RT Journal Article
SR Electronic
T1 Quantitation of brain tumour microstructure response to Temozolomide therapy using non-invasive VERDICT MRI
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 182675
DO 10.1101/182675
A1 Tom A. Roberts
A1 Harpreet Hyare
A1 Giulia Agliardi
A1 Ben Hipwell
A1 Angela d’Esposito
A1 Andrada Ianus
A1 James O. Breen-Norris
A1 Rajiv Ramasawmy
A1 Valerie Taylor
A1 David Atkinson
A1 Shonit Punwani
A1 Mark F. Lythgoe
A1 Bernard Siow
A1 Sebastian Brandner
A1 Jeremy Rees
A1 Eleftheria Panagiotaki
A1 Daniel C. Alexander
A1 Simon Walker-Samuel
YR 2017
UL http://biorxiv.org/content/early/2017/08/30/182675.abstract
AB There has been slow progress in the development of new therapeutic strategies for treating brain tumours, partly because assessment of treatment response is difficult and largely reliant on simple bi-dimensional measurements of MRI contrast-enhancing regions. Hence, there is a clinical need to develop improved imaging techniques for monitoring treatment response. In this study, we evaluate VERDICT (Vascular, Extracellular and Restricted Diffusion for Cytometry in Tumors) MRI in mouse glioblastomas for the quantification of tumour microstructure and assessment of response to Temozolomide (TMZ) chemotherapy, and, we investigate the feasibility of applying VERDICT MRI in a range of human gliomas. VERDICT MRI detected response to TMZ earlier than structural and apparent diffusion coefficient (ADC) measurements. A significant reduction in the cell radius parameter was detected three days earlier than ADC and six days earlier than structural MRI. Histological analysis showed the same trend as VERDICT of decreased intracellular volume fraction in the TMZ-treated mice. Vascular volume fraction was not altered by TMZ, which was consistent with optical projection tomography measurements. In patients, glioblastoma compartmental volume fractions showed good agreement with mouse glioblastoma parameters. The VERDICT parameters varied across the human gliomas, with raised intracellular volume fraction in the oligodendrogliomas and elevated cell radius in both low-grade tumours subtypes. In conclusion, our results suggest that VERDICT MRI is more sensitive at detecting TMZ response than structural or ADC measurements. In patients, VERDICT is feasible within clinical scan times, and performed best at characterising glioblastoma. Further optimisation should improve assessment of different glioma subtypes.