Towards in vivo g-ratio mapping using MRI: Unifying myelin and diffusion imaging

BACKGROUND: The g-ratio, quantifying the comparative thickness of the myelin sheath encasing an axon, is a geometrical invariant that has high functional relevance because of its importance in determining neuronal conduction velocity. Advances in MRI data acquisition and signal modelling have put in vivo mapping of the g-ratio, across the entire white matter, within our reach. This capacity would greatly increase our knowledge of the nervous system: how it functions, and how it is impacted by disease. NEW METHOD: This is the second review on the topic of g-ratio mapping using MRI. RESULTS: This review summarizes the most recent developments in the field, while also providing methodological background pertinent to aggregate g-ratio weighted mapping, and discussing pitfalls associated with these approaches. COMPARISON WITH EXISTING METHODS: Using simulations based on recently published data, this review reveals caveats to the state-of-the-art calibration methods that have been used for in vivo g-ratio mapping. It highlights the need to estimate both the slope and offset of the relationship between these MRI-based markers and the true myelin volume fraction if we are really to achieve the goal of precise, high sensitivity g-ratio mapping in vivo. Other challenges discussed in this review further evidence the need for gold standard measurements of human brain tissue from ex vivo histology. CONCLUSIONS: We conclude that the quest to find the most appropriate MRI biomarkers to enable in vivo g-ratio mapping is ongoing, with the full potential of many novel techniques yet to be investigated

Imperfect spoiling in variable flip angle T1 mapping at 7T: Quantifying and minimizing impact

PURPOSE: The variable flip angle (VFA) approach to T1 mapping assumes perfectly spoiled transverse magnetisation at the end of each repetition time (TR). Despite radiofrequency (RF) and gradient spoiling, this condition is rarely met, leading to erroneous T1 estimates ( T 1 app ). Theoretical corrections can be applied but make assumptions about tissue properties, for example, a global T2 time. Here, we investigate the effect of imperfect spoiling at 7T and the interaction between the RF and gradient spoiling conditions, additionally accounting for diffusion. We provide guidance on the optimal approach to maximise the accuracy of the T1 estimate in the context of 3D multi-echo acquisitions. METHODS: The impact of the spoiling regime was investigated through numerical simulations, phantom and in vivo experiments. RESULTS: The predicted dependence of T 1 app on tissue properties, system settings, and spoiling conditions was observed in both phantom and in vivo experiments. Diffusion effects modulated the dependence of T 1 app on both B 1 + efficiency and T2 times. CONCLUSION: Error in T 1 app can be minimized by using an RF spoiling increment and gradient spoiler moment combination that minimizes T2 -dependence and safeguards image quality. Although the diffusion effect was comparatively small at 7T, correction factors accounting for this effect are recommended

A mixed methods approach to evaluating community drug distributor performance in the control of neglected tropical diseases

BACKGROUND: Trusted literate, or semi-literate, community drug distributors (CDDs) are the primary implementers in integrated preventive chemotherapy (IPC) programmes for Neglected Tropical Disease (NTD) control. The CDDs are responsible for safely distributing drugs and for galvanising communities to repeatedly, often over many years, receive annual treatment, create and update treatment registers, monitor for side-effects and compile treatment coverage reports. These individuals are 'volunteers' for the programmes and do not receive remuneration for their annual work commitment. METHODS: A mixed methods approach, which included pictorial diaries to prospectively record CDD use of time, structured interviews and focus group discussions, was used to triangulate data on how 58 CDDs allocated their time towards their routine family activities and to NTD Programme activities in Uganda. The opportunity costs of CDD time were valued, performance assessed by determining the relationship between time and programme coverage, and CDD motivation for participating in the programme was explored. RESULTS: Key findings showed approximately 2.5 working weeks (range 0.6-11.4 working weeks) were spent on NTD Programme activities per year. The amount of time on NTD control activities significantly increased between the one and three deliveries that were required within an IPC campaign. CDD time spent on NTD Programme activities significantly reduced time available for subsistence and income generating engagements. As CDDs took more time to complete NTD Programme activities, their treatment performance, in terms of validated coverage, significantly decreased. Motivation for the programme was reported as low and CDDs felt undervalued. CONCLUSIONS: CDDs contribute a considerable amount of opportunity cost to the overall economic cost of the NTD Programme in Uganda due to the commitment of their time. Nevertheless, programme coverage of at least 75 %, as required by the World Health Organisation, is not being achieved and vulnerable individuals may not have access to treatment as a consequence of sub-optimal performance by the CDDs due to workload and programmatic factors

