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Using EPI to investigate HP [1-13C]pyruvate
metabolism in glioma patients and healthy
volunteers
Adam W Autry, Jeremy W Gordon, Hsin-Yu Chen, Daniele
Mammoli, Marisa LaFontaine, Javier Villanueva-Meyer, Susan M
Chang, Duan Xu, Peder EZ Larson, Daniel B Vigneron,
Sarah J Nelson, and Yan Li
University of California, San Francisco (UCSF)
[1] Park et al, MRM 2018, [2] Miloushev et al, Cancer Res. 2018
Hyperpolarized (HP) 13C Imaging
Chemical shift (ppm)
190 185 180 175 170 165 160
pyruvate
Dynamic Echo Planar Imaging (EPI)
[3] Gordon et al, MRM, 2019
SPSP excitation
RF
Gz
Gy
Gx
TR/TE = 62.5 ms / 21.7ms
Spatial resolution = 2.88 – 8 cm3
Temporal resolution: 3s
13Cspectra
Chemical shift (ppm)
185 180 175 170 165 160
HP-13CEPI
pyruvate
𝛼=20∘
lactate
𝛼=30∘
bicarb
𝛼=30∘
Dynamic frequency-selective 13C EPI
Pyr
Lac
Bic
T1w
2D multi-slice EPI
Noise-only data
Nyquist Ghost
Correction
Prewhitening Recon
1
ky/Echo#
Uncorrected Corrected
2
3
4
5
6
7
8
Noise Covariance Matrix
8
7
6
5
4
3
2
1
1 2 3 4 5 6 7 8ch
Channel
EPI Processing Framework
Coil Combination
Voxel-wise
phasing
AUC Images /
kPL, kPB Estimation
Combined Pyr
ch1
ch3
ch4
ch5
ch6ch7
ch8
AUC
Pyruvate
AUC
Lactate
AUC
Bicarb
0.036
0.018
0
ch2
kPL(sec-1)
Optimal Weights Coil Combination
𝑰 𝒎𝒆𝒕,𝒅𝒚𝒏 𝒙, 𝒚, 𝒄𝒐𝒊𝒍, 𝒔𝒍𝒊𝒄𝒆, 𝒇𝒓𝒂𝒎𝒆 % complex data after FFT
𝑰 𝒑𝒚𝒓 =
𝒇𝒓𝒂𝒎𝒆=𝟏
𝟐𝟎
𝑰 𝒑𝒚𝒓,𝒅𝒚𝒏 % temporally-summed RefPeak map
𝑰 𝒑𝒚𝒓,𝑺𝑶𝑺 =
𝒄𝒐𝒊𝒍=1
32
|𝑰 𝒑𝒚𝒓(𝒙, 𝒚, 𝒄𝒐𝒊𝒍, 𝒔𝒍𝒊𝒄𝒆)|2 % normalization factor for RefPeak map
𝒘𝒆𝒊𝒈𝒉𝒕 =
𝑰 𝒑𝒚𝒓
𝑰 𝒑𝒚𝒓,𝑺𝑶𝑺
% complex RefPeak coil weights
𝑰 𝒄𝒐𝒎𝒃 =
𝒄𝒐𝒊𝒍=𝟏
𝟑𝟐
𝒘𝒆𝒊𝒈𝒉𝒕∗ 𝒙, 𝒚, 𝒄𝒐𝒊𝒍, 𝒔𝒍𝒊𝒄𝒆 𝑰 𝒎𝒆𝒕,𝒅𝒚𝒏
% weighted-sum combination
% peformed for each frame
Voxel-wise Phasing
S = |𝑨𝑼𝑪𝒍𝒂𝒄|𝒆𝒊∡(𝑨𝑼𝑪 𝒑𝒚𝒓 𝑨𝑼𝑪𝒍𝒂𝒄
∗
)
𝚫𝝓 𝒑𝒚𝒓−𝒍𝒂𝒄 = −( ∡𝑺 )|𝑺|
𝑰𝒍𝒂𝒄,𝒑𝒉𝒂𝒔𝒆𝒅 = 𝑰𝒍𝒂𝒄,𝒅𝒚𝒏 𝒆−𝒊(∡𝑨𝑼𝑪 𝒑𝒚𝒓+𝚫𝝓 𝒑𝒚𝒓−𝒍𝒂𝒄)
𝑰 𝒑𝒚𝒓,𝒑𝒉𝒂𝒔𝒆𝒅 = 𝑰 𝒑𝒚𝒓,𝒅𝒚𝒏 𝒆−𝒊∡𝑨𝑼𝑪 𝒑𝒚𝒓
𝑰 𝒃𝒊𝒄,𝒑𝒉𝒂𝒔𝒆𝒅 = 𝑰 𝒃𝒊𝒄,𝒅𝒚𝒏 𝒆−𝒊∡𝑨𝑼𝑪 𝒃𝒊𝒄
% phase difference between pyr and lactate
% directly phase pyruvate (highest SNR)
% phase lactate relative to pyruvate
% directly phase bicarbonate to avoid flow
% affects from blood
% assume no temporal change in phase
Regions of Interest
NORMAL-APPEARING
WHITE MATTER
PUTATIVE TUMOR:
