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Quantitative MRSI to predict early response to SAHA therapy in GBM management Emory University: PIs: Hyunsuk Shim, Hui-Kuo Shu, Jeffrey J. Olson, Xiaoping P. Hu Co-Inv: Tim Fox, Eduard Schreibmann, Chad A. Holder, Ying Guo, Andrew H. Miller, Daniel Brat, Alfredo Voloschin Johns Hopkins University: PI: Peter Barker University of Miami: Consultant: Andrew Maudsley Co-Inv: Matthias Holdhoff, Stuart Grossman, Doris Lin, Lawrence Kleinberg, Fausto Rodriguez Post-tumor resection Image co-registration platform Manual Segmentation Volume (cm3) Pseudoprogression & Pseudoresponse 3D NAA Whole Brain SAHA: Epigenetic Drug Cho/NAA ratio changes with SAHA+XRT+TMZ Reprograms tumor genes to carry out normal activity. Blocks abnormal HDAC and makes tumor DNA receptive to attack by temozolomide (TMZ). Responder Before Week 2 Week 11 Week 20 Multi-modality image registration (rigid & deformable) Quantitative tools for RT planning (SUV, Intensity thresholding & clustering) Atlas-based segmentation methods for CT and MR Supports DICOM RT, CBCT, CT, MR, PET and SPECT FDA 510k Clearance Recent UCSF study found Velocity AI to have the smallest mean spatial error out of 11 deformable image registration programs that were evaluated (Kirby et al. Med Phys 2013) Unbiased-Tumor segmentation tool SAHA SAHA SAHA opens up tumor DNA, providing better access to TMZ SAHA +TMZ Blobs Stops tumor growth & encourages tumor cells to behave more like normal brain cells Segmented Tumors Wk 0 Clinical MRI Wk 6 Segmentation tool validation Concordance Correlation Coefficient Dice Similarity Index Mean Euclidean Distance Bland Altman Plot Other applications of our tools H Gd-MRI MRSI SAHA+TMZ Wk 11 Non-Responder Wk 20 Before Week 2 Before Week 11 Clinical MRI Technical Details: 32-channel phased-array head coil at 3T (Siemens) 3D whole brain EPSI/GRAPPA (12 min scan time) TR/TE: 1550/17.6 ms, nominal voxel size: 4.4x4.4x5.6 mm3 (108 ml) The internal water signal is collected as a denominator to obtain absolute metabolite concentrations in an interleaved manner, which does not increase the total scan time Gd-MRI Manual Segmentation Volume (cm3) Rest Dice = 0.640 ± 0.040 (CI95 = 0.559 – 0.722) MED = 3.110 ± 0.837 (CI95 = 1.411 – 4.811) TMZ tumor cell killing is increased with SAHA MRSI SAHA+TMZ+XRT Fuzzy 3 Computed Volume (cm3) F Trial design: New GBM MRSI CCC = 0.985 ± 0.005 95% CI = 0.972 0.992 CCC = 0.995 ± 0.002 95% CI = 0.990 0.997 Pre-tumor resection Dice = 0.916 ± 0.012 (CI95 = 0.891 - 0.940) MED = 0.142 ± 0.023 (CI95 = 0.096 – 0.188) Guidance for stereotactic biopsy & surgery in Stealth Neuro-navigation System Guidance for radiotherapy dose planning Progress: Accepted Publications Fuzzy 3 Computed Volume (cm3) Cordova et al. Translational Oncology 2014 Shim et al. Am J Roentgenology 2014