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Image Analysis Techniques of Hyperpolarized
13C MRI in Clinical Study
9/6/2019
Challenges in Clinical Management of Prostate Cancer
9/6/2019
Hyperpolarized-13C Imaging of Treatment Responses on Prostate Cancer Patients using 3D Dynamic CS-
EPSI Techniques
2
Unmet needs include:
▪ Determining Aggressiveness
▪ Monitoring Treatment Response
J Kurhanewicz, DB Vigneron, Magnetic Resonance
Spectroscopy of Prostate Cancer (2016)
MM Shevchuk et al., "The
Pathology of Prostatic
Carcinoma", Springer (2012)
Multiparametric MRI (mp-MRI)
Biopsy
Data Handling Pipeline
9/6/2019HMTRC3
HP-13C Human
Data Acquisition
Reconstruction and
Pre-processing
Quantitative
Data Analysis
• Hardware and Coils
• Pulse Sequences
• Imaging Resolution
• FOV Coverage
• Flip Angle Strategy
• Noise Pre-whitening
• Receiver Correction
• Transmitter Correction
• Coil Combination
• Peak Quantification
• Image Display
• SNR Masking
• ROI Analysis
• kPL Estimation
• Bolus Dynamics
Processing HP-13C Prostate Data
9/6/2019Presentation Title and/or Sub Brand Name Here4
Peak Quantification
▪ Magnitude data follows Rician noise model
▪ Phased data follows Gaussian noise model
9/6/2019HMTRC5
Phased Detection of Spectra
▪ Phased spectrum has zero-mean Gaussian noise
9/6/2019HMTRC6
Phased Spectrum
Phase Correction of HP-13C Spectra
9/6/2019HMTRC7
Nonlinear RF
Phase Correction Phase Correction
1st-order
Phase Correction
0th-order
Raw Spectra
On a peak-by-peak
basis
Other Quantification Techniques
▪ Lorentzian line fit
▪ LCModel type fit
9/6/2019HMTRC8
O’Haver et al., University of Maryland (1997)
Receiver Correction
9/6/2019HMTRC9
Noworolski et.al., JMR (2010); Chen et al., ISMRM (2018)
Receiver Profile
▪ Receiver profile of the endorectal coil simulated using Bio-Savart law
▪ Coil landmarks registered based on T2-FSE images
Receiver Correction – Case Study
▪ 68 y/o patient presented with biopsy confirmed G 4+3 prostate cancer in 8/16
cores (20-90% involvement) with PSA 15.4. No prior MRI.
▪ Combined HP-13C + SOC mpMRI at UCSF on 3T.
9/6/2019Presentation Title and/or Sub Brand Name Here10
T2w
ADC
Receiver Correction – Case Study
9/6/2019HMTRC11
Pyruvate
Before
Lactate
Chen et al., ISMRM (2018)
After
Receiver Correction – Case Study
▪ Bilateral base and right midgland prostate cancer involving PZ+TZ.
▪ Bilateral SVI, tumor extension to bladder base.
▪ HP-13C + mpMRI can be management-changing!
9/6/2019Presentation Title and/or Sub Brand Name Here12
▪ B1+ heterogeneity impacts quantification of metabolism
▪ B1+ map can be established from simulation or measurements
Transmitter Considerations
9/6/2019HMTRC13
“Clamshell” 13C Transmitter
Relative B1+
Original B1
+-insensitive
Chen et al., ISMRM (2017)
55Mn Fiducial Markers
Ohliger et al., ISMRM (2017)
Flip Angle Design
Image Display
▪ Wide variety of available tools
▪ SIVIC, OsiriX, brImage, ImageJ, MATLAB … and many more
9/6/2019HMTRC14
SIVIC OsiriX
Image Display
9/6/2019HMTRC15
brImage
OsiriX + ImageJ + MATLAB
▪ How would you like to show HP-13C images?
Pyruvate Lactate
Masking and ROIs
9/6/2019HMTRC16
0.100
0.075
0.050
0.025
0
(sec-1)
Pyruvate-to-Lactate kPL
1000
750
500
250
0
(AU)
Perfusion Maps
▪ Which biomarkers are we looking for?
▪ Metabolism-perfusion mismatch
Chen et al., Cancer Res. (2017)
SNR threshold = 3.5 SNR threshold = 5
0.03
0.02
0.01
0
(sec-1)
kPL
Masking and ROIs
9/6/2019HMTRC17
ROI analysis
▪ Statistics within each ROI
Quantification of Cancer Metabolism
▪ Pyruvate to lactate conversion kPL
▪ Accounts for metabolic exchange, variable flip angles & T1 relaxation
9/6/2019HMTRC18
0.030
0.025
0.020
0.015
0.010
(sec-1)
kPL
Maidens et al., IEEE Trans. Med. Imag.. (2018)
Summary
▪ No rocket science – the techniques are empirical and has plenty of flexibility.
▪ An iterative process between optimizing HP-13C acquisition, data processing
and image analysis.
