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SIMULTANEOUS MAPPING
OF T2
* AND MAJOR
NEUROTRANSMITTERS
USING MRSI AT 3T
FATIMAH ALMOMEN1 , PINGYU XIA1 , XIAOPENG ZHOU1 , MARK CHIEW2, ADAM STEEL3 , ALBERT THOMAS4, ULRIKE DYDAK1, UZAY E EMIR1
1PURDUE UNIVERSITY, WEST LAFAYETTE, IN, 2OXFORD UNIVERSITY, OXFORD, OXFORD, 3DARTMOUTH COLLEGE, HANOVER, NH, 4DAVID GEFFEN SCHOOL OF MEDICINE AT UCLA, LOS ANGELES, CA
EMAIL: UEMIR@PURDUE.EDU
NEUROTRANSMITTERS
AND NEUROVASCULAR
COUPLING
• Gamma-aminobutyric acid (GABA)
and glutamate (Glu) are the brain's
primary inhibitory (I) and
excitatory (E) neurotransmitters.
• They are both strongly implicated
in functional changes in neural
circuitry
• Neurotransmitters: Glutamate and
GABA cause neurons and
astrocytes to activate a chain of
intracellular events, involving the
control of constriction and dilation
of the blood vessels BOLD
response
BOLD EFFECT , T2
* CHANGE
AND NEUROCHEMICALS
• Percent signal changes during activation
compared to baseline due to the BOLD signal
changes at 3 T (Δ%T2
* = 5.4 ± 1.4)
• At longer echo time (TE = 68 ms, GABA
sensitive echo time), change in T2*
exacerbates and results in signal alterations
of neurotransmitters due to the BOLD effect.
Zhu, X.-H. and Chen, W. (2001),
Monitoring T2
* while measuring
neurochemicals/neurotransmitters is
essential.
Difference Difference
• SIMULTANEOUS MEASUREMENT T2
*
WITH NEUROTRANSMITTER MAPS
MIGHT PROVIDE USEFUL
INFORMATION ON FUNCTIONAL
HEMODYNAMIC CHANGES DUE
PHYSIOLOGICAL INTERVENTIONS.
• We propose using a MEGA-semi-LASER sequence
with non-water suppressed metabolite-cycling as
2D MRSI data acquisition method at 3T for high-
resolution GABA, Glutamate and T2
*detection
throughout a whole axial slice.
METHODS
• Four healthy volunteers (28.8 ±3.4 years) participated.
• MRSI scans were performed on Siemens Prisma 3T whole body MRI
scanner with
• MEGA semi-LASER localization (TR = 1 s, TE = 68 ms, number of
averages, Navg = 2, 512 s)
• The 2D polar k‐space data results in a nominal voxel of 7.5 x 7.5 x 20
mm3 (1.125 mL) Chiew, NMR in Biomed, 2017.
• MRSI spectra and Metabolite maps were stored in
NIFTI format
• FSL/FSLeyes(FMRIB, Oxford University) to
visualize/process metabolite maps
• LCModel with internal water reference.
