Heterogeneity in brain metastases – advanced MRI at the brain-tumour interface predicts aggressive growth patterns.

Background Brain metastases are increasingly common tumours treated as a homogenous group with SRS, surgery and whole brain radiotherapy. However, there are significant rates of local recurrence. We prospectively investigated intra- and inter-tumour heterogeneity in a series of brain metastases undergoing advanced MRI followed by image guided neurosurgical sampling from the leading edge in the course of resection. Method Pre-surgery 3T-MRI was obtained using 32 direction DTI and T1 with gadolinium. Image guided sampling was performed at the leading edge of the tumour as it was removed with reference samples from the core. Histogram analysis of regions of interest were matched to tissue locations. Growth pattern was assessed by a pathologist using a previously described classification and CD34, Ki67, necrosis and cellularity were scored semi-automatically using NIH ImageJ software. Survival and brain recurrence were recorded. Results Twenty-six cases were included. The mean diffusivity (MD) values recorded at the edge of metastases were significantly different in distribution, median and mean from those at the core (Wilcoxon matched pairs, p=.001). There was significantly higher necrosis (p=.026) and a trend to higher CD34 density at the leading edge versus the core. MD and the change in MD across the leading edge correlated with cellularity (r=-.41, p=.047) but did not predict clinical outcomes nor pathological growth pattern. Metastases which appeared more diffusely invasive pathologically had a significantly lower peritumoral fractional anisotropy (FA) (p=.039) suggesting more tract white matter disruption. These tumours also had more dense CD34 staining (r=-.55, p=.041) at their leading edge and a trend to lower survival and more rapid intracranial recurrence. Conclusion There is significant intra-tumoral heterogeneity among brain metastases and assessment of the brain-tumour interface radiologically and biologically may yield more useful information about behaviour and prognosis than assessing the whole metastasis