Subsidiary neuro-oncology research centres

Understanding Tumour Heterogeneity in Brain Tumour Patients using Multimodal MR and PET Imaging (Cambridge)

My group uses advanced multimodal MR and PET imaging to understand the heterogeneity of gliomas (high and low grade) in individual patients. We know that gliomas, tumours diagnosed by their appearances on light microscopy, are among the most heterogeneous tumours but still do not have a method of accounting for this heterogeneity. Attempts at using tissue markers are progressing but cannot impact surgically based therapies. Imaging provides a non-invasive method of assessing tumour pathology.

My work focuses on two areas:

  1. Intertumoural heterogeneity (i.e. differences between individuals). I am particularly interested in the heterogeneity of tumour invasion. We know from post-mortem studies there is great variation in tumour invasion with 20-25% of GBM patients having tumour extending less than a centimetre from the edge of the tumour mass, with another 20% extending more than 3 centimetres. My work using methods devised in geomechanics to analyse diffusion tensor MR has been able to identify this invasion on the basis of disruption of white matter tracts. Biopsy studies have confirmed these abnormalities to be tumour and follow up studies suggest it can predict patterns of tumour progression and overall survival for the patient. We are currently using multi-modal MR imaging to study the invasive microenvironment to better define invasive phenotypes and plan to use these methods to determine treatment.

Using these methods has allowed us for the first time to accurately identify the invasive margin in patients and therefore study the biology of these invasive regions with both cell culture work (in conjunction with Colin Watts lab) as well as microdialysis to understand the extracellular peptides (in conjunction with Peter Hutchinson’s lab).

  1. Intratumoural heterogeneity (i.e. differences within a tumour in an individual patient). This is an area where there is much recent interest. I am particularly interested in studying variation of response to chemotherapy/radiotherapy and drug uptake. We are developing [3-N-11C-methyl]-temozolomide a PET tracer that identifies activated temozolomide to study drug delivery in these tumours. We plan to understand the factors that relate to drug uptake and see if regions of poor response are due to poor drug uptake. We hope this work will allow us to predict response of individuals to chemotherapy.

Members of Group

Stephen Price – NIHR Clinician Scientist & Hon. Consultant Neurosurgeon
Owen Thomas – Clinical Lecturer in Radiology
Amy Frary – Research Nurse
Anna Kolb – PhD student (joint supervised with Colin Watts)
Natalie Boonzaier – PhD student (from September 2012)

Contact details

Mr Stephen J Price PhD FRCS(Neuro.Surg)
NIHR Clinician Scientist & Hon. Consultant Neurosurgeon
Neurosurgery Division
Department of Clinical Neurosciences
Box 167, Addenbrooke’s Hospital
Cambridge CB2 0QQ