Physical activity and dietary behaviour in a population-based sample of British 10-year old children: the SPEEDY study (Sport, Physical activity and Eating behaviour: environmental Determinants in Young people).

BACKGROUND: The SPEEDY study was set up to quantify levels of physical activity (PA) and dietary habits and the association with potential correlates in 9-10 year old British school children. We present here the analyses of the PA, dietary and anthropometry data. METHODS: In a cross-sectional study of 2064 children (926 boys, 1138 girls) in Norfolk, England, we collected anthropometry data at school using standardised procedures. Body mass index (BMI) was used to define obesity status. PA was assessed with the Actigraph accelerometer over 7 days. A cut-off of > or = 2000 activity counts was used to define minutes of moderate-to-vigorous PA (MVPA). Dietary habits were assessed using the Health Behaviour in School Children food questionnaire. Weight status was defined using published international cut-offs (Cole, 2000). Differences between groups were assessed using independent t-tests for continuous data and chi-squared tests for categorical data. RESULTS: Valid PA data (>500 minutes per day on > or = 3 days) was available for 1888 children. Mean (+/- SD) activity counts per minute among boys and girls were 716.5 +/- 220.2 and 635.6 +/- 210.6, respectively (p < 0.001). Boys spent an average of 84.1 +/- 25.9 minutes in MVPA per day compared to 66.1 +/- 20.8 among girls (p < 0.001), with an average of 69.1% of children accumulating 60 minutes each day. The proportion of children classified as overweight and obese was 15.0% and 4.1% for boys and 19.3% and 6.6% for girls, respectively (p = 0.001). Daily consumption of at least one portion of fruit and of vegetables was 56.8% and 49.9% respectively, with higher daily consumption in girls than boys and in children from higher socioeconomic backgrounds. CONCLUSION: Results indicate that almost 70% of children meet national PA guidelines, indicating that a prevention of decline, rather than increasing physical activity levels, might be an appropriate intervention target. Promotion of daily fruit and vegetable intake in this age group is also warranted, possibly focussing on children from lower socioeconomic backgrounds.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Insights and improvements in correspondence between axonal volume fraction measured with diffusion-weighted MRI and electron microscopy

Biophysical diffusion-weighted imaging (DWI) models are increasingly used in neuroscience to estimate the axonal water fraction ((Formula presented.)), which in turn is key for noninvasive estimation of the axonal volume fraction ((Formula presented.)). These models require thorough validation by comparison with a reference method, for example, electron microscopy (EM). While EM studies often neglect the unmyelinated axons and solely report the fraction of myelinated axons, in DWI both myelinated and unmyelinated axons contribute to the DWI signal. However, DWI models often include simplifications, for example, the neglect of differences in the compartmental relaxation times or fixed diffusivities, which in turn might affect the estimation of (Formula presented.). We investigate whether linear calibration parameters (scaling and offset) can improve the comparability between EM- and DWI-based metrics of (Formula presented.). To this end, we (a) used six DWI models based on the so-called standard model of white matter (WM), including two models with fixed compartmental diffusivities (e.g., neurite orientation dispersion and density imaging, NODDI) and four models that fitted the compartmental diffusivities (e.g., white matter tract integrity, WMTI), and (b) used a multimodal data set including ex vivo diffusion DWI and EM data in mice with a broad dynamic range of fibre volume metrics. We demonstrated that the offset is associated with the volume fraction of unmyelinated axons and the scaling factor is associated with different compartmental (Formula presented.) and can substantially enhance the comparability between EM- and DWI-based metrics of (Formula presented.). We found that DWI models that fitted compartmental diffusivities provided the most accurate estimates of the EM-based (Formula presented.). Finally, we introduced a more efficient hybrid calibration approach, where only the offset is estimated but the scaling is fixed to a theoretically predicted value. Using this approach, a similar one-to-one correspondence to EM was achieved for WMTI. The method presented can pave the way for use of validated DWI-based models in clinical research and neuroscience

