Tractography delineates microstructural changes in the trigeminal nerve after focal radiosurgery for trigeminal neuralgia

Mojgan Hodaie, David Qixiang Chen, Jessica Quan, Normand Laperriere, Mojgan Hodaie, David Qixiang Chen, Jessica Quan, Normand Laperriere

Abstract

Purpose: Focal radiosurgery is a common treatment modality for trigeminal neuralgia (TN), a neuropathic facial pain condition. Assessment of treatment effectiveness is primarily clinical, given the paucity of investigational tools to assess trigeminal nerve changes. Since diffusion tensor imaging (DTI) provides information on white matter microstructure, we explored the feasibility of trigeminal nerve tractography and assessment of DTI parameters to study microstructural changes after treatment. We hypothesized that trigeminal tractography provides more information than 2D-MR imaging, allowing detection of unique, focal changes in the target area after radiosurgery. Changes in specific diffusivities may provide insight into the mechanism of action of radiosurgery on the trigeminal nerve.

Methods and materials: Five TN patients (4 females, 1 male, average age 67 years) treated with Gamma Knife radiosurgery, 80 Gy/100% isodose line underwent 3Tesla MR trigeminal nerve tractography before and sequentially up to fourteen months after treatment. Fractional anisotropy (FA), radial (RD) and axial (AD) diffusivities were calculated for the radiosurgical target area defined as the region-of-interest. Areas outside target and the contralateral nerve served as controls.

Results: Trigeminal tractography accurately detected the radiosurgical target. Radiosurgery resulted in 47% drop in FA values at the target with no significant change in FA outside the target, demonstrating highly focal changes after treatment. RD but not AD changed markedly, suggesting that radiosurgery primarily affects myelin. Tractography was more sensitive than conventional gadolinium-enhanced post-treatment MR, since FA changes were detected regardless of trigeminal nerve enhancement. In subjects with long term follow-up, recovery of FA/RD correlated with pain recurrence.

Conclusions: DTI parameters accurately detect the effects of focal radiosurgery on the trigeminal nerve, serving as an in vivo imaging tool to study TN. This study is a proof of principle for further assessment of DTI parameters to understand the pathophysiology of TN and treatment effects.

Conflict of interest statement

Competing Interests: The authors have read the journal's policy and have the following conflicts. MH is the surgical co-director of the Gamma Knife radiosurgery unit at the Toronto Western Hospital. DQC, JQ and NL have no conflicts to report. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1. Baseline MR imaging, tractography of…
Figure 1. Baseline MR imaging, tractography of the trigeminal nerve, target and ROI definition.
Image processing commenced with baseline anatomical 3TMR images (A, axial section, midpontine level). Diffusion tensor images with overlaid colour-by-orientation fibers are shown in B. Reconstructed tracts of the trigeminal nerve onto colour-by-orientation images are shown in C. Panel D depicts the contour of the trigeminal nerve (blue) and location of the radiosurgical shot. Yellow circle denotes the 80% isodose line, representing the “target” of Gamma radiation to the nerve. Panel E shows focal area of post-gadolinium enhancement on the trigeminal nerve (yellow arrowhead), defining the “target” ROI. Panel F shows the location of the “proximal” ROI, proximal to the area of gadolinium enhancement (B, white arrow), and “unaffected” ROI, contralateral nerve.
Figure 2. Target ROI is characterized by…
Figure 2. Target ROI is characterized by focal diffusivity changes.
Comparison of diffusivities change across all ROIs reveal statistically significant decrease in FA and rise in RD in “target” post-radiosurgery treatment. Rise in RD and non-significant changes in AD point to changes in myelination as main contributor of diffusivity changes. (*denotes statistically significant changes, FA p = 0.027, RD p = 0.002; two-tailed t-test. NS = no statistical significance. RD,AD scalar values are multiplied ×1000 for ease of representation).
Figure 3. Changes in FA after GKRS…
Figure 3. Changes in FA after GKRS treatment are dynamic.
Sequential images for subject S1 are shown at 0, 1, 7 and 14 months after Gamma Knife radiosurgery (GKRS) treatment. Top panel depicts serial MR images, showing similar gadolinium enhancement in the midcisternal portion of the nerve after treatment with time (yellow triangles). Middle panel shows reconstructed trigeminal nerve tracts for the same time points. At one month, marked FA decrease is seen in the target area (high FA pre-treatment, blue now appearing as low FA, orange) and tract-pruning due to fall-off of FA value. At 14 months the FA values trends towards baseline, with a longer reconstructed trigeminal segment. The area of low FA has also resolved. Lower panel shows a graph of the scalar values of FA with time. At 14 months, subject S1 has experienced full recurrence of her pain.
Figure 4. Tractography outlines detailed FA changes…
Figure 4. Tractography outlines detailed FA changes in the trigeminal nerve after GKRS treatment.
Panels A–D depict the trigeminal nerve tracts pre and post-treatment for subjects S1(A,B) and S2 (C,D). The area between the yellow and blue arrows delineates the cisternal segment, with the yellow arrow being proximal to the brainstem and the blue arrow distal. The red arrow denotes the target area, which corresponds to the region where the greatest change in FA was observed. In S1, FA change affects primarily the outlying fibers of the nerve, while for S2, FA changes are seen in the inferior portion of the cisternal segment of the trigeminal nerve.
Figure 5. Tractography can detect changes in…
Figure 5. Tractography can detect changes in the trigeminal nerve in the absence of post-treatment gadolinium enhancement: Panels A to E delineate FA changes seen after treatment. Subject S2 did not show post-treatment MR gadolinium enhancement.
Panel A shows location of radiosurgical target during treatment planning. Panels B, C depict post-treatment MR and lack of gadolinium-enhancement (yellow arrowhead). Reconstructed trigeminal tracts are shown in panel D (pre-treatment) and E (post-treatment), with clear FA changes in the target area (blue arrowhead).

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