The use of quantitative susceptibility imaging for the evaluation of acute MS lesion formation
Vanessa Wiggermann1,2, Enedino Hernandez-Torres2,3, Inga C Ibs4, Stephanie M Schoerner5, Galina Vorobeychik6, Luanne Metz7, David KB Li8,9, Anthony Traboulsee9,10, and Alexander Rauscher2,9,11

1Physics and Astronomy, University of British Columbia, Vancouver, BC, Canada, 2Pediatrics, University of British Columbia, Vancouver, BC, Canada, 3UBC MRI Research Centre, University of British Columbia, Vancouver, BC, Canada, 4University of Osnabrueck, Osnabrueck, Germany, 5Technical University of Dortmund, Dortmund, Germany, 6Fraser Health MS Clinic, Burnaby, BC, Canada, 7Clinical Neurosciences, University of Calgary, Calgary, AB, Canada, 8Radiology, University of British Columbia, Vancouver, BC, Canada, 9Center for Brain Health, University of British Columbia, Vancouver, BC, Canada, 10Medicine (Neurology), University of British Columbia, Vancouver, BC, Canada, 11Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada

Synopsis

Using magnetic-susceptibility based MR techniques for the assessment of damage due to multiple sclerosis (MS) has been controversial, in particular in MS lesions where the underlying pathological changes are not yet fully understood. Here, we investigated the changes of the MR frequency and quantitative susceptibility signal during acute MS lesion formation. We observed that both metrics behave similarly, indicating that non-local effects have little contribution to the QSM signal increase and hence dipole inversion might not be required to assess damage during MS lesion formation accurately.

Purpose

Quantitative susceptibility mapping (QSM) has become an exciting new research field in the past 10 years and is starting to be applied for every day clinical purposes such as the detection of vessels1, differentiation of calcium and iron clusters2, and more recently for the assessment of iron accumulation in the brain3 or other body parts4. The quantitative assessment of damage in neurodegenerative diseases is also gaining momentum, however in particular the characterization of damage in multiple sclerosis (MS) lesions has been controversial. Studies utilizing frequency shift (FS) imaging demonstrated a steep signal increase at the time of MS lesion formation, attributed to microstructural changes during to the transition of healthy myelin into myelin debris5,6. Similarly, in a cross-sectional study QSM detected susceptibility changes over time, attributing increases in QSM signal at time of lesion formation to iron accumulation7. Given the non-locality of the underlying MR phase signal, one may argue for the necessity of performing QSM. However, if the initial FS increase is not due to bulk magnetic susceptibility changes, but due to structural changes alone, no non-local field changes will be created and therefore QSM and FS maps will provide the same information. Here, we tested these hypotheses by comparing the MR FS and QSM values during the formation of new acute MS lesions.

Methods

In a randomized, placebo controlled, double-blind trial of Minocycline, 3T MRI was performed for 38 patients with clinically isolated syndrome at month 0,3,6,12 and 24, if the patients had not convert to McDonald definite MS. MR FS maps and QSM maps were calculated on all time points from the same gradient-echo acquisition (5 echoes, TR/TE/ΔTE=48/20/6ms, acq. voxelsize=0.6x0.8x2.4 mm3, reconstructed to 0.4x0.4x1.2 mm3). The data was unwrapped using a Laplacian approach8 and weakly high-pass filtered to obtain background field removed FS maps. For QSM, the unwrapped images were background filtered using SHARP9 and susceptibilities were estimated using the superfast dipole inversion9 approach with truncated singular value decomposition and thresholded k-space division at 0.02 and 0.53. We identified enhancing lesions on co-registered Gadolinium(Gd)-enhanced T1-weighted image, and defined their month of appearance as Month 0 on the common time line. All regions of interest were segmented with an in-house developed software and average FS and QSM values were determined for all regions.

Results

9/38 patients had Gd-enhancing lesions on one of the time points. Mapping them onto a common time line allowed us to estimate QSM and FS values at -6,-3,0,3,6,9,12 and 21 months of lesion age in 2,23,32,24,5,12,4 and 3 lesions, respectively. Given the low number of lesions at month -6,12 and 21, we excluded these time points. Comparing the mean FS and QSM values in all Gd-enhancing lesions before and after their appearance (Fig. 1), we observed a significant increase for both metrics between month -3 to month 3 (p<0.004) which remained significantly elevated up to month 9 (p<0.004). FS maps also showed a significant signal elevation already at month 0 (p=0.03), while QSM maps did not reach significance at this time point. Figure 2 qualitatively compares FS (upper row) and QSM (bottom row) for a lesion that appeared at the second time point. The lesion (marked with a red circle) showed the same behaviour on both scans, appearing ring-like at first, followed by a volume reduction, but consistently elevated FS and QSM values.

Discussion

FS and QSM values depend strongly on the chosen signal processing pipeline. Therefore, values may not be comparable between studies. We normalized our FS values to the Larmor frequency at 3T, however the actual Larmor frequency will vary from patient to patient. Similarly, normalization of QSM is not yet standardized10. Due to white matter loss and brain atrophy in MS, we decided not to normalize the susceptibility values potentially causing larger patient-to-patient variations. The low number of lesions at month 6 may further contribute to the lack of significance and inconsistent signal reduction on the FS maps.

Conclusion

We demonstrated in this work that MS lesions appear to show very similar changes on MR frequency and QSM maps, indicating that the dipole inversion may not be necessary due to the apparent lack of bulk magnetic susceptibility changes during early lesion formation.

Acknowledgements

This study was supported by the Multiple Sclerosis Society of Canada.

References

[1] Reichenbach et al., Radiology 204; 1997 [2] Deistung et al., Z Med Phys 16; 2006 [3] Langkammer et al., NeuroImage 62; 2012 [4] Sharma et al., Magn Res Med 74; 2014 [5] Wiggermann et al., Neurology 81; 2013 [6] Yablonskiy et al., PNAS 109; 2012 [7] Chen et al., Radiology 271; 2014 [8] Li et al., NeuroImage 55; 2011 [9] Schweser et al., Magn Res Med 69; 2013 [10] Acosta-Cabronero et al., PLOS One 8; 2013

Figures

Mean and standard errors for FS (upper row) and QSM (bottom row) maps across 32 lesions. The numbers in between the 2 graphs reflect the number of lesions that provided information at each time point. Month 6 in particular has only 5 lesions contributing, which might cause the lack of significance and the inconsistant reduction on FS maps. (** p<0.004, * p=0.03)

Exemplary visual comparison of FS (upper row) and QSM (bottom row) changes during the time of lesion formation. The lesion enhanced at the second time point and appeared initially ring-like, followed by a more homogeneous appearance and volume loss after 3 and 9 months.



Proc. Intl. Soc. Mag. Reson. Med. 24 (2016)
1551