T2 LESIONT2LWM
REGIONS OF INTEREST
Normal-appearing
white matter (NAWM)
T2 Lesion (T2L)
Kinetic traces and fitting: NAWM
4
3
0
Post-injection time (s)
10 20 30 40 50 60
0
White matter traces
0
1
2
5
6
HP-13Csignal(AU)
kPL& kPB Maps with ROIs
0.03
0.015
0 kPL(s-1)
0.0104
0.0052
kPB(s-1)
0
White matter traces
6
)
[7] Crane et al, SIVIC visualization
Healthy Control
0
kPL(s-1)kPB(s-1)
0.028
0.014
0
0.0078
0.0039
B
A
0.022
32ch
Test / Re-Test kPL,NAWM : 0.017 ± 0.001 / 0.017 ± 0.002 s-1
Test 30-min Re-Test: Healthy Control0
kP
B
kPL(s-1)
0.022
0.011
0
Re-Test:24chTest:32ch
Test / Re-Test kPL,NAWM : 0.017 ± 0.001 / 0.017 ± 0.002 s-1
Serial HP Data
0.036+
kPL(s-1)
0.018
0
0.009
0.027
TP8+bevTP7+bevTP5TP6
0 10 20 30 40 50 0 10 20 30 40 50
Time (s) Time (s)
2000
4000
6000
8000
10000
2000
1000
3000
HP-13CSignal(AU)
Pyruvate
Lactate
Bicarbonate
Post-bevacizumabPre-bevacizumab
Recirculation
Normal-appearing white matter
Patient with glioma before and
during treatment with anti-
angiogenic agent bevacizumab

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UCSF Hyperpolarized MR #7-2: Brain EPI processing(2019)

  • 1. Using EPI to investigate HP [1-13C]pyruvate metabolism in glioma patients and healthy volunteers Adam W Autry, Jeremy W Gordon, Hsin-Yu Chen, Daniele Mammoli, Marisa LaFontaine, Javier Villanueva-Meyer, Susan M Chang, Duan Xu, Peder EZ Larson, Daniel B Vigneron, Sarah J Nelson, and Yan Li University of California, San Francisco (UCSF)
  • 2. [1] Park et al, MRM 2018, [2] Miloushev et al, Cancer Res. 2018 Hyperpolarized (HP) 13C Imaging Chemical shift (ppm) 190 185 180 175 170 165 160 pyruvate
  • 3. Dynamic Echo Planar Imaging (EPI) [3] Gordon et al, MRM, 2019 SPSP excitation RF Gz Gy Gx TR/TE = 62.5 ms / 21.7ms Spatial resolution = 2.88 – 8 cm3 Temporal resolution: 3s 13Cspectra Chemical shift (ppm) 185 180 175 170 165 160 HP-13CEPI pyruvate 𝛼=20∘ lactate 𝛼=30∘ bicarb 𝛼=30∘
  • 4. Dynamic frequency-selective 13C EPI Pyr Lac Bic T1w
  • 5. 2D multi-slice EPI Noise-only data Nyquist Ghost Correction Prewhitening Recon 1 ky/Echo# Uncorrected Corrected 2 3 4 5 6 7 8 Noise Covariance Matrix 8 7 6 5 4 3 2 1 1 2 3 4 5 6 7 8ch Channel EPI Processing Framework
