter voxels with high fractional anisotropy (FA), representing the major fibre tracts, through registering all subjects to a common reference and the creation of a FA skeleton. This work considers the effect of choice of reference in the TBSS pipeline, which can be a standard template, an individual subject from the study, a study-specific template or a group-wise average. While TBSS attempts to overcome registration error by searching the neighbourhood perpendicular to the FA skeleton for the voxel with maximum FA, this projection step may not compensate for large registration errors that might occur in the presence of pathology such as atrophy in neurodegenerative diseases. This makes registration performance and choice of reference an important issue. Substantial work in the field of computational anatomy has shown the use of group-wise averages to reduce biases while avoiding the arbitrary selection of a single individual. Here, we demonstrate the impact of the choice of reference on: (a) specificity (b) sensitivity in a simulation study and (c) a real-world comparison of Alzheimer's disease patients to controls. In (a) and (b), simulated deformations and decreases in FA were applied to control subjects to simulate changes of shape and WM integrity similar to what would be seen in AD patients, in order to provide a "ground truth" for evaluating the various methods of TBSS reference. Using a group-wise average atlas as the reference outperformed other references in the TBSS pipeline in all evaluations

Downregulation of erythropoietin receptor by overexpression of phospholipase C-gamma 1 is critical for decrease on focal adhesion in transformed cells

Background Phospholipase C-gamma 1 (PLC-gamma 1) is known to play a critical role in cell adhesion and migration and is highly expressed in metastatic tumors. In the current study, we found that cells transformed by PLC-gamma 1 overexpression (PLC-gamma 1 cells) exhibited a marked decrease in expression of the Epo receptor (EpoR). Here, we assessed the role of EpoR-dependent signaling pathways in PLC-gamma 1-dependent regulation of cell adhesion and migration. Methods Expression and phosphorylation of EpoR and its functional role in PLC-gamma 1 cells were evaluated by immunoblot analysis or cell adhesion assay. The mechanism for PLC-gamma 1-induced EpoR downregulation was analyzed by blockage of proteosomal degradation with MG132. EpoR expression was also confirmed in colorectal cancer tissues in which PLC-gamma 1 was highly expressed. Results EpoR was present on rat fibroblasts, where it functionally active and capable of increasing cell adhesion and migratory activity. However, PLC-gamma 1 cells significantly decreased the Epo-dependent effects via ubiquitination-proteosomal degradation of EpoR. A marked decrease of EpoR expression was confirmed in colorectal cancer tissues that showed high-level of PLC-gamma 1 expression. Conclusion The Epo/EpoR complex plays a critical role in the adhesion and migration of rat fibroblasts, and its functional inactivation is associated with PLC-gamma 1-dependent reduction of cell-matrix adhesion and this also affects cell migration.close