Introduction

Quantitative MRI, measuring tissue parameters such as T2, diffusivity, and fat fraction, can complement conventional anatomical MR images in radiological assessment by providing quantitative biomarkers to monitor disease severity and progression. Applied in the peripheral nervous system, such biomarkers could potentially allow more effective evaluation of treatment efficacy in nerve diseases such as Charcot-Marie-Tooth Type 1A (CMT1A) syndrome. Obtaining such information at high resolution with a single scan sequence could provide a powerful tool for assessing nerve disease while retaining a simple workflow. In this work, we demonstrate the feasibility of using the Double-Echo in Steady-State (DESS) sequence for high-resolution anatomic imaging at 7 Tesla with an in-plane resolution of under 0.15 mm, while also obtaining quantitative maps of T2, the apparent diffusion coefficient (ADC), and fat fraction. Furthermore, we compare the resulting measurements in patients with CMT1A neurological disease to age- and biological sex-matched healthy controls.

Methods

Axial 3D DESS scans were acquired in the lower right thigh of 6 CMT1A subjects (2M/4F) and 6 healthy controls, individually biological sex- and age-matched to the patients (having the same age within a margin of +/-5 years). The scans were performed at a field strength of 7 Tesla (Terra, Siemens Healthineers USA) with a 28-channel knee coil (QED), with scan parameters as shown in Figure 1. In the DESS sequence, two echoes are acquired before and after a spoiler gradient, as shown in Figure 2^1,2. The first echo has T1/T2 contrast while the second echo predominantly has a T2 contrast and diffusion contrast if the spoiler gradient moment is large enough to act as a diffusion gradient. We ran the sequence three times, each time acquiring and reconstructing both echoes as two separate images: First, it was run with a small-moment spoiler gradient that gave minimal diffusion contrast. By comparing the relative intensities of the two echoes to numerical signal models, a T2 estimate was obtained³. Fat was suppressed by using a water-selective binomial pulse. Next, the sequence was run again with a large spoiler gradient moment. Comparing the results to the low-moment signals gave an ADC estimate³. Finally, the sequence was run again but with a fat-selective binomial pulse. Comparing the results to the first scan gave a fat fraction estimate. This fat fraction measurement was not performed in two of the patients due to time constraints. In the quantitative maps of T2, ADC, and fat fraction thus obtained, regions of interest (ROI) were drawn in each nerve fascicle in the sciatic nerve in a slice just above its bifurcation, and in the tibial and fibular nerves in a slice 1 cm below the bifurcation, and the measurements in each ROI recorded. Fat shift was corrected in post-processing by shifting the resulting image to match the water-based image. Statistical significance was estimated with two-sided t-tests with α = 0.05.

Results

Sample images from a healthy control are shown in Figure 3. Individual fascicles are clearly visible, and maps of their T2, ADC, and fat fraction values can be easily assessed. Figure 4 shows the results for the two different populations. The cross-sectional area, T2, ADC, and fat fraction have been measured in each fascicle and the results averaged for each patient and each control. Figure 5 further summarizes this data, showing the mean values in the sciatic, tibial, and fibular nerves in all fascicles of all patients and controls. The cross-sectional area, T2, and ADC were all visually observed to be higher in patients than in healthy controls, although only the cross-sectional area was measured to have a statistically significant difference, with p < 0.005 in the sciatic and fibular nerves and p < 0.01 in the tibial nerve. A difference in the fat fraction was not observed.

Discussion

The results demonstrate the feasibility of acquiring high-SNR anatomic and quantitative images in peripheral nerves at below 0.15 mm in-plane resolution using the DESS sequence. Further, the results indicate a larger cross-sectional area, T2, and ADC in the fascicles of CMT1A subjects compared to healthy controls, which is in agreement with prior studies^4,5. The lack of observed differences in fat fraction could be an artifact of the small patient population for this parameter (4 patients) and needs to be studied further.

Conclusion

The DESS sequence can be used to obtain high-resolution anatomic and quantitative images of peripheral nerves at 7T, yielding measurements that can potentially help differentiate between nerves in CMT1A patients and healthy nerves.

Acknowledgements

Imaging was performed at the Athinoula A. Martinos Center for Biomedical Imaging at the Massachusetts General Hospital using resources provided by the Center for Functional Neuroimaging Technologies (P41EB015896) and the Center for Mesoscale Mapping (P41EB030006), Biotechnology Resource Grants supported by the National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health (NIH). The NIH also provided support through grants K99AG066815, R01EB027779, R01EB028797, and S10OD023637. This research was also supported in part by the MGH/HST Athinoula A. Martinos Center for Biomedical Imaging. Siemens Healthineers provided technical support.

References

[1] Bruder MRM 1988; [2] Redpath MRM 1988; [3] Staroswiecki MRM 2012; [4] Vaeggemose Muscle and Nerve 2017; [5] Maeda Muscle and Nerve 2021