  • 6. Coil Combination Voxel-wise phasing AUC Images / kPL, kPB Estimation Combined Pyr ch1 ch3 ch4 ch5 ch6ch7 ch8 AUC Pyruvate AUC Lactate AUC Bicarb 0.036 0.018 0 ch2 kPL(sec-1)
  • 7. Optimal Weights Coil Combination 𝑰 𝒎𝒆𝒕,𝒅𝒚𝒏 𝒙, 𝒚, 𝒄𝒐𝒊𝒍, 𝒔𝒍𝒊𝒄𝒆, 𝒇𝒓𝒂𝒎𝒆 % complex data after FFT 𝑰 𝒑𝒚𝒓 = 𝒇𝒓𝒂𝒎𝒆=𝟏 𝟐𝟎 𝑰 𝒑𝒚𝒓,𝒅𝒚𝒏 % temporally-summed RefPeak map 𝑰 𝒑𝒚𝒓,𝑺𝑶𝑺 = 𝒄𝒐𝒊𝒍=1 32 |𝑰 𝒑𝒚𝒓(𝒙, 𝒚, 𝒄𝒐𝒊𝒍, 𝒔𝒍𝒊𝒄𝒆)|2 % normalization factor for RefPeak map 𝒘𝒆𝒊𝒈𝒉𝒕 = 𝑰 𝒑𝒚𝒓 𝑰 𝒑𝒚𝒓,𝑺𝑶𝑺 % complex RefPeak coil weights 𝑰 𝒄𝒐𝒎𝒃 = 𝒄𝒐𝒊𝒍=𝟏 𝟑𝟐 𝒘𝒆𝒊𝒈𝒉𝒕∗ 𝒙, 𝒚, 𝒄𝒐𝒊𝒍, 𝒔𝒍𝒊𝒄𝒆 𝑰 𝒎𝒆𝒕,𝒅𝒚𝒏 % weighted-sum combination % peformed for each frame
  • 8. Voxel-wise Phasing S = |𝑨𝑼𝑪𝒍𝒂𝒄|𝒆𝒊∡(𝑨𝑼𝑪 𝒑𝒚𝒓 𝑨𝑼𝑪𝒍𝒂𝒄 ∗ ) 𝚫𝝓 𝒑𝒚𝒓−𝒍𝒂𝒄 = −( ∡𝑺 )|𝑺| 𝑰𝒍𝒂𝒄,𝒑𝒉𝒂𝒔𝒆𝒅 = 𝑰𝒍𝒂𝒄,𝒅𝒚𝒏 𝒆−𝒊(∡𝑨𝑼𝑪 𝒑𝒚𝒓+𝚫𝝓 𝒑𝒚𝒓−𝒍𝒂𝒄) 𝑰 𝒑𝒚𝒓,𝒑𝒉𝒂𝒔𝒆𝒅 = 𝑰 𝒑𝒚𝒓,𝒅𝒚𝒏 𝒆−𝒊∡𝑨𝑼𝑪 𝒑𝒚𝒓 𝑰 𝒃𝒊𝒄,𝒑𝒉𝒂𝒔𝒆𝒅 = 𝑰 𝒃𝒊𝒄,𝒅𝒚𝒏 𝒆−𝒊∡𝑨𝑼𝑪 𝒃𝒊𝒄 % phase difference between pyr and lactate % directly phase pyruvate (highest SNR) % phase lactate relative to pyruvate % directly phase bicarbonate to avoid flow % affects from blood % assume no temporal change in phase
  • 9. Regions of Interest NORMAL-APPEARING WHITE MATTER PUTATIVE TUMOR: T2 LESIONT2LWM REGIONS OF INTEREST Normal-appearing white matter (NAWM) T2 Lesion (T2L)
  • 10. Kinetic traces and fitting: NAWM 4 3 0 Post-injection time (s) 10 20 30 40 50 60 0 White matter traces 0 1 2 5 6 HP-13Csignal(AU)
  • 11. kPL& kPB Maps with ROIs 0.03 0.015 0 kPL(s-1) 0.0104 0.0052 kPB(s-1) 0 White matter traces 6 ) [7] Crane et al, SIVIC visualization
  • 12. Healthy Control 0 kPL(s-1)kPB(s-1) 0.028 0.014 0 0.0078 0.0039 B A 0.022 32ch Test / Re-Test kPL,NAWM : 0.017 ± 0.001 / 0.017 ± 0.002 s-1
  • 13. Test 30-min Re-Test: Healthy Control0 kP B kPL(s-1) 0.022 0.011 0 Re-Test:24chTest:32ch Test / Re-Test kPL,NAWM : 0.017 ± 0.001 / 0.017 ± 0.002 s-1
  • 14. Serial HP Data 0.036+ kPL(s-1) 0.018 0 0.009 0.027 TP8+bevTP7+bevTP5TP6 0 10 20 30 40 50 0 10 20 30 40 50 Time (s) Time (s) 2000 4000 6000 8000 10000 2000 1000 3000 HP-13CSignal(AU) Pyruvate Lactate Bicarbonate Post-bevacizumabPre-bevacizumab Recirculation Normal-appearing white matter Patient with glioma before and during treatment with anti- angiogenic agent bevacizumab