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Quantitative assessment of the degeneration of the superior cerebellar peduncle in Friedreich’s ataxia at 7 T: susceptibility, diffusion anisotropy, and T2 and T1 relaxometry
Sina Straub1, Julian Emmerich1,2, Stephanie Mangesius3, Elisabetta Indelicato4, Mark E. Ladd1,2,5, Sylvia Boesch4, and Elke R. Gizewski3

1Division of Medical Physics in Radiology, German Cancer Research Center, Heidelberg, Germany, 2Faculty of Physics and Astronomy, Heidelberg University, Heidelberg, Germany, 3Department of Neuroradiology, Medical University Innsbruck, Innsbruck, Austria, 4Department of Neurology, Medical University Innsbruck, Innsbruck, Austria, 5Faculty of Medicine, Heidelberg University, Heidelberg, Germany

Synopsis

Friedreich’s ataxia is a rare disease involving degenerative processes within white matter fiber tracts, spinal nerves and the cerebellum. A correlation of patients’ clinical status and superior cerebellar peduncle atrophy has been shown in MR volumetry studies. The ongoing ultra-high field study presented here assesses the degeneration of the superior cerebellar peduncle in Friedreich’s ataxia with quantitative MR parameters – susceptibility, diffusion anisotropy, and T2 and T1 relaxometry. Statistically significant differences between fractional anisotropy as well as T2 values in patients and healthy controls could be observed, indicating that these quantitative MRI methods potentially provide valuable biomarkers to assess the course of Friedreich’s ataxia.

INTRODUCTION

Despite the fact that Friedreich’s ataxia is a rare disease, it is the most common inherited ataxia with early onset of clinical manifestations.1 A correlation of superior cerebellar peduncle (SCP) atrophy and patients’ clinical status has been shown in magnetic resonance imaging (MRI) studies assessing SCP volume.2,3 However, pathological white matter changes in Friedreich’s ataxia have not been assessed using quantitative MRI methods such as relaxometry, susceptibility mapping and diffusion tensor imaging. Moreover, assessing fine fiber structures, such as the superior cerebellar peduncle, benefits from ultra-high field MRI due to the higher resolution and higher contrast-to-noise ratios achievable, thereby minimizing partial volume effects and facilitating better structural delineation.

METHODS

The study was conducted in accordance with the Declaration of Helsinki. Institutional review board approval was obtained and all subjects provided written informed consent. Eight Friedreich’s ataxia patients (mean age 38 ± 15 years; four female) and six healthy controls (mean age 46 ± 16 years; four female) were scanned on a 7 T whole-body MR system (Magnetom 7 T, Siemens Healthcare, Germany) with a 8Tx/32Rx-channel head coil (Nova Medical Inc., Wakefield, MA, USA) driven in CP+ mode by use of an in-house-constructed Butler matrix. The following sequences were acquired: a monopolar 3D gradient-echo (GRE), a multi-echo turbo spin echo (ME-TSE) with turbo factor 5, a 2D readout segmentation of long variable echo-trains (RESOLVE)4,5 in stimulated echo acquisition mode (STEAM)6,7 with two diffusion weightings (b = 50 s/mm2, b = 800 s/mm2) and 20 diffusion directions, a MP2RAGE with inversion times of 900 ms and 2750 ms, and a pre-saturation‐based 2D turbo flash for B1 mapping. All other sequence parameters are shown in Table 1.

For susceptibility map generation, phase data were combined on the scanner using ASPIRE8, and brain masks were generated from the first echo of the magnitude images using FSL-BET9. Phase images were unwrapped using Laplacian-based phase unwrapping10-12, and the background field was removed with V-SHARP11,12 with kernel size up to 12 mm. Susceptibility maps were calculated in Matlab (R2017b, MathWorks, Natick, USA) using the STAR-QSM algorithm13. Susceptibility maps were referenced to cerebrospinal fluid in the atrium of the lateral ventricles.

T2 maps were generated form the ME-TSE data and the B1 map using a dictionary-based method14. For T1 mapping and diffusion fractional anisotropy, vendor-provided maps were used.

Volumes of interest (VOIs) (see Figure 1) in the superior cerebellar peduncle were manually drawn on each contrast using the Medical Imaging Interaction Toolkit (MITK)15,16. Differences observed for susceptibility values, diffusion fractional anisotropy, and T2 and T1 values were assessed using a two sample t-test in Matlab. A p-value of less than 0.05 was considered statistically significant.

RESULTS

Figure 2 shows box plots of susceptibility values, diffusion fractional anisotropy values, and T2 and T1 values of the superior cerebellar peduncle in Friedreich’s ataxia patients and healthy controls. The SCP had a median susceptibility of −0.023 ppm for patients and −0.043 ppm for controls, median diffusion fractional anisotropy of 0.71/ 0.85 for patients/ controls, median T2 values of 60/ 72 ms for patients/ controls, and median T1 values of 1382/ 1289 ms for patients/ controls. For diffusion anisotropy (p=0.0003) and for T2 values (p=0.005) the differences between healthy controls and patients were statistically significant; for susceptibility values (p=0.067) and T1 values (p=0.160) the differences were not statistically significant.

In Figure 3, representative slices of susceptibility maps, color-coded diffusion fractional anisotropy maps, and T2 and T1 maps of one healthy control and one patient of the same age and same sex are shown. An atrophy of the superior cerebellar peduncles can be observed in all patient images (second column). In QSM and in diffusion images, SCP (arrow heads) can be clearly depicted in the healthy control showing more diamagnetic susceptibility and higher fractional anisotropy than in the patient. In T2 maps, higher values can be observed in the heathy control than in the patient as well as lower T1 values in T1 maps.

DISCUSSION AND CONCLUSION

MRI can not only visualize the degeneration of the superior cerebellar peduncle in Friedreich’s ataxia but can also quantitatively assess its degeneration. In this ongoing study, already at a rather early stage with a relatively small number of participants, diffusion fractional anisotropy and T2 values were statistically significantly different between Friedreich’s ataxia patients and healthy controls. In future, these methods could become reliable biomarkers for the assessment of disease stage in Friedreich’s ataxia, for example in the evaluation of therapy efficiency.

Acknowledgements

The provision of the ASPIRE gradient echo sequence and corresponding ICE program for coil combination of the 7 T GRE data by Korbinian Eckstein and Simon D. Robinson is kindly acknowledged.

References

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Figures

Figure 1: Volume of interest drawn for the superior cerebellar peduncle on the second echo of the GRE sequence in a healthy volunteer is shown in axial, sagittal and coronal view.

Figure 2: Box plots of mean susceptibility values (a) and mean diffusion fractional anisotropy (b), mean T2 (c) and mean T1 values (d) for all patients and healthy controls. Differences between patients and healthy controls were statistically significant (*) for diffusion fractional anisotropy and T2 values. The whiskers represent the 9th and the 91st percentile.

Figure 3: Representative axial slices of susceptibility maps (QSM), color-coded diffusion fractional anisotropy maps (DW-cFA), T2, and T1 maps depicting the superior cerebellar peduncle (arrow heads) in one healthy control (first column) and one patient (second column).

Table 1: Measurement parameters of the multi-echo gradient echo, the ME-TSE, the RESOLVE, the MR2RAGE, and the turbo flash sequences.

Proc. Intl. Soc. Mag. Reson. Med. 27 (2019)
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