Robust 3D Bloch-Siegert based B 1 + mapping using multi-echo general linear modeling

PURPOSE: Quantitative MRI applications, such as mapping the T1 time of tissue, puts high demands on the accuracy and precision of transmit field ( B 1 + ) estimation. A candidate approach to satisfy these requirements exploits the difference in phase induced by the Bloch-Siegert frequency shift (BSS) of 2 acquisitions with opposite off-resonance frequency radiofrequency pulses. Interleaving these radiofrequency pulses ensures robustness to motion and scanner drifts; however, here we demonstrate that doing so also introduces a bias in the B 1 + estimates. THEORY AND METHODS: It is shown here by means of simulation and experiments that the amplitude of the error depends on MR pulse sequence parameters, such as repetition time and radiofrequency spoiling increment, but more problematically, on the intrinsic properties, T1 and T2 , of the investigated tissue. To solve these problems, a new approach to BSS-based B 1 + estimation that uses a multi-echo acquisition and a general linear model to estimate the correct BSS-induced phase is presented. RESULTS: In line with simulations, phantom and in vivo experiments confirmed that the general linear model-based method removed the dependency on tissue properties and pulse sequence settings. CONCLUSION: The general linear model-based method is recommended as a more accurate approach to BSS-based B 1 + mapping

Transcranial direct current stimulation with functional magnetic resonance imaging: a detailed validation and operational guide [version 1; peer review: 1 approved with reservations]

Introduction: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique used to modulate human brain and behavioural function in both research and clinical interventions. The combination of functional magnetic resonance imaging (fMRI) with tDCS enables researchers to directly test causal contributions of stimulated brain regions, answering questions about the physiology and neural mechanisms underlying behaviour. Despite the promise of the technique, advances have been hampered by technical challenges and methodological variability between studies, confounding comparability/replicability. / Methods: Here tDCS-fMRI at 3T was developed for a series of experiments investigating language recovery after stroke. To validate the method, one healthy volunteer completed an fMRI paradigm with three conditions: (i) No-tDCS, (ii) Sham-tDCS, (iii) 2mA Anodal-tDCS. MR data were analysed in SPM12 with region-of-interest (ROI) analyses of the two electrodes and reference sites. / Results: Quality assessment indicated no visible signal dropouts or distortions introduced by the tDCS equipment. After modelling scanner drift, motion-related variance, and temporal autocorrelation, we found no field inhomogeneity in functional sensitivity metrics across conditions in grey matter and in the three ROIs. / Discussion: Key safety factors and risk mitigation strategies that must be taken into consideration when integrating tDCS into an fMRI environment are outlined. To obtain reliable results, we provide practical solutions to technical challenges and complications of the method. It is hoped that sharing these data and SOP will promote methodological replication in future studies, enhancing the quality of tDCS-fMRI application, and improve the reliability of scientific results in this field. / Conclusions: The method and data provided here provide a technically safe, reliable tDCS-fMRI procedure to obtain high quality MR data. The detailed framework of the Standard Operation Procedure SOP (https://doi.org/10.5281/zenodo.4606564) systematically reports the technical and procedural elements of our tDCS-fMRI approach, which we hope can be adopted and prove useful in future studies

