Beyond Crossing Fibers: Bootstrap Probabilistic Tractography Using Complex Subvoxel Fiber Geometries

Diffusion magnetic resonance imaging fiber tractography is a powerful tool for investigating human white matter connectivity in vivo. However, it is prone to false positive and false negative results, making interpretation of the tractography result difficult. Optimal tractography must begin with an accurate description of the subvoxel white matter fiber structure, includes quantification of the uncertainty in the fiber directions obtained, and quantifies the confidence in each reconstructed fiber tract. This paper presents a novel and comprehensive pipeline for fiber tractography that meets the above requirements. The subvoxel fiber geometry is described in detail using a technique that allows not only for straight crossing fibers but for fibers that curve and splay. This technique is repeatedly performed within a residual bootstrap statistical process in order to efficiently quantify the uncertainty in the subvoxel geometries obtained. A robust connectivity index is defined to quantify the confidence in the reconstructed connections. The tractography pipeline is demonstrated in the human brain

Correcting for T1 bias in Magnetization Transfer Saturation (MTsat) Maps Using Sparse-MP2RAGE

Purpose: Magnetization transfer saturation (MTsat) mapping is commonly used to examine the macromolecular content of brain tissue. This study compared variable flip angle (VFA) T1 mapping against compressed sensing (cs)MP2RAGE T1 mapping for accelerating MTsat imaging. Methods: VFA, MP2RAGE and csMP2RAGE were compared against inversion recovery (IR) T1 in a phantom at 3 Tesla. The same 1 mm VFA, MP2RAGE and csMP2RAGE protocols were acquired in four healthy subjects to compare the resulting T1 and MTsat. Bloch-McConnell simulations were used to investigate differences between the phantom and in vivo T1 results. Finally, ten healthy controls were imaged twice with the csMP2RAGE MTsat protocol to quantify repeatability. Results: The MP2RAGE and csMP2RAGE protocols were 13.7% and 32.4% faster than the VFA protocol, respectively. All approaches provided accurate T1 values (<5% difference) in the phantom, but the accuracy of the T1 times was more impacted by differences in T2 for VFA than for MP2RAGE. In vivo, VFA generated longer T1 times than MP2RAGE and csMP2RAGE. Simulations suggest that the bias in the T1 values between VFA and IR-based approaches (MP2RAGE and IR) could be explained by the MT-effects from the inversion pulse. In the test-retest experiment, we found that the csMP2RAGE has a minimum detectable change of 3% for T1 mapping and 7.9% for MTsat imaging. Conclusions: We demonstrated that csMP2RAGE can be used in place of VFA T1 mapping in an MTsat protocol. Furthermore, a shorter scan time and high repeatability can be achieved using the csMP2RAGE sequence.Comment: 23 pages, 7 figures, 2 table

Optimization of acquisition parameters for cortical inhomogeneous magnetization transfer (ihMT) imaging using a rapid gradient echo readout

Purpose: Imaging biomarkers with increased myelin specificity are needed to better understand the complex progression of neurological disorders. Inhomogeneous magnetization transfer (ihMT) imaging is an emergent technique that has a high degree of specificity for myelin content but suffers from low signal-to-noise ratio (SNR). This study used simulations to determine optimal sequence parameters for ihMT imaging for use in high-resolution cortical mapping. Methods: MT-weighted cortical image intensity and ihMT SNR were simulated using modified Bloch equations for a range of sequence parameters. The acquisition time was limited to 4.5 min/volume. A custom MT-weighted RAGE sequence with center-out k-space encoding was used to enhance SNR at 3 Tesla. Pulsed MT imaging was studied over a range of saturation parameters and the impact of the turbo-factor on effective ihMT was investigated. 1 mm isotropic ihMTsat maps were generated in 25 healthy adults using an optimized protocol. Results: Greater SNR was observed for larger number of bursts consisting of 6-8 saturation pulses each, combined with a high readout turbo-factor. However, that protocol suffered from a point spread function that was more than twice the nominal resolution. For high-resolution cortical imaging, we selected a protocol with a higher effective resolution at the cost of a lower SNR. We present the first group-average ihMTsat whole-brain map at 1 mm isotropic resolution. Conclusion: This study presents the impact of saturation and excitation parameters on ihMTsat SNR and resolution. We demonstrate the feasibility of high-resolution cortical myelin imaging using ihMTsat in less than 20 minutes

Joint analysis of stressors and ecosystem services to enhance restoration effectiveness

With increasing pressure placed on natural systems by growing human populations, both scientists and resource managers need a better understanding of the relationships between cumulative stress from human activities and valued ecosystem services. Societies often seek to mitigate threats to these services through large-scale, costly restoration projects, such as the over one billion dollar Great Lakes Restoration Initiative currently underway. To help inform these efforts, we merged high-resolution spatial analyses of environmental stressors with mapping of ecosystem services for all five Great Lakes. Cumulative ecosystem stress is highest in near-shore habitats, but also extends offshore in Lakes Erie, Ontario, and Michigan. Variation in cumulative stress is driven largely by spatial concordance among multiple stressors, indicating the importance of considering all stressors when planning restoration activities. In addition, highly stressed areas reflect numerous different combinations of stressors rather than a single suite of problems, suggesting that a detailed understanding of the stressors needing alleviation could improve restoration planning. We also find that many important areas for fisheries and recreation are subject to high stress, indicating that ecosystem degradation could be threatening key services. Current restoration efforts have targeted high-stress sites almost exclusively, but generally without knowledge of the full range of stressors affecting these locations or differences among sites in service provisioning. Our results demonstrate that joint spatial analysis of stressors and ecosystem services can provide a critical foundation for maximizing social and ecological benefits from restoration investments. www.pnas.org/lookup/suppl/doi:10.1073/pnas.1213841110/-/DCSupplementa

