Detection of early changes in the post-radiosurgery vestibular schwannoma microenvironment using multinuclear MRI

Daniel Lewis,Simon K Lloyd,Ka-Loh Li,Damien J Mchugh,Xiaoping Zhu,Catherine Mcbain,Andrew T King,Alan Jackson,David J Coope,Omar N Pathmanaban

doi:10.1038/s41598-021-95022-6

Abstract

Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The mechanisms of tumour response are, however, unknown and in this study we sought to evaluate changes in the irradiated VS tumour microenvironment through a multinuclear MRI approach. Five patients with growing sporadic VS underwent a multi-timepoint comprehensive MRI protocol, which included diffusion tensor imaging (DTI), dynamic contrast-enhanced (DCE) MRI and a spiral 23Na-MRI acquisition for total sodium concentration (TSC) quantification. Post-treatment voxelwise changes in TSC, DTI metrics and DCE-MRI derived microvascular biomarkers (Ktrans, ve and vp) were evaluated and compared against pre-treatment values. Changes in tumour TSC and microvascular parameters were observable as early as 2 weeks post-treatment, preceding changes in structural imaging. At 6 months post-treatment there were significant voxelwise increases in tumour TSC (p < 0.001) and mean diffusivity (p < 0.001, repeated-measures ANOVA) with marked decreases in tumour microvascular parameters (p < 0.001, repeated-measures ANOVA). This study presents the first in vivo evaluation of alterations in the VS tumour microenvironment following SRS, demonstrating that changes in tumour sodium homeostasis and microvascular parameters can be imaged as early as 2 weeks following treatment. Future studies should seek to investigate these clinically relevant MRI metrics as early biomarkers of SRS response.

Highlights

Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS)
In the present study we show that following radiotherapy, there is an early rise in VS sodium content with > 80% of tumour voxels demonstrating an increase in total sodium concentration (TSC) at 2 weeks post-treatment
Following an early post-treatment rise in some tumours, we demonstrate that at 6 months post radiotherapy there is a marked decrease in the dynamic contrast-enhanced (DCE)-MRI derived microvascular parameters v p, Ktrans and v e

Summary

Introduction

Stereotactic radiosurgery (SRS) is an established, effective therapy against vestibular schwannoma (VS). The inability to differentiate between these two radically different responses to treatment means that cases of treatment failure are not recognized until after 3 years of continued growth, with the consequent surgical challenges of dealing with what is likely to be a significantly larger tumour with potential radiotherapy induced adherence to the adjacent cranial nerves and brain s tem[8,10]. Fundamental to these clinical challenges is our incomplete understanding of how and why these tumours respond to radiotherapy in the way they do[11,12]. To better predict and monitor treatment responses in VS following SRS we, need a greater understanding of how the microenvironment in these tumours changes following treatment

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