Apparent Diffusion Coefficient Measures on MR Correlate with Survival in Glioblastoma Multiforme

Introduction: Malignant gliomas are currently evaluated by subjective assessment of T2and contrast-enhanced T1-weighted imaging. Glioblastoma multiforme (GBM) is largely considered a single clinical entity for the purposes of treatment rationalisation, although genetic biomarkers which predict response to treatment in glioma from biopsy samples have been discovered. Non-invasive imaging biomarkers which predict glioma behaviour are currently being sought. A glioma edge characteristic, the tumour border sharpness coefficient (TBSC) as described on anatomical MR imaging, has been shown to correlate with 1p/19q status – and therefore with chemosensitivity – in oligodendroglial tumours[1, 2]. Diffusion-weighted imaging exploits the movement of free water molecules and has been described as an indirect proxy of tumour cellular density, tumour infiltration and of tumour extracellular matrix properties[3, 4]. Areas of low diffusion-weighted signal intensity have a high apparent diffusion coefficient (ADC) and vice versa. ADC has been used to differentiate tumour from peri-tumoural oedema and normal brain, and to differentially diagnose enhancing intracranial lesions[5]. In perienhancing regions of glioma with abnormal MR signal, ADC has also been found to be high in oedema, low in tumour, and intermediate in mixed tumour/oedema[6]. The TBSC approach has recently been combined with diffusion-weighted imaging to determine the ADC Transition Coefficient (ATC) which is the rate of change of ADC per unit length across the tumour boundary[7]. The work presented here aimed to compare the ATC with survival data in glioblastoma multiforme (GBM) treated by standard postoperative temozolomide (TMZ) chemoradiotherapy. Since ADC may correlate inversely with cellular density and directly with infiltration, it was hypothesised that tumours exhibiting broader zones of ADC transition between tissues would have more diffuse boundaries, which may represent more infiltrative phenotypes with potentially shorter overall survival. In addition to the ATC at the oedema boundary described previously by Jenkinson et al.(referred to here as ATCO), we proposed the ATC at the tumour boundary (ATCT) to additionally reflect invasiveness and cellularity of the advancing solid tumour front.