A Temperature Phantom to Probe the Ensemble Average Propagator Asymmetry: an In-Silico Study

International audienceThe detection and quantification of asymmetry in the Ensemble Average Propagator (EAP) obtained from the Diffusion-Weighted (DW) signal has been shown only for theoretical models. EAP asymmetry appears for instance when diffusion occurs within fibers with particular geometries. However the quan-tification of EAP asymmetry corresponding to such geometries in controlled experimental conditions is limited by the difficulty of designing fiber geometries on a micrometer scale. To overcome this limitation we propose to adopt an alternative paradigm to induce asymmetry in the EAP. We apply a temperature gradient to a spinal cord tract to induce a corresponding diffusivity profile that alters locally the diffusion process to be asymmetric. We simulate the EAP and the corresponding complex DW signal in such a scenario. We quantify EAP asymmetry and investigate its relationship with the applied experimental conditions and with the acquisition parameters of a Pulsed Gradient Spin-Echo sequence. Results show that EAP asymmetry is sensible to the applied temperature-induced diffusivity gradient and that its quantification is influenced by the selected acquisition parameters

Q methodology and a Delphi poll: a useful approach to researching a narrative approach to therapy

Q methodology and a Delphi poll combined qualitative and quantitative methods to explore definitions of White and Epston's (1990) narrative approach to therapy among a group of UK practitioners. A Delphi poll was used to generate statements about narrative therapy. The piloting of statements by the Delphi panel identified agreement about theoretical ideas underpinning narrative therapy and certain key practices. A wider group of practitioners ranked the statements in a Q sort and made qualitative comments about their sorting. Quantitative methods (principal components analysis) were used to extract eight accounts of narrative therapy, five of which are qualitatively analysed in this paper. Agreement and differences were identified across a range of issues, including the social construction of narratives, privileging a political stance or narrative techniques and the relationship with other therapies, specifically systemic psychotherapy. Q methodology, combined with the Delphi poll, was a unique and innovative feature of this study

Feasibility of trial procedures for a randomised controlled trial of a community based group exercise intervention for falls prevention for visually impaired older people: the VIOLET study

Background Visually impaired older people (VIOP) have a higher risk of falling than their sighted peers, and are likely to avoid physical activity. The aim was to adapt the existing Falls Management Exercise (FaME) programme for VIOP, delivered in the community, and to investigate the feasibility of conducting a definitive randomised controlled trial (RCT) of this adapted intervention. Methods Two-centre randomised mixed methods pilot trial and economic evaluation of the adapted group-based FaME programme for VIOP versus usual care. A one hour exercise programme ran weekly over 12 weeks at the study sites (Newcastle and Glasgow), delivered by third sector (voluntary and community) organisations. Participants were advised to exercise at home for an additional two hours over the week. Those randomised to the usual activities group received no intervention. Outcome measures were completed at baseline, 12 and 24 weeks. The potential primary outcome was the Short Form Falls Efficacy Scale – International (SFES-I). Participants’ adherence was assessed by reviewing attendance records and self-reported compliance to the home exercises. Adherence with the course content (fidelity) by instructors was assessed by a researcher. Adverse events were collected in a weekly phone call. Results Eighteen participants, drawn from community-living VIOP were screened; 68 met the inclusion criteria; 64 participants were randomised with 33 allocated to the intervention and 31 to the usual activities arm. 94% of participants provided data at the 12 week visit and 92% at 24 weeks. Adherence was high. The intervention was found to be safe with 76% attending nine or more classes. Median time for home exercise was 50 min per week. There was little or no evidence that fear of falling, balance and falls risk, physical activity, emotional, attitudinal or quality of life outcomes differed between trial arms at follow-up. Conclusions The intervention, FaME, was implemented successfully for VIOP and all progression criteria for a main trial were met. The lack of difference between groups on fear of falling was unsurprising given it was a pilot study but there may have been other contributory factors including suboptimal exercise dose and apparent low risk of falls in participants. These issues need addressing for a future trial

Protocol for the development of guidance for stakeholder engagement in health and healthcare guideline development and implementation

Stakeholder engagement has become widely accepted as a necessary component of guideline development and implementation. While frameworks for developing guidelines express the need for those potentially affected by guideline recommendations to be involved in their development, there is a lack of consensus on how this should be done in practice. Further, there is a lack of guidance on how to equitably and meaningfully engage multiple stakeholders. We aim to develop guidance for the meaningful and equitable engagement of multiple stakeholders in guideline development and implementation. METHODS: This will be a multi-stage project. The first stage is to conduct a series of four systematic reviews. These will (1) describe existing guidance and methods for stakeholder engagement in guideline development and implementation, (2) characterize barriers and facilitators to stakeholder engagement in guideline development and implementation, (3) explore the impact of stakeholder engagement on guideline development and implementation, and (4) identify issues related to conflicts of interest when engaging multiple stakeholders in guideline development and implementation. DISCUSSION: We will collaborate with our multiple and diverse stakeholders to develop guidance for multi-stakeholder engagement in guideline development and implementation. We will use the results of the systematic reviews to develop a candidate list of draft guidance recommendations and will seek broad feedback on the draft guidance via an online survey of guideline developers and external stakeholders. An invited group of representatives from all stakeholder groups will discuss the results of the survey at a consensus meeting which will inform the development of the final guidance papers. Our overall goal is to improve the development of guidelines through meaningful and equitable multi-stakeholder engagement, and subsequently to improve health outcomes and reduce inequities in health

Charting the future of cancer health disparities research: A position statement from the American Association for Cancer Research, the American Cancer Society, the American Society of Clinical Oncology, and the National Cancer Institute

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138314/1/caac21404_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/138314/2/caac21404.pd