research reports

University of Hull

2002/3

Centre for Magnetic Resonance Investigations
Scientific Director: Professor L W Turnbull

Breast Cancer Programme
Mr P. Kneeshaw, Dr M. Lowry, Dr P. Gibbs, Dr D. Manton, Ms C. Tan, Prof L. Turnbull

The breast cancer research portfolio incorporates conventional imaging, single voxel and chemical shift spectroscopic imaging and clinical evaluation of therapeutic impact. Neoadjuvant chemotherapy for locally advanced breast cancer is used with increasing frequency to facilitate conserving surgery and improve prognosis. However there is a pressing need for early evaluation, as detection of poor or failed response would allow second line treatment to be instigated promptly. The role of DCE-MRI, proton MRS and estimation of water ADC is being evaluated against overall tumour volume response, markers of apoptosis (p53, Bcl and Caspase) and surgical findings. The most appropriate timing of these investigations in relation to commencement of therapy is under investigation. Determination of tumour presence, extent and response to treatment for appropriate and cost effective patient management is in progress and forms the basis of a Hull based multi-centre study examining use of MR imaging in patients scheduled for wide local excision. Classification of breast masses and determination of tumour extent are important for cost effective and improved quality of life patient management and work is ongoing in DCIS, invasive ductal and lobular carcinomas (ILC). All breast examinations rely on fast, user friendly, automated analysis of the signal intensity time changes generated during dynamic contrast-enhanced imaging. Work continues in the advancement of models that reflect patho-physiological processes, on the development and implementation of chemical shift spectroscopic imaging and on the accurate and reproducible measurement of T2* relaxation times from which tissue oxygenation can be inferred.

Radiotherapy Planning Research Programme
Dr G. Liney, Dr P. Gibbs, Mr R. Garcia-Alvarez, Prof L. Turnbull

The introduction of inversely planned intensity modulated radiotherapy that allows accurate sculpting of the dose distribution and target-within-target boost dose escalation, relies on imaging techniques for tumour localization. Work is ongoing to amalgamate CT and MR images allowing electron density, detailed anatomical information, metabolite concentrations, tumour vascularity, apparent diffusion coefficient of water, and functional imaging (to determine brain activation) to be incorporated in to the radiotherapy planning process. Studies continue on: the differentiation of benign from malignant disease, using dynamic contrast-enhanced MRI which incorporates arterial input function allowing estimation of blood volume and tissue perfusion; the use of tetrahedral, trace and anisotropic diffusion imaging to examine the apparent diffusion coefficient of contained water; development of reproducible paradigms for functional imaging and incorporation of 3D chemical shift spectroscopic imaging information. These studies are on going in head and neck and prostatic malignancies.

Precise, reproducible, 3D quality assurance of radiotherapy planning prescriptions is paramount to good patient management. Conventional methods of dose verification obtained by plain films, ionization chambers and portal imaging prove inadequate with IMRT and we are currently using MAGIC gels analysed by MRI to provide a method of quantifying complex 3D dose distributions at high spatial resolution. A stable gel composition with a linear response between radiation dose and the MR relaxation rate constant R2 (where R2 = 1/T2) has been developed, and these data have been used to obtain a preliminary verification of realistic radiotherapy plans. Initial results demonstrate dose quantification to within 10% of the delivered intent and accurate 3D representation of the delivered dose with no evidence of geometric distortion.

Gynaecological Research Programme
Prof L. Turnbull, Dr M. Lowry

With the alteration in the pattern of patient referral for gynaecological malignancies, it is an opportune time to evaluate the accuracy of diagnosis and staging of ovarian malignancies. MR-determined tumour stage has been compared with the operative and pathological findings in patients undergoing debulking surgery for primary ovarian malignancy. Initial results which encompass a three year time period show good agreement in findings, with the exception of under-staging of some FIGO stage IC disease, due to failure to appreciate microscopically apparent capsular penetration. Research has concentrated on the diagnostic accuracy of conventional MR imaging, combined with DCE-MRI and evaluation of uptake characteristics leading to highly significance differences between benign and malignant lesions. Work is currently ongoing to compare MR staging accuracy, with respect to surgical findings and potential alteration in patient management, as well as correlation of pharmacokinetic parameters with response to first line cytotoxic chemotherapy. We are developing proton spectroscopic techniques to determine the concentration of choline and other metabolites in cyst fluid and solid tissue elements to enhance lesion discrimination and are evaluating both spectroscopy and T2* estimation (for water content) to monitor treatment response.