• Unsuppressed water signals were used to generate
T2* maps using TEDANA tool, TE-dependent
analysis of multi-echo functional magnetic
resonance imaging,
The use of FSL and NIFTI for MRSI
spectra and metabolite maps
PHANTOM MEASUREMENT (NOMINAL VOXEL OF
7.5 X 7.5 X 15 mm3)
Two spheres with GABA concentrations of 1 umol/g and 2 umol/g
1
1.5
2
2.5
3
2 umol/g
1 umol/g
MEGA semi-LASER localization (TR = 1 s, TE = 68 ms,
number of averages, Navg = 2, 512 s)
GABA GABA GABA
Chiew, NMR in Biomed, 2018
MEGA-SLASER WITH METABOLITE
CYCLING TO MEASURE
NEUROTRANSMITTERS AND T2
*
RELAXATION
• Voxel-vise frequency, phase
and eddy current correction
• Significantly reduces
sideband artifact
• Rigid body Motion Correction
• Multi-echo information can
be used T2
* mapping
Chiew, NMR in Biomed, 2017
ECHO TIME-DEPENDENT ANALYSIS OF MULTI-ECHO
MAGNETIC RESONANCE SPECTROSCOPIC IMAGING
20ms 100ms
T2
* [ms]
0 0.2 0.4 0.6 0.8 1
Gray/(Gray_White)
40
50
60
70
80
90
100
110
120
T2*
[ms]
R Value = 0.59
0 0.2 0.4 0.6 0.8 1
Gray/(Gray+White)
60
70
80
90
100
110
120
T2*[ms]
R Value = 0.59
0 0.2 0.4 0.6 0.8 1
Gray/(Gray+White)
40
50
60
70
80
90
100
110
120
T2*
[ms]
R Value = 0.65
0 0.2 0.4 0.6 0.8 1
Gray/(Gray+White)
50
60
70
80
90
100
110
120
T2*[ms]
R Value = 0.40
100 150 200 250 300 350 400 450 500
[s]
54
56
58
60
62
64
66
T2*
[ms]
100 150 200 250 300 350 400 450 500
[s]
60
62
64
66
68
70
72
74
76
78
T2*
[ms]
100 150 200 250 300 350 400 450 500
[s]
56
58
60
62
64
66
68
70
T2*
[ms]
100 150 200 250 300 350 400 450 500
[s]
62
64
66
68
70
72
74
76
78
80
T2*[ms]
Gray Matter White Matter
GABA AND
GLUTAMATE
Chiew, NMR in Biomed, 2017
GABA, GLUTAMATE AND T2*
45 50 55 60 65 70 75 80
T2* [ms]
0
5
10
15
20
25
30
Glutamate
[umol/g]
45 50 55 60 65 70 75 80
T2* [ms]
0
1
2
3
4
5
6
GABA
[umol/g]
R value = 0.17
R value = 0.26
CONCLUSION
• A sequence that generates simultaneously
• GABA+
• Glutamate+Glutamine
• T2
* within a clinically feasible acquisition time of 8.5 min with a nominal voxel
dimension of 7.5 x 7.5 x 20 mm3 at 3T.
• Simultaneous measurement T2
* maps with neurochemicals is a powerful tool to
provide useful information on PHYSIOLOGICAL INTERVENTIONS which aim TO
MANIPULATE EXCITITORY-INHIBITORY BALANCE
THANK YOU SO MUCH
Uzay E Emir, uemir@purdue.edu

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GABA editing with MEGA-SLASER Metabolite cycling to measure neurotransmitters and T2* relaxation

  • 1. SIMULTANEOUS MAPPING OF T2 * AND MAJOR NEUROTRANSMITTERS USING MRSI AT 3T FATIMAH ALMOMEN1 , PINGYU XIA1 , XIAOPENG ZHOU1 , MARK CHIEW2, ADAM STEEL3 , ALBERT THOMAS4, ULRIKE DYDAK1, UZAY E EMIR1 1PURDUE UNIVERSITY, WEST LAFAYETTE, IN, 2OXFORD UNIVERSITY, OXFORD, OXFORD, 3DARTMOUTH COLLEGE, HANOVER, NH, 4DAVID GEFFEN SCHOOL OF MEDICINE AT UCLA, LOS ANGELES, CA EMAIL: UEMIR@PURDUE.EDU
  • 2. NEUROTRANSMITTERS AND NEUROVASCULAR COUPLING • Gamma-aminobutyric acid (GABA) and glutamate (Glu) are the brain's primary inhibitory (I) and excitatory (E) neurotransmitters. • They are both strongly implicated in functional changes in neural circuitry • Neurotransmitters: Glutamate and GABA cause neurons and astrocytes to activate a chain of intracellular events, involving the control of constriction and dilation of the blood vessels BOLD response
  • 3. BOLD EFFECT , T2 * CHANGE AND NEUROCHEMICALS • Percent signal changes during activation compared to baseline due to the BOLD signal changes at 3 T (Δ%T2 * = 5.4 ± 1.4) • At longer echo time (TE = 68 ms, GABA sensitive echo time), change in T2* exacerbates and results in signal alterations of neurotransmitters due to the BOLD effect. Zhu, X.-H. and Chen, W. (2001), Monitoring T2 * while measuring neurochemicals/neurotransmitters is essential. Difference Difference
  • 4. • SIMULTANEOUS MEASUREMENT T2 * WITH NEUROTRANSMITTER MAPS MIGHT PROVIDE USEFUL INFORMATION ON FUNCTIONAL HEMODYNAMIC CHANGES DUE PHYSIOLOGICAL INTERVENTIONS. • We propose using a MEGA-semi-LASER sequence with non-water suppressed metabolite-cycling as 2D MRSI data acquisition method at 3T for high- resolution GABA, Glutamate and T2 *detection throughout a whole axial slice.
  • 5. METHODS • Four healthy volunteers (28.8 ±3.4 years) participated. • MRSI scans were performed on Siemens Prisma 3T whole body MRI scanner with • MEGA semi-LASER localization (TR = 1 s, TE = 68 ms, number of averages, Navg = 2, 512 s) • The 2D polar k‐space data results in a nominal voxel of 7.5 x 7.5 x 20 mm3 (1.125 mL) Chiew, NMR in Biomed, 2017. • MRSI spectra and Metabolite maps were stored in NIFTI format • FSL/FSLeyes(FMRIB, Oxford University) to visualize/process metabolite maps • LCModel with internal water reference. • Unsuppressed water signals were used to generate T2* maps using TEDANA tool, TE-dependent analysis of multi-echo functional magnetic resonance imaging, The use of FSL and NIFTI for MRSI spectra and metabolite maps
  • 6. PHANTOM MEASUREMENT (NOMINAL VOXEL OF 7.5 X 7.5 X 15 mm3) Two spheres with GABA concentrations of 1 umol/g and 2 umol/g 1 1.5 2 2.5 3 2 umol/g 1 umol/g MEGA semi-LASER localization (TR = 1 s, TE = 68 ms, number of averages, Navg = 2, 512 s) GABA GABA GABA Chiew, NMR in Biomed, 2018
  • 7. MEGA-SLASER WITH METABOLITE CYCLING TO MEASURE NEUROTRANSMITTERS AND T2 * RELAXATION • Voxel-vise frequency, phase and eddy current correction • Significantly reduces sideband artifact • Rigid body Motion Correction • Multi-echo information can be used T2 * mapping Chiew, NMR in Biomed, 2017
  • 8. ECHO TIME-DEPENDENT ANALYSIS OF MULTI-ECHO MAGNETIC RESONANCE SPECTROSCOPIC IMAGING 20ms 100ms T2 * [ms] 0 0.2 0.4 0.6 0.8 1 Gray/(Gray_White) 40 50 60 70 80 90 100 110 120 T2* [ms] R Value = 0.59 0 0.2 0.4 0.6 0.8 1 Gray/(Gray+White) 60 70 80 90 100 110 120 T2*[ms] R Value = 0.59 0 0.2 0.4 0.6 0.8 1 Gray/(Gray+White) 40 50 60 70 80 90 100 110 120 T2* [ms] R Value = 0.65 0 0.2 0.4 0.6 0.8 1 Gray/(Gray+White) 50 60 70 80 90 100 110 120 T2*[ms] R Value = 0.40 100 150 200 250 300 350 400 450 500 [s] 54 56 58 60 62 64 66 T2* [ms] 100 150 200 250 300 350 400 450 500 [s] 60 62 64 66 68 70 72 74 76 78 T2* [ms] 100 150 200 250 300 350 400 450 500 [s] 56 58 60 62 64 66 68 70 T2* [ms] 100 150 200 250 300 350 400 450 500 [s] 62 64 66 68 70 72 74 76 78 80 T2*[ms] Gray Matter White Matter
  • 10. GABA, GLUTAMATE AND T2* 45 50 55 60 65 70 75 80 T2* [ms] 0 5 10 15 20 25 30 Glutamate [umol/g] 45 50 55 60 65 70 75 80 T2* [ms] 0 1 2 3 4 5 6 GABA [umol/g] R value = 0.17 R value = 0.26
  • 11. CONCLUSION • A sequence that generates simultaneously • GABA+ • Glutamate+Glutamine • T2 * within a clinically feasible acquisition time of 8.5 min with a nominal voxel dimension of 7.5 x 7.5 x 20 mm3 at 3T. • Simultaneous measurement T2 * maps with neurochemicals is a powerful tool to provide useful information on PHYSIOLOGICAL INTERVENTIONS which aim TO MANIPULATE EXCITITORY-INHIBITORY BALANCE
  • 12. THANK YOU SO MUCH Uzay E Emir, uemir@purdue.edu