Article Methods Research Question Results GBM Parametric Response Map/Quantitative MRI 1 - Prospective Analysis of Parametric Response Map– Derived MRI Biomarkers: Identification of Early and Distinct Glioma Response Patterns Not Predicted by Standard Radiographic Assessment 2Updated Response Assessment Criteria for HighGrade Gliomas: Response Assessment in Neuro-Oncology Working Group 45 patients with grade 3 or 4 gliomas were taken for experimental parametric response mapping through quantitative ADC and rCBV MRI’s. Patients were evaluated pretreatment, 3 and ten weeks into therapy. Can parametric response mapping using perfusion and diffusion- weighted MRI brain tumor maps combined with multiple imaging treatments be used to increase clinical application Quantitative MRI’s were indeed quite useful/accurate in predicting accurate life longevity measurements. T1-weighted images that were contralateral to the affected area were used to create a PMR and relative cerebral blood volume and flow were both calculated by normalizing the RCB/RCF map values. These ultimately created a real time image that more closely monitored progression and efficacy of treatment X X By taking several radioneurologists and oncologists, the McDonald criteria have been recognized as outdated. Through the use of CT/MRI scanning, new criteria are being created. Can new criteria for high grade glioma patients be created as to fully cover all grounds of radiology imaging sequencing mechanisms to measure therapy productivity The Macdonald criteria were critically evaluated and assessed from multiple angles from multiple professions. The addition of definition of cross sectional diameter and the inclusion of the non-enhancing section on a T2 weighted dynamic susceptibility contrast MR image improved prognosis calculations by a margin of 15-20 percent X X Enhanced Cell Detection Treatment Efficacy X 3 Because both EphA2 and EphrinA1 display specific patterns of expression, it is necessary to measure them at critical points of peak expression, and monitor the relationship between protein/binding expression through the use of miniature nuclear magnetic resonance imaging with the progression of the GBM cells Can the protein EphA2 and its binding ligand EphrinA1 be used as potential biomarkers by the use of expression monitoring to better understand GBM cells. If so, can it be used to explain GBM pathogenesis or for molecular therapeutics against GBM EphA2 was found to be significantly overexpressed in GBM patients, which is consistent with other findings in lung, ovarian, colon, and liver cancers. It was found that when EphA2 was unable to bind to the extremely underexpressed complementary ligand, that the tumor cells became far more aggressive. This is thought to be due to the unstable cell-cell contacts within cancer tissue, which would in turn limit the ability of the EphA2 to come in contact with the already thinly spread ligand. X X 4 Using a scaled NMR imaging system in combination with a newly engineered micro-fluidic chip, blood can be taken from a high grade glioma patient that has been injected with GBM targeting nano-particles that can then be studied by researchers Are these membrane-bound microvesicles shed by tumors in GBM patients a key to creating a real-time monitoring strategy for both the progression of the tumor, as well as treatment? If so, what is the next step necessary to making this happen. Researchers found that GBM patients had highdensity quantities of these microvesicles and were able to gain rudimentary results. Nanoparticles have not been developed to the point where we can study the movement and development of tumor cells and microvesicle interaction, however it was able to be determined that they can help us predict primary tumor mutations as well as treatment induced changes. In combination with MRI imaging, it is a big step towards monitoring pseudoprogression X X EphA2 as a novel molecular marker and target in Glioblastoma Multiforme Protein typing of circulating microvesicles allows real-time monitoring of glioblastoma therapy X 5 T2 weighted dynamic susceptibility contrast magnetic resonance imaging in combination with normalized apparent diffusion coefficient and relative cerebral blood flow/volume levels to create a parametric response mapping of tumor progression Since 20-30 percent of high grade glioma patients are diagnosed falsely under pseudoprogression, researchers wonder if PMR can help to clarify MRI results Using the normalized values of the rCBV/rCBF mapping sequences, the detection of pseudoprogression was increased, and 6-8 percent of patients were correctly diagnosed out of the 20-30 originally put in the pseudo pile. X 6 Injection of targeting nanoparticles into a patient’s bloodstream in order to measure platelet interactions with the blood-brain barrier. Can nanoparticles be used to increase sensitivity of cell detection, specifically antibodies crossing the blood-brain barrier? If so, can it be used to fight tumor cells in Glioblastoma Multiforme patients The results of these tests were largely inconclusive, although there is a good lead in advancement in a micro-fluidic chip (see article 4). The application is promising for biomedical research X Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high grade glioma patients Bioorthogonal chemistry amplifies nanoparticle binding and enhances the sensitivity of cell detection X X X