Personalized biomechanical tongue models based on diffusion-weighted MRI and validated using optical tracking of range of motion.

For advanced tongue cancer, the choice between surgery and organ-sparing treatment is often dependent on the expected loss of tongue functionality after treatment. Biomechanical models might assist in this choice by simulating the post-treatment function loss. However, this function loss varies between patients and should, therefore, be predicted for each patient individually. In the present study, the goal was to better predict the postoperative range of motion (ROM) of the tongue by personalizing biomechanical models using diffusion-weighted MRI and constrained spherical deconvolution reconstructions of tongue muscle architecture. Diffusion-weighted MRI scans of ten healthy volunteers were obtained to reconstruct their tongue musculature, which were subsequently registered to a previously described population average or atlas. Using the displacement fields obtained from the registration, the segmented muscle fiber tracks from the atlas were morphed back to create personalized muscle fiber tracks. Finite element models were created from the fiber tracks of the atlas and those of the individual tongues. Via inverse simulation of a protruding, downward, left and right movement, the ROM of the tongue was predicted. This prediction was compared to the ROM measured with a 3D camera. It was demonstrated that biomechanical models with personalized muscles bundles are better in approaching the measured ROM than a generic model. However, to achieve this result a correction factor was needed to compensate for the small magnitude of motion of the model. Future versions of these models may have the potential to improve the estimation of function loss after treatment for advanced tongue cancer.

Recurrent oropharyngeal cancer after organ preserving treatment: pattern of failure and survival.

The objectives is to thoroughly analyze the pattern of failure and oncologic outcome in recurrent oropharyngeal cancer (OPC) after (chemo)radiotherapy and correlate the site of failure to the planned radiation dose. Between January 2010 and April 2014, 57 patients with recurrent OPC after (chemo)radiotherapy were analyzed. Endpoints were pattern of failure and overall survival (OS). Local (LF) and regional failure (RF) were classified as in-field [>50% within gross tumor volume (GTV)], marginal [<50% within GTV but >50% within clinical target volume (CTV)], or out-of-field (>50% outside CTV) recurrences. In the whole group, 70 recurrences were reported. Of the 31 LF, 29 (93.5%) were in-field and 2 (6.5%) were marginal. No out-field LF was reported. Of the 21 RF, 13 RF (62%) were in-field, 6 (28.5%) marginal, and 2 (9.5%) out-of-field recurrences. Forty-three percent of RF was developed in an electively treated neck level, and 2 of them were contralateral. OS at 2 years in recurrent HPV positive, compared to HPV-negative OPC, were 66 and 18%, respectively (p = 0.011). OS was also significantly better in patients that were salvage treatment which was possible (70 vs. 6%, p < 0.001). Median survival after distant failure was 3.6 months. The great majority of LFs were located within the GTV and 43% of RFs developed in an electively treated neck level. The currently used margins and dose recipe and the indication for bilateral nodal irradiation need to be reevaluated. OS was significantly better in recurrent HPV-positive OPC and in patients, where salvage treatment was possible.

Growth-associated protein 43 in lesions and cerebrospinal fluid in multiple sclerosis.

Axonal damage in multiple sclerosis (MS) is correlated to disease progression. Early axonal damage may be compensated for by regenerative processes. Growth-associated protein 43 (GAP-43) is a marker for axonal growth and synaptogenesis in various neurodegenerative diseases. We investigated the expression of GAP-43 in 48 MS grey and white matter lesions of different stages. Decreased GAP-43 expression was found in 74% of the white matter lesions, independent of the lesion stage. In 19 out of 35 white matter lesions, areas of increased GAP-43 expression were present immediately adjacent to the lesions. Increased or unaltered expression was observed in remyelinated lesions. GAP-43 was expressed in neurofilament-positive structures. GAP-43 expression appeared unchanged in grey matter lesions. Macrophages were present in the areas of changed GAP-43 expression. cerebrospinal fluid GAP-43 levels were negatively correlated with magnetic resonance imaging measures of whole-brain atrophy (r = -0.30). In conclusion, these results indicate that decreased GAP-43 immunopositivity reflects axonal damage in MS lesions, which may again be reflected in decreased cerebrospinal fluid levels. The increased levels of GAP-43 in remyelinated or nondemyelinated white matter close to MS lesions may reflect regenerative attempts by damaged axons.