Lipids Detected by 1H Magnetic Resonance Spectroscopy as Brain Tumour Biomarkers
Lead Research Organisation:
University of Birmingham
Department Name: Neuroscience
Abstract
We use Proton Magnetic Resonance Spectroscopy (MRS) to examine the biochemical nature of lipid species in paediatric brain tumours. Brain tumours are the most common form of solid tumours in the child population. Clinical management of paediatric brain tumour patients would benefit from imaging techniques able to indicate tumour aggressiveness in regard to growth and invasion as well as allowing assessment of treatment response.
Our goal is to find a link between the MRS lipids and clinical behaviour of brain cancer. Preclinical and clinical studies have indicated that saturated lipids by MRS are indicative of the degree of malignancy. Similarly, during successful therapy MRS signals from unsaturated lipids change indicating cell death at an early stage.
The work will be carried out in one of the largest children’s cancer centers in the UK. The MRS results recorded from tumours will be compared with those obtained from tumour tissue collected at operations. Clinical information, including patient outcome and event-free survival, will be compared with MRS lipids and other lipid analyses from tumours.
We expect that the results from the MRS project will allow doctors to predict how aggressive a brain tumour is and how well it will respond to treatment without a biopsy. Repeating MRS during treatment it is expected should provide an efficient means for monitoring treatment response, making it possible to adjust treatment to achieve an optimal outcome without delay.
Our goal is to find a link between the MRS lipids and clinical behaviour of brain cancer. Preclinical and clinical studies have indicated that saturated lipids by MRS are indicative of the degree of malignancy. Similarly, during successful therapy MRS signals from unsaturated lipids change indicating cell death at an early stage.
The work will be carried out in one of the largest children’s cancer centers in the UK. The MRS results recorded from tumours will be compared with those obtained from tumour tissue collected at operations. Clinical information, including patient outcome and event-free survival, will be compared with MRS lipids and other lipid analyses from tumours.
We expect that the results from the MRS project will allow doctors to predict how aggressive a brain tumour is and how well it will respond to treatment without a biopsy. Repeating MRS during treatment it is expected should provide an efficient means for monitoring treatment response, making it possible to adjust treatment to achieve an optimal outcome without delay.
Technical Summary
1H magnetic resonance spectroscopy (MRS) reveals resonances from CH2/CH3 groups of saturated mobile lipids in brain tumours, but not in the healthy brain parenchyma. Evidence from the applicants and others links the 1H MRS detectable lipids to poor prognosis. Our data from experimental gliomas show that 1H MRS signals from polyunsaturated lipids (PUFA) are excellent non-invasive biomarkers for apoptosis induced by cytotoxic therapy. The proposal is to qualify biomarker value of 1H MRS detected saturated and PUFA lipids. Hypotheses, claiming that (a) saturated 1H MRS lipids are prognostic biomarkers and (b) PUFAs biomarkers for therapy monitoring, will be examined. The project involves both retrospective (80 patients) and prospective (~35 patients annually) paediatric brain tumour cohorts of Birmingham Children Hospital (BCH) as clinical patient population. Paediatic patients undergo regular 1H MRS during the follow-up at BCH, extending to six years for a subset of cases, and tissue specimens are obtained from about 80% of tumours. State-of-the-art in vivo MRS technology, data processing and lipid analyses, including MALDI-MS technique on histological specimens, will be used. The project involves two commercial partners (Waters, MA, USA and MRSTools Inc., Finland). The 1H MRS non-invasive biomarkers are expected to improve patient management, reduce need for invasive diagnostic procedures and enable efficient objective therapy monitoring. In long term, specific molecular biomarkers may be linked to targeted new therapeutic agents.