▪ Develop different strategies based on the biomarkers of interest
9/6/2019HMTRC19

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UCSF Hyperpolarized MR #7-3: Prostate EPSI processing(2019)

  • 1. Image Analysis Techniques of Hyperpolarized 13C MRI in Clinical Study 9/6/2019
  • 2. Challenges in Clinical Management of Prostate Cancer 9/6/2019 Hyperpolarized-13C Imaging of Treatment Responses on Prostate Cancer Patients using 3D Dynamic CS- EPSI Techniques 2 Unmet needs include: ▪ Determining Aggressiveness ▪ Monitoring Treatment Response J Kurhanewicz, DB Vigneron, Magnetic Resonance Spectroscopy of Prostate Cancer (2016) MM Shevchuk et al., "The Pathology of Prostatic Carcinoma", Springer (2012) Multiparametric MRI (mp-MRI) Biopsy
  • 3. Data Handling Pipeline 9/6/2019HMTRC3 HP-13C Human Data Acquisition Reconstruction and Pre-processing Quantitative Data Analysis • Hardware and Coils • Pulse Sequences • Imaging Resolution • FOV Coverage • Flip Angle Strategy • Noise Pre-whitening • Receiver Correction • Transmitter Correction • Coil Combination • Peak Quantification • Image Display • SNR Masking • ROI Analysis • kPL Estimation • Bolus Dynamics
  • 4. Processing HP-13C Prostate Data 9/6/2019Presentation Title and/or Sub Brand Name Here4
  • 5. Peak Quantification ▪ Magnitude data follows Rician noise model ▪ Phased data follows Gaussian noise model 9/6/2019HMTRC5
  • 6. Phased Detection of Spectra ▪ Phased spectrum has zero-mean Gaussian noise 9/6/2019HMTRC6 Phased Spectrum
  • 7. Phase Correction of HP-13C Spectra 9/6/2019HMTRC7 Nonlinear RF Phase Correction Phase Correction 1st-order Phase Correction 0th-order Raw Spectra On a peak-by-peak basis
  • 8. Other Quantification Techniques ▪ Lorentzian line fit ▪ LCModel type fit 9/6/2019HMTRC8 O’Haver et al., University of Maryland (1997)
  • 9. Receiver Correction 9/6/2019HMTRC9 Noworolski et.al., JMR (2010); Chen et al., ISMRM (2018) Receiver Profile ▪ Receiver profile of the endorectal coil simulated using Bio-Savart law ▪ Coil landmarks registered based on T2-FSE images
  • 10. Receiver Correction – Case Study ▪ 68 y/o patient presented with biopsy confirmed G 4+3 prostate cancer in 8/16 cores (20-90% involvement) with PSA 15.4. No prior MRI. ▪ Combined HP-13C + SOC mpMRI at UCSF on 3T. 9/6/2019Presentation Title and/or Sub Brand Name Here10 T2w ADC
  • 11. Receiver Correction – Case Study 9/6/2019HMTRC11 Pyruvate Before Lactate Chen et al., ISMRM (2018) After
  • 12. Receiver Correction – Case Study ▪ Bilateral base and right midgland prostate cancer involving PZ+TZ. ▪ Bilateral SVI, tumor extension to bladder base. ▪ HP-13C + mpMRI can be management-changing! 9/6/2019Presentation Title and/or Sub Brand Name Here12
  • 13. ▪ B1+ heterogeneity impacts quantification of metabolism ▪ B1+ map can be established from simulation or measurements Transmitter Considerations 9/6/2019HMTRC13 “Clamshell” 13C Transmitter Relative B1+ Original B1 +-insensitive Chen et al., ISMRM (2017) 55Mn Fiducial Markers Ohliger et al., ISMRM (2017) Flip Angle Design
  • 14. Image Display ▪ Wide variety of available tools ▪ SIVIC, OsiriX, brImage, ImageJ, MATLAB … and many more 9/6/2019HMTRC14 SIVIC OsiriX
  • 15. Image Display 9/6/2019HMTRC15 brImage OsiriX + ImageJ + MATLAB ▪ How would you like to show HP-13C images? Pyruvate Lactate
  • 16. Masking and ROIs 9/6/2019HMTRC16 0.100 0.075 0.050 0.025 0 (sec-1) Pyruvate-to-Lactate kPL 1000 750 500 250 0 (AU) Perfusion Maps ▪ Which biomarkers are we looking for? ▪ Metabolism-perfusion mismatch Chen et al., Cancer Res. (2017) SNR threshold = 3.5 SNR threshold = 5 0.03 0.02 0.01 0 (sec-1) kPL
  • 17. Masking and ROIs 9/6/2019HMTRC17 ROI analysis ▪ Statistics within each ROI
  • 18. Quantification of Cancer Metabolism ▪ Pyruvate to lactate conversion kPL ▪ Accounts for metabolic exchange, variable flip angles & T1 relaxation 9/6/2019HMTRC18 0.030 0.025 0.020 0.015 0.010 (sec-1) kPL Maidens et al., IEEE Trans. Med. Imag.. (2018)
  • 19. Summary ▪ No rocket science – the techniques are empirical and has plenty of flexibility. ▪ An iterative process between optimizing HP-13C acquisition, data processing and image analysis. ▪ Develop different strategies based on the biomarkers of interest 9/6/2019HMTRC19