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Title: Investigation of local brain invasion by cerebral metastases and implications for clinical management
Author: Zakaria, R.
ISNI:       0000 0004 6059 0145
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2016
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Brain metastases are common intracranial tumours which cause considerable morbidity and mortality. There are a variety of treatment modalities for brain metastases, including surgery, radiation and chemotherapy. There is, however, disagreement about the best combination of these therapies and prognostic scoring systems are not individualised. MRI is frequently obtained in the course of diagnosing these tumours and advanced MRI sequences, in particular diffusion MRI, which measures white matter disruption, may provide useful prognostic information which is patient and tumour specific. Finally, the interface between the brain metastasis and the surrounding brain has been poorly investigated compared to intrinsic brain tumours such as glioma, and may be a rich source of therapeutic targets and biomarkers. This thesis therefore aimed to derive biological and radiological markers of local brain metastasis invasion, intracranial progression and survival which may be used in clinical practice, whilst deepening scientific understanding of the brain-brain metastasis interface. Expression of the metastasis-inducing protein S100A4 was identified as a possible predictor of metastasis recurrence post operatively and OPN as a possible marker of radiation response. Using diffusion MRI, the change in the change in the apparent diffusion coefficient (ADC) across the brain-brain metastasis boundary was found to be a reliable, repeatable measure on clinically obtained scans and independently associated with overall survival for operated brain metastases. Finally, using combined image-guided neurosurgical samples and diffusion tensor imaging, we have shown that the FA in the peritumoural region is a surrogate marker of the density of T cell infiltration there and that both increased CD3+ T cell infiltration and reduced FA (corresponding to more white matter tract disruption) are associated with prolonged overall survival after macroscopic resection. These studies highlight the importance of studying the brain-brain metastasis interface both radiologically and biologically whilst offering truly novel avenues for further study in the field, including imaging, tissue biomarkers and potential therapeutic targets.
Supervisor: Rudland, Philip ; Jenkinson, Michael ; Sluming, Vanessa Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral