Ratthaporn Boonsuth1, Rebecca S. Samson1, Amy R. McDowell2, Philippa Bridgen3,4,5, Peter J Lally4,6,7, John S. Thornton8,9, Claudia A. M. Gandini Wheeler-Kingshott1,10,11, and Marios C. Yiannakas1
1NMR Research Unit, Queen Square MS Centre, Department of Neuroinflammation, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom, 2Queen Square Centre for Neuromuscular Diseases, University College London, London, United Kingdom, 3Biomedical Engineering Department, School of Biomedical Engineering and Imaging Sciences, King's College London, London, United Kingdom, 4London Collaborative Ultra high field System (LoCUS), London, UK, Kings College London, London, United Kingdom, 5Guys and St Thomas’ NHS Foundation Trust, Kings College London, London, United Kingdom, 6Department of Bioengineering, Imperial College London, London, United Kingdom, 7Centre for Care Research and Technology, UK Dementia Research Institute, London, United Kingdom, 8Neuroradiological Academic Unit, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom, 9Lysholm Department of Neuroradiology, National Hospital for Neurology and Neurosurgery, London, United Kingdom, 10Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy, 11Digital Neuroscience Centre, IRCCS Mondino Foundation, Pavia, Italy
Synopsis
Keywords: Peripheral Nerves, Diffusion Tensor Imaging, Magnetization Transfer
Motivation: Quantitative and semi-quantitative magnetic resonance imaging investigations of the peripheral nerves in vivo using 7 Tesla are currently limited.
Goal(s): To obtain standard diffusion tensor imaging (DTI) metrics and magnetization transfer ratio (MTR) in the healthy tibial nerve in vivo and to assess the reproducibility of these measures.
Approach: Reproducibility was assessed through repeated measurements (scan-rescan) and calculation of the coefficient of variation between measurements.
Results: The reproducibility assessment results are presented along with normative DTI and MTR measures in the tibial nerve, which can serve as reference in future studies of pathological conditions affecting the lower peripheral nerves.
Impact: This pilot study demonstrates the feasibility of
using 7 Tesla magnetic resonance imaging to assess the healthy tibial nerve in
vivo using diffusion-weighted and magnetization transfer imaging, opening
up the possibilities to investigate lower peripheral neuropathies with higher
spatial resolution.
Introduction
Magnetic
resonance imaging (MRI) has been used successfully for assessing the peripheral
nervous system (PNS) in a number of pathological conditions affecting the
peripheral nerves. However, studies have been hampered by various technical
factors, mainly related to the small size of the peripheral nerves1-3. High-field 7 Tesla (T)
MRI offers inherently enhanced signal-to-noise ratio and contrast-to-noise
ratio, compared to lower field strength MRI systems2,4, thus enabling imaging
with superior spatial resolution. The value of combining conventional
anatomical MRI with quantitative and semi-quantitative MRI methods such as diffusion
tensor imaging (DTI) and magnetization transfer ratio (MTR) for assessing the peripheral
nerves has previously been demonstrated in several studies using lower magnetic
field strength, such as 3T MRI. However, similar investigations using 7T MRI
are limited, with only a few studies so far reporting results from assessments of
the upper extremity nerves5-7. Given the
limited number of studies using 7T MRI to assess the PNS at various anatomical
locations, coupled with the fact that the lower extremity nerves are also
damaged in a number of pathological conditions8,9, this pilot study aimed to assess the reproducibility of DTI
and MTR measurements in the tibial nerve of healthy volunteers and to determine
normative values to serve as reference in future investigations of pathological
conditions affecting the lower peripheral nerves. Methods
Participants: Six healthy
volunteers (2 females, mean age 38.8 years, range 27-49 years) were recruited. The
study was approved by the local review board and informed consent was obtained
from all study participants. As part of the reproducibility assessment, half of
the participants (N=3/6) returned for a re-scan session at least one week after
their first scan.
MR imaging: Imaging was performed using a 7T MRI system
(MAGNETOM Terra, Siemens Healthcare, Erlangen, Germany). Each participant had
their right ankle imaged in the feet-first supine position using the 1Tx/28Rx RAPID
knee coil (https://www.rapidbiomed.de/). High-resolution T1-weighted (T1w) and quantitative
double-echo steady-state (qDESS10,11) sequences were acquired in the axial plane for high-resolution
anatomical imaging. DTI was performed using readout-segmented echo-planar
imaging. MTR data was collected both with and without magnetization transfer
saturation pulses using a 3D multi-echo gradient-echo sequence. Details of the acquisition
parameters used are shown in Table 1.
Image analysis: The tibial nerve was manually segmented in
FSLview (http://www.fmrib.ox.ac.uk/fsl/) using the images from the first qDESS echo, resulting in binary masks
for each image slice. The qDESS images and masks were resampled to match the
DTI and MTR image resolution, aligned and registered with the NiftyReg
registration toolkit12. Diffusion-weighted data were fitted using Dipy13,14 to obtain standard DTI metrics of
axial, radial, mean diffusivity (AD, RD, MD, respectively) and fractional
anisotropy (FA) in two different ways, to account for the range of b-values used in
previously published reports in the upper extremities5,15, using: set-a) b=0 and b=700 s/mm2
and set-b) b=0 and b=1200 s/mm2. MTR was calculated from the on- and
off-resonance acquisitions. To evaluate scan-rescan reproducibility, the same
rater performed tibial nerve segmentation on the images obtained from both scan
sessions. The mean and standard deviation (±SD) of MTR and DTI measures were calculated across all participants. The percent coefficient of variation (%COV) was calculated to determine the scan-rescan
reproducibility.Results
Example maps of DTI
metrics (AD, RD, MD, and FA) for set-a) and set-b), and MTR maps are shown in
Figure 1. Table 2 presents mean (±SD) MTR and DTI measures across all 6
participants. Table 3 displays the scan-rescan reproducibility as %COV for each
MRI-derived measure separately.Discussion and Conclusion
This pilot study
demonstrates the feasibility of using 7T high-resolution anatomical MRI
combined with DTI and MTR to assess the healthy tibial nerve in vivo.
DTI and MTR measures were in line with existing literature5-7. Moreover, they were obtained
with sufficiently high reproducibility, as demonstrated by the low scan-rescan %COV
values (worst case scenario: %COV=16.1%), indicative of the 7T potential value of
detecting subtle changes in nerve composition and microstructure with high
spatial resolution, otherwise not possible in clinically feasible times on
standard 1.5T/3T MRI. Future investigations in a larger sample population will be
required to verify the reproducibility results obtained in this study and to
determine the potential role of these measures (with the use of 7T MRI) in characterizing
pathological conditions affecting the peripheral nerves. Acknowledgements
This work using 7T MRI is supported by
the Wellcome
Trust Collaboration in Science grant [WT201526/Z/16/Z]. RB receives a
scholarship from Chiang Mai University, Chiang Mai, Thailand. RS receives
funding from the BRC (BRC1130/HEI/RS/11041). PJL receives funding from The
Wellcome Trust (220473/Z/20/Z), The Edmond J Safra Foundation, NIHR Imperial
BRC, and NIH (R01EB002524). CGWK receives funding from Horizon 2020 (Research
and Innovation Action Grants Human Brain Project 945539 (SGA3)), BRC
(#BRC704/CAP/CGW), MRC (#MR/S026088/1), Ataxia UK, Rosetrees Trust
(#PGL22/100041 and #PGL21/10079). CGWK is a shareholder in Queen Square
Analytics Ltd. MCY received
funding from the National Brain Appeal’s Innovation Fund (https://www.nationalbrainappeal.org/).References
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