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 Quantitative MRSI to predict early response to SAHA therapy in GBM management Pseudoprogression & Pseudoresponse Reprograms tumor genes to carry out normal activity. Blocks abnormal HDAC and makes tumor DNA receptive to attack by temozolomide (TMZ). Stops tumor growth & encourages tumor cells to behave more like normal brain cells TMZ tumor cell killing is increased with SAHA SAHA +TMZ SAHA opens up tumor DNA, providing better access to TMZ 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 mm 3 (108 l) The internal water signal is collected as a denominator to obtain absolute metabolite concentrations in an interleaved manner, which does Before Week 2 Week 11 Week 20 Gd-MRI Cho/NAA ratio changes with SAHA+XRT+TMZ Respond er Non- Responder Trial design: New GBM Before Week 2 Before Week 11 Gd-MRI SAHA+TMZ+XRT Wk 6 SAHA+TMZ Rest Wk 20 MRSI MRSI MRSI Clinical MRI Clinical MRI Wk 0 Wk 11 Blobs Segmented Tumors F H 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) CCC = 0.995 ± 0.002 95% CI = 0.990 - 0.997 CCC = 0.985 ± 0.005 95% CI = 0.972 - 0.992 Dice = 0.916 ± 0.012 (CI 95 = 0.891 - 0.940) MED = 0.142 ± 0.023 (CI 95 = 0.096 – 0.188) Dice = 0.640 ± 0.040 (CI 95 = 0.559 – 0.722) MED = 3.110 ± 0.837 (CI 95 = 1.411 – 4.811) Pre-tumor resection Pre-tumor resection Post-tumor resection Post-tumor resection Fuzzy 3 Computed Volume (cm 3 ) Manual Segmentation Volume (cm 3 ) Fuzzy 3 Computed Volume (cm 3 ) Manual Segmentation Volume (cm 3 ) 3D NAA Whole Brain Image co-registration platform Unbiased-Tumor segmentation tool Segmentation tool validatio Concordance Correlation Coefficient Dice Similarity Index Mean Euclidean Distance Bland Altman Plot SAHA: Epigenetic Drug SAHA SAHA Other applications of our too Guidance for stereotactic biopsy & surgery in Stealth Neuro- navigation System Guidance for radiotherapy dose planning Progress: Accepted Publication Cordova et al. Translational Oncology 20 Shim et al. Am J Roentgenology 2014