Abstract

PurposeTo develop a statistical method of combining multimodal MRI (mMRI) of adult glial brain tumours to generate tissue heterogeneity maps that indicate tumour grade and infiltration margins.Materials and methodsWe performed a retrospective analysis of mMRI from patients with histological diagnosis of glioma (n = 25). 1H Magnetic Resonance Spectroscopic Imaging (MRSI) was used to label regions of “pure” low- or high-grade tumour across image types. Normal brain and oedema characteristics were defined from healthy controls (n = 10) and brain metastasis patients (n = 10) respectively. Probability density distributions (PDD) for each tissue type were extracted from intensity normalised proton density and T2-weighted images, and p and q diffusion maps. Superpixel segmentation and Bayesian inference was used to produce whole-brain tissue-type maps.ResultsTotal lesion volumes derived automatically from tissue-type maps correlated with those from manual delineation (p < 0.001, r = 0.87). Large high-grade volumes were determined in all grade III & IV (n = 16) tumours, in grade II gemistocytic rich astrocytomas (n = 3) and one astrocytoma with a histological diagnosis of grade II. For patients with known outcome (n = 20), patients with survival time < 2 years (3 grade II, 2 grade III and 10 grade IV) had a high-grade volume significantly greater than zero (Wilcoxon signed rank p < 0.0001) and also significantly greater high grade volume than the 5 grade II patients with survival >2 years (Mann Witney p = 0.0001). Regions classified from mMRI as oedema had non-tumour-like 1H MRS characteristics.Conclusions1H MRSI can label tumour tissue types to enable development of a mMRI tissue type mapping algorithm, with potential to aid management of patients with glial tumours.

Highlights

  • Gliomas are the most common primary brain tumour and have heterogeneous patterns of infiltrative growth (Burger et al, 1988)

  • Such generalised radiation margins can result in Abbreviations: tCho, total cholines; tCr, total creatines; CSF, cerebrospinal fluid; FLAIR, fluid attenuated inversion recovery; GII, grade II; GIII, grade III; GIV, grade IV; Glx, glutamate & glutamine; GM, grey matter; MET, metastasis; mMRI, multimodal MRI; MRS, magnetic resonance spectroscopy; Magnetic Resonance Spectroscopic Imaging (MRSI), magnetic resonance spectroscopic imaging; NAA, N-acetyl aspartate; necrotic tissue (Ne), necrosis; Probability density distributions (PDD), probability density distribution; PDw, proton density weighted; PDn, proton density normalised; PRESS, point resolved spectroscopy; RGB, red green blue; ROI, region of interest; T2w, T2 weighted; T2n, T2 normalised; VO, vasogenic oedema; white matter (WM), White matter

  • 35 brain tumour patients with histopathological diagnosis were studied retrospectively: WHO grade II (5 diffuse astrocytomas, 3 gemistocytic rich astrocytomas, 1 oligoastrocytoma); WHO grade III (3 anaplastic astrocytoma, 1 anaplastic oligoastrocytoma); WHO grade IV (11 glioblastomas, 1 gliosarcoma); and 10 brain metastases (MET). (Note: these subtypes reflect histopathological terminology at the time of original diagnosis, whereas in the current WHO 2016 classification (Louis et al, 2016), what may have been defined as oligoastrocytoma is defined as either astrocytoma or oligodendroglioma according to 1p19q status)

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Summary

Introduction

Gliomas are the most common primary brain tumour and have heterogeneous patterns of infiltrative growth (Burger et al, 1988). While conventional MRI does indicate likely tumour grade (Lasocki et al, 2015), it fails to determine the extent of tumour infiltration into surrounding normal appearing brain (Yamahara et al, 2010) This is reflected in current radiotherapy treatment guidelines, recommending fixed irradiation margins of 2-3 cm beyond T1-weighted contrast enhancement for high-grade gliomas (Stupp et al, 2009) that aims to irradiate and treat any infiltrative tumour tissue that is present. Such generalised radiation margins can result in Abbreviations: tCho, total cholines; tCr, total creatines; CSF, cerebrospinal fluid; FLAIR, fluid attenuated inversion recovery; GII, grade II; GIII, grade III; GIV, grade IV; Glx, glutamate & glutamine; GM, grey matter; MET, metastasis; mMRI, multimodal MRI; MRS, magnetic resonance spectroscopy; MRSI, magnetic resonance spectroscopic imaging; NAA, N-acetyl aspartate; Ne, necrosis; PDD, probability density distribution; PDw, proton density weighted; PDn, proton density normalised; PRESS, point resolved spectroscopy; RGB, red green blue; ROI, region of interest; T2w, T2 weighted; T2n, T2 normalised; VO, vasogenic oedema; WM, White matter

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