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Emory University: PIs: Hyunsuk Shim, Hui-Kuo Shu, Jeffrey J. Olson, Xiaoping P. Hu

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

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Emory University: PIs: Hyunsuk Shim, Hui-Kuo Shu, Jeffrey J. Olson, Xiaoping P. Hu

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  1. 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 VoloschinJohns Hopkins University: PI: Peter Barker University of Miami: Consultant: Andrew Maudsley Co-Inv: Matthias Holdhoff, Stuart Grossman, Doris Lin, Lawrence Kleinberg, Fausto Rodriguez Image co-registration platform Post-tumor resection Pseudoprogression & Pseudoresponse CCC = 0.985 ± 0.005 95% CI = 0.972 - 0.992 3D NAA Whole Brain Manual Segmentation Volume (cm3) • 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 Fuzzy 3 Computed Volume (cm3) Dice = 0.640 ± 0.040 (CI95 = 0.559 – 0.722) MED = 3.110 ± 0.837 (CI95 = 1.411 – 4.811) Segmentation tool validation SAHA: Epigenetic Drug Cho/NAA ratio changes with SAHA+XRT+TMZ • Concordance Correlation Coefficient • Dice Similarity Index • Mean Euclidean Distance • Bland Altman Plot Reprograms tumor genes to carry out normal activity. Blocks abnormal HDAC and makes tumor DNA receptive to attack by temozolomide (TMZ). • 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) Responder Before Week 2 Week 11 Week 20 Unbiased-Tumor segmentation tool Other applications of our tools SAHA Blobs Segmented Tumors Stops tumor growth & encourages tumor cells to behave more like normal brain cells SAHA F SAHA opens up tumor DNA, providing better access to TMZ SAHA TMZ tumor cell killing is increased with SAHA +TMZ Trial design: New GBM H Gd-MRI MRSI MRSI MRSI SAHA+TMZ+XRT SAHA+TMZ Rest Non-Responder Wk 0 Wk 6 Wk 11 Wk 20 Before Week 2 Before Week 11 CCC = 0.995 ± 0.002 95% CI = 0.990 - 0.997 Pre-tumor resection Clinical MRI Clinical MRI Dice = 0.916 ± 0.012 (CI95 = 0.891 - 0.940) MED = 0.142 ± 0.023 (CI95 = 0.096 – 0.188) • 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 Manual Segmentation Volume (cm3) • Guidance for stereotactic biopsy & surgery in Stealth Neuro-navigation System • Guidance for radiotherapy dose planning Progress: Accepted Publications • Cordova et al. Translational Oncology 2014 • Shim et al. Am J Roentgenology 2014 Fuzzy 3 Computed Volume (cm3) Gd-MRI

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