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

+TMZSAHA 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 mm3 (108 l)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

Before Week 2 Week 11 Week 20

Gd-MRI

Cho/NAA ratio changes with SAHA+XRT+TMZ

Responder

Non-Responder

Trial design: New GBM

Before Week 2 Before Week 11

Gd-MRI

SAHA+TMZ+XRT

Wk 6

SAHA+TMZRest

Wk 20

MRSI MRSI MRSI

Clinical MRI Clinical MRI

Wk 0 Wk 11

Blobs Segmented TumorsF

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 ± 0.00295% CI = 0.990 - 0.997

CCC = 0.985 ± 0.00595% CI = 0.972 - 0.992

Dice = 0.916 ± 0.012 (CI95 = 0.891 - 0.940)MED = 0.142 ± 0.023 (CI95 = 0.096 – 0.188)

Dice = 0.640 ± 0.040 (CI95 = 0.559 – 0.722)MED = 3.110 ± 0.837 (CI95 = 1.411 – 4.811)

Pre-tumor resectionPre-tumor resection

Post-tumor resectionPost-tumor resection

Fuzzy 3 Computed Volume (cm3)

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Fuzzy 3 Computed Volume (cm3)

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3D NAAWhole Brain

Image co-registration platform

Unbiased-Tumor segmentation tool

Segmentation tool validation Concordance Correlation

Coefficient Dice Similarity Index Mean Euclidean Distance Bland Altman Plot

SAHA: Epigenetic Drug

SAHA

SAHA

Other applications of our tools

Guidance for stereotactic biopsy & surgery in Stealth Neuro-navigation System

Guidance for radiotherapy dose planning

Progress: Accepted PublicationsCordova et al. Translational Oncology 2014Shim et al. Am J Roentgenology 2014