Babar Vaqas

An MRS- and PET-guided biopsy tool for intraoperative neuronavigational systems

OBJECTIVE Glioma heterogeneity and the limitations of conventional structural MRI for identifying aggressive tumor components can limit the reliability of stereotactic biopsy and, hence, tumor characterization, which is a hurdle for developing and selecting effective treatment strategies. In vivo MR spectroscopy (MRS) and PET enable noninvasive imaging of cellular metabolism relevant to proliferation and can detect regions of more highly active tumor. Here, the authors integrated presurgical PET and MRS with intraoperative neuronavigation to guide surgical biopsy and tumor sampling of brain gliomas with the aim of improving intraoperative tumor-tissue characterization and imaging biomarker validation. METHODS A novel intraoperative neuronavigation tool was developed as part of a study that aimed to sample high-choline tumor components identified by multivoxel MRS and 18F-methylcholine PET-CT. Spatially coregistered PET and MRS data were integrated into structural data sets and loaded onto an intraoperative neuronavigation system. High and low choline uptake/metabolite regions were represented as color-coded hollow spheres for targeted stereotactic biopsy and tumor sampling. RESULTS The neurosurgeons found the 3D spherical targets readily identifiable on the interactive neuronavigation system. In one case, areas of high mitotic activity were identified on the basis of high 18F-methylcholine uptake and elevated choline ratios found with MRS in an otherwise low-grade tumor, which revealed the possible use of this technique for tumor characterization. CONCLUSIONS These PET and MRI data can be combined and represented usefully for the surgeon in neuronavigation systems. This method enables neurosurgeons to sample tumor regions based on physiological and molecular imaging markers. The technique was applied for characterizing choline metabolism using MRS and 18F PET; however, this approach provides proof of principle for using different radionuclide tracers and other MRI methods, such as MR perfusion and diffusion.

Health economic evaluation of a serum-based blood test for brain tumour diagnosis: exploration of two clinical scenarios

Objectives To determine the potential costs and health benefits of a serum-based spectroscopic triage tool for brain tumours, which could be developed to reduce diagnostic delays in the current clinical pathway. Design A model-based health pre-trial economic assessment. Decision tree models were constructed based on simplified diagnostic pathways. Models were populated with parameters identified from rapid reviews of the literature and clinical expert opinion. Setting Explored as a test in both primary and secondary care (neuroimaging) in the UK health service, as well as application to the USA. Participants Calculations based on an initial cohort of 10 000 patients. In primary care, it is estimated that the volume of tests would approach 75 000 per annum. The volume of tests in secondary care is estimated at 53 000 per annum. Main outcome measures The primary outcome measure was quality-adjusted life-years (QALY), which were employed to derive incremental cost-effectiveness ratios (ICER) in a cost-effectiveness analysis. Results Results indicate that using a blood-based spectroscopic test in both scenarios has the potential to be highly cost-effective in a health technology assessment agency decision-making process, as ICERs were well below standard threshold values of £20 000–£30 000 per QALY. This test may be cost-effective in both scenarios with test sensitivities and specificities as low as 80%; however, the price of the test would need to be lower (less than approximately £40). Conclusion Use of this test as triage tool in primary care has the potential to be both more effective and cost saving for the health service. In secondary care, this test would also be deemed more effective than the current diagnostic pathway.

Abstract LB-287: iKnife in neurosurgery: intraoperative real-time, in vivo biochemical characterization of brain tumors with high spatial resolution

The purpose of this study was to prove that rapid intraoperative tissue identification of brain tumours using Rapid Evaporative Ionization Mass Spectrometry (REIMS, used surgically as the iKnife) with high spatial resolution is possible in order to help establish a tissue diagnosis and to maximise the extent of tumour resection. A single centre prospective observational study was designed involving a consecutive series of patients undergoing craniotomy and resection of WHO grade II, III and IV tumours. A neuronavigation system was used to register iKnife readings for the first time during surgery for brain tumour resection. Precise intraoperative readings from different tumour zones were taken and compared to matched core biopsy samples verified by routine histopathology. This protocol worked well, allowing in-vivo mass spectrometry readings to be taken with accurate histology. Analysis of data from the first 6 cases shows distinct phospholipid spectral patterns for Grade II and IV tumours. An increased intensity of sulfatides were observed in the white matter of the grade II tumours. Our neuronavigational platform for the iKnife has revealed unique in-vivo spectra for different intrinsic brain tumours. As more cases are added to our spectral database we hope to describe in-vivo intra-tumoural variations which may shed important light into intrinsic brain tumour biology. Citation Format: Babar Vaqas, Julia Balog, Federico Roncaroli, Zoltan Takats, Kevin O9Neill. iKnife in neurosurgery: intraoperative real-time, in vivo biochemical characterization of brain tumors with high spatial resolution. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr LB-287. doi:10.1158/1538-7445.AM2015-LB-287