Robust 3D Bloch-Siegert based B 1 + mapping using multi-echo general linear modeling

PURPOSE: Quantitative MRI applications, such as mapping the T1 time of tissue, puts high demands on the accuracy and precision of transmit field ( B 1 + ) estimation. A candidate approach to satisfy these requirements exploits the difference in phase induced by the Bloch-Siegert frequency shift (BSS) of 2 acquisitions with opposite off-resonance frequency radiofrequency pulses. Interleaving these radiofrequency pulses ensures robustness to motion and scanner drifts; however, here we demonstrate that doing so also introduces a bias in the B 1 + estimates. THEORY AND METHODS: It is shown here by means of simulation and experiments that the amplitude of the error depends on MR pulse sequence parameters, such as repetition time and radiofrequency spoiling increment, but more problematically, on the intrinsic properties, T1 and T2 , of the investigated tissue. To solve these problems, a new approach to BSS-based B 1 + estimation that uses a multi-echo acquisition and a general linear model to estimate the correct BSS-induced phase is presented. RESULTS: In line with simulations, phantom and in vivo experiments confirmed that the general linear model-based method removed the dependency on tissue properties and pulse sequence settings. CONCLUSION: The general linear model-based method is recommended as a more accurate approach to BSS-based B 1 + mapping

Mitigating susceptibility-induced distortions in high-resolution 3DEPI fMRI at 7T

Geometric distortion is a major limiting factor for spatial specificity in high-resolution fMRI using EPI readouts and is exacerbated at higher field strengths due to increased B0 field inhomogeneity. Prominent correction schemes are based on B0 field-mapping or acquiring reverse phase-encoded (reversed-PE) data. However, to date, comparisons of these techniques in the context of fMRI have only been performed on 2DEPI data, either at lower field or lower resolution. In this study, we investigate distortion compensation in the context of sub-millimetre 3DEPI data at 7T. B0 field-mapping and reversed-PE distortion correction techniques were applied to both partial coverage BOLD-weighted and whole brain MT-weighted 3DEPI data with matched distortion. Qualitative assessment showed overall improvement in cortical alignment for both correction techniques in both 3DEPI fMRI and whole-brain MT-3DEPI datasets. The distortion-corrected MT-3DEPI images were quantitatively evaluated by comparing cortical alignment with an anatomical reference using dice coefficient (DC) and correlation ratio (CR) measures. These showed that B0 field-mapping and reversed-PE methods both improved correspondence between the MT-3DEPI and anatomical data, with more substantial improvements consistently obtained using the reversed-PE approach. Regional analyses demonstrated that the largest benefit of distortion correction, and in particular of the reversed-PE approach, occurred in frontal and temporal regions where susceptibility-induced distortions are known to be greatest, but had not led to complete signal dropout. In conclusion, distortion correction based on reversed-PE data has shown the greater capacity for achieving faithful alignment with anatomical data in the context of high-resolution fMRI at 7T using 3DEPI

Neuroimaging in Leber Hereditary Optic Neuropathy: State-of-the-art and future prospects

Leber Hereditary Optic Neuropathy (LHON) is an inherited mitochondrial retinal disease that causes the degeneration of retinal ganglion cells and leads to drastic loss of visual function. In the last decades, there has been a growing interest in using Magnetic Resonance Imaging (MRI) to better understand mechanisms of LHON beyond the retina. This is partially due to the emergence of gene-therapies for retinal diseases, and the accompanying expanded need for reliably quantifying and monitoring visual processing and treatment efficiency in patient populations. This paper aims to draw a current picture of key findings in this field so far, the challenges of using neuroimaging methods in patients with LHON, and important open questions that MRI can help address about LHON disease mechanisms and prognoses, including how downstream visual brain regions are affected by the disease and treatment and why, and how scope for neural plasticity in these pathways may limit or facilitate recovery