Project details

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Novel gene mutation imaging with 2-HG MR spectroscopy in low grade gliomas; a validation study.

Keywords:
imaging oncology Radiology

Researchers:
prof. dr. R.A. Dierckx
dr. A van der Hoorn
dr. P.J. van Laar

Nature of the research:
This research is conducted at the department of radiology in the UMCG in close collaboration with tin department of neurology, neurosurgery, laboratory medicine and pathology. The current project will be embedded in the research line: Diagnosis, treatment-planning and -evaluation in brain and head/neck tumours. This research line is a main research focus of the department of radiology as part of the Medical Imaging Center (MIC) in the UMCG. For MPDI students it fits to both the ‘oncology’ and ‘medical neurosciences and neurological diseases’ track. The current project will consist of a prospective patient study.

Fields of study:
neurology oncology radiology

Background / introduction
Gliomas are the most common primary brain tumour. The incidence is relatively low with 7 per 100.000 (1), however they account for a large number of lost of healthy life years (2). Gliomas are divided in low and high grade gliomas. Low grade gliomas occur in a relatively young population of 30-50 years (3). Surgery in not always possible as tumours might be located next to an eloquent brain area. Treatment with only chemo- and radiotherapy is preferred in these cases. However, the diagnosis should be firmly established beforehand. A biopsy is currently the only option to establish the diagnosis. However a biopsy is invasive and has associated complications and mortality. The complication rate of a biopsy of a primary brain tumour is 4,5% (4). This is most commonly a haemorrhage which is also responsible for most of the mortality of about 2%. A non-invasive method to assess the diagnosis is clearly wanted.

A novel MR spectroscopy method might help. MR spectroscopy is able to differentiate different metabolites based upon the resonance frequency of these metabolites. The majority (80-90%) of the low grade gliomas have a isocitrate dehydrogenases-1 (IDH-1) or ID-2 gene mutation (5,6). An IDH mutation always result in the production of the onometabolite 2-hydrocyglutarate (2-HG). 2-HG can be measured with MR spectroscopy (7). 2-HG is characteristic for low grade gliomas only and might provide a non-invasive alterative to establish the diagnosis.

2-HG is limited investigates thus far, but provide the unique opportunities to visualise a gene mutation with MR and establish the diagnosis of low grade gliomas non-invasively. However, further validation of 2-HG MR spectroscopy is needed. The correlation between in vivo 2-HG MR spectroscopy and ex vivo 2-HG concentration should be validated and is the subject of the current project.
Research question / problem definition
What is the correlation between 2-HG MR spectroscopy and IDH mutation status in low grade gliomas? What is the correlation between the concentration of 2-HG on MR spectroscopy and the 2-HG concentration of ex vivo tissue?
Workplan
research project. 2-HG MR spectroscopy already has been tested on our MR scanners and is feasible (see figure 1). Slight optimisation of the post processing might be needed. The student will be supervised by MR spectroscopy expert for this part. Supervisions will be also provided by clinical experts and the student will work in close collaboration with the department of laboratory medicine. A pro-active work attitude is expected from the student.

To acquire a clinical view on the patients involved in this research, it will be possible for the student to visit the neurology department and see the out patients visits. Joining the neuro-radiologist during reporting is also possible. Joining the multidisciplinary team discussions on Wednesdays furthers adds to the clinical knowledge within this research subject.
References
1. Ostrom QT, Gittleman H, Xu J et al. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2009–2013. Neuro Oncol 2016; 18: v1-v75.
2. Burnet NG, Jefferies SJ, Benson RJ, Hunt DP, Treasure FP. Years of life lost (YLL) from cancer is an important measure of population burden – and should be considered when allocating research funds. Br J Cancer 2005; 31: 241-245.
3. Van den Bent MJ, Wefel JS, Schiff D, et al. Response assessment in neuro-oncology (a report of the RANO group): assessment of outcome in trials of diffuse low-grade gliomas. Lancet Oncol. 2011;12(6):583-593.
4. Malone H, Yang J, Hershman DL, Wright JD, Bruce JN, Neugut AI. Complications following stereotactic biopsy needle biopsy of intracranial tumors. World Neurosurg 2015; 84: 1084-1089.
5. Sanson M, Marie Y, Paris S, et al. Isocitrate dehydrogenase 1 codon 132 mutation is an important prognostic biomarker in gliomas. J Clin Oncol 2009; 27: 4150-4154.
6. Yan H, Parsons DW, Jin G, et al. IDH1 and IDH2 mutations in gliomas. N Engl J Med 2009; 360: 765-773.
7. Leather T, Jenkinson MD, Das K, Poptani H. Magnetic resonance spectroscopy for detection of 2-hydroxyglutarate as a biomarker for IDH mutation in gliomas. Metabolites 2017; 7: 1-16.
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