E-mail: sjp58@cam.ac.uk
Tel.: 01223 274295

References

  1. MA McLean, A Sun, TE Bradstreet, AK Schaeffer, H Liu, R Iannone, G Herman, R A Railkar,  I Joubert, JH Gillard, SJ Price and JR Griffiths (2011) Repeatability of edited lactate and other metabolites in astrocytoma at 3 Tesla. Journal of Magnetic Resonance Imaging [Epub ahead of print, 25 April 2012].
  2. SJ Price, IR Whittle, K Ashkan, P Grundy & G Cruickshank (2012) NICE Guidance on the Use of Carmustine Wafers in High Grade Gliomas: A National Study on Variation in Practice. British Journal of Neurosurgery – [Epub ahead of print 6 April 2012]
  3. R Ryan, S Booth and S Price(2012) Corticosteroid-use in primary and secondary brain tumour patients: a review. Journal of Neuro-Oncology 106:449-459.
  4. SJ Price and JH Gillard (2012) Imaging biomarkers of brain tumour margin and tumour invasion. The British Journal of Radiology 84 (Suppl. 2): S159-S167.
  5. SJ Price, DJ Tozer and JH Gillard (2012) Methodology of Diffusion-Weighted, Diffusion Tensor and Magnetisation Transfer Imaging. The British Journal of Radiology 84 (Suppl. 2): S121-S126.
  6. MR Guilfoyle, RA Weerakkody, A Oswal, I Oberg, C Jeffery, K Haynes, PJ Kullar, D Greenberg, SJ Jefferies, F Harris, SJ Price, S Thomson, and C Watts (2011) Implementation of neuro-oncology service reconfiguration in accordance with NICE guidance provides enhanced clinical care for patients with glioblastoma multiforme. British Journal of Cancer 104:1810-1815.
  7. SJ Price, HA Green, AF Dean, J Joseph, PJ Hutchinson, and JH Gillard (2011) Correlation of MR Relative Cerebral Blood Volume Measurements with Cellular Density and Proliferation in High-Grade Gliomas: An Image-Guided Biopsy Study. AJNR American Journal of Neuroradiology 32(3):501-506.
  8. S-A Price, SJ Price and P Whitfield (2011) Low-grade Gliomas. Advances in Clinical Neuroscience and Rehabilitation 11(1):24-30.
  9. SJ Price (2010) Advances in imaging low-grade gliomas. Advances and Technical Standards in Neurosurgery 35:1-34.
  10. HJ Marcus, KL Carpenter, SJ Price, and PJ Hutchinson (2010) In vivo assessment of high-grade glioma biochemistry using microdialysis: a study of energy-related molecules, growth factors and cytokines. Journal of Neuro-oncology 97:11-23.
  11. SJ Price, TD Fryer, MC Cleij, AF Dean, J Joseph, R Salvador, DD Wang, PJ Hutchinson, JC Clark, NG Burnet, JD Pickard, FI Aigbirhio, and JH Gillard (2009) Imaging regional variation of cellular proliferation in gliomas using 3′-deoxy-3′-[18F]fluorothymidine positron-emission tomography: an image-guided biopsy study. Clinical Radiology 64:52-63.
  12. AD Waldman, A Jackson, SJ Price, CA Clark, TC Booth, DP Auer, PS Tofts, DJ Collins, MO Leach, and JH Rees (2009) Quantitative imaging biomarkers in neuro-oncology. Nat Rev Clin Oncol 6:445-454.
  13. SJ Price (2007) The role of advanced MR imaging in understanding brain tumour pathology. Br.J Neurosurg. 21:562-575.
  14. NG Burnet, AG Lynch, SJ Jefferies, SJ Price, PH Jones, NM Antoun, JH Xuereb, and U Pohl (2007) High grade glioma: imaging combined with pathological grade defines management and predicts prognosis. Radiother.Oncol 85:371-378.
  15. MR Guilfoyle, H Fernandes, and SJ Price (2007) In vivo alteration of Strata valve setting by vagus nerve stimulator-activating magnet. British Journal of Neurosurgery 21:41-42.
  16. SJ Price, R Jena, NG Burnet, TA Carpenter, JD Pickard, and JH Gillard (2007) Predicting patterns of glioma recurrence using diffusion tensor imaging. European Radiology 17:1675-1684.
  17. SJ Price, R Jena, HA Green, NF Kirkby, AG Lynch, CE Coles, JD Pickard, JH Gillard, and NG Burnet (2007) Early Radiotherapy Dose Response and Lack of Hypersensitivity Effect in Normal Brain Tissue: a Sequential Dynamic Susceptibility Imaging Study of Cerebral Perfusion. Clinical Oncology 19:577-587.
  18. A Pena, HAL Green, TA Carpenter, SJ Price, JD Pickard, and JH Gillard (2006) Enhanced visualization and quantification of magnetic resonance diffusion tensor imaging using the p:q tensor decomposition. The British Journal of Radiology 79:101-109.
  19. SJ Price, R Jena, NG Burnet, PJ Hutchinson, AF Dean, A Pena, JD Pickard, TA Carpenter, and JH Gillard (2006) Improved Delineation of Glioma Margins and Regions of Infiltration with the Use of Diffusion Tensor Imaging: An Image-Guided Biopsy Study. American Journal of Neuroradiology 27:1969-1974.
  20. R Jena, SJ Price, C Baker, SJ Jefferies, JD Pickard, JH Gillard, and NG Burnet (2005) Diffusion tensor imaging: possible implications for radiotherapy treatment planning of patients with high-grade glioma . Clinical Oncology 17:581-590.
  21. SJ Price, A Pena, NG Burnet, R Jena, HA Green, TA Carpenter, JD Pickard, and JH Gillard (2004) Tissue signature characterisation of diffusion tensor abnormalities in cerebral gliomas. Eur.Radiol 14:1909-1917.
  22. SJ Price, A Pena, NG Burnet, JD Pickard, and JH Gillard (2004) Detecting glioma invasion of the corpus callosum using diffusion tensor imaging. British Journal of Neurosurgery 18:391-395.
  23. SJ Price, NG Burnet, T Donovan, HA Green, A Pena, NM Antoun, JD Pickard, TA Carpenter, and JH Gillard (2003) Diffusion Tensor Imaging of Brain Tumours at 3T: A Potential Tool for Assessing White Matter Tract Invasion? Clin.Radiol 58:455-462.


Neuro-oncology research – Exeter

In Exeter our research focuses on factors that lead to the establishment of brain metastasis, with a view to trying to prevent this process from occurring. Our work is primarily cell based and looks at the interaction of human tumour cells, microvascular endothelial cells and astrocytes. Currently the focus is on understanding factors that influence the attachment of lung tumour cells to the brain endothelium.

Drs N.J.Gutowski N.J.Gutowski@exeter.ac.uk and J.L.Whatmore J.L.Whatmore@exeter.ac.uk