Transcript Document

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