Magnetic Resonance Spectroscopy, MRI, Human Connectome, 2-HG, 2-hydroxyglutarate, zoom, zoom MRSI, reduced field of View, rFOV, Cerebellum, High-resolution, IDH, Isocitrate, IDH1, IDH2, Cancer, Glioma, Parcellation, Macro Anatomical Functional Myeloarchitectonic CYTO- AND RECEPTOR ARCHITECTONIC MAPPING OF THE HUMAN BRAIN MR Spectroscopy Study Group

1. MRS AND METABOLOMICS
SCHOOL OF HEALTH SCIENCES AND WELDON SCHOOL OF BIOMEDICAL ENGINEERING
PURDUE UNIVERSITY, WEST LAFAYETTE, IN, UNITED STATES
UEMIR@PURDUE.EDU

2. PERSONALIZED
MEDICINE
Saykin et al, Alzheimers Dement. 2015 Jul;11(7):792-814.

3. MULTI-OMICS ERA
• NMR spectra were obtained from
phosphate containing metabolites in
early 70s
• Metabolomics ?
• The fMRI, a newbie compared to
MRS, has evolved in practice,
sophistication, range of applications,
and impacts.
• Notably, it has been playing a
pivotal role in human brain
mapping, one of the significant
scientific challenges of the 21st
century.
• Connectomics
Saykin et al, Alzheimers Dement. 2015 Jul;11(7):792-814.

4. BARRIERS OR NOT BARRIERS
MRI/fMRI
• Acquisition
• Processing
• Applications
MRS
• Acquisition
• Processing
• Applications

5. IS THE
TERMINOLOGY A
BARRIER?
MRS AND MRI
MRS Multi-Echo
MRI
Any efforts improving MRI
improve MRS
Acquisition, Processing, Application

6. SCALING UP THE SIZE OF THE COLLABORATIONS FOR
THE POPULATION-BASED STUDIES

7. MOLECULAR IMAGING VIA MRS
SHOULD NOT BE THE
SATELLITE/SUPPORTING
MODALITY,
IT SHOULD BE THE
ULTIMATE GOAL

8. STUDYING THE CHEMICAL
COMPOSITION
•MRS enables us to study Metabolic
Processes Related to:
• Development & Function
• Disorders
• Metabolomics of Cancer
• Energy Metabolism
• Lipidomics (Lipid
accumulation)

9. TARGETED METABOLOMICS/
MOLCECULAR PROBING OF THE HUMAN ORGANS
Hardware
• Increased Magnetic Field
• Improved Gradients
• Improved Coils Transmit/Receive
Coils
• Improved Shim Coils
• …
Pulse Sequence
• Improved Localization
• Semi-LASER, LASER,
SPECIAL
• FID-acquisition for
accelerated MRSI
• Improved Water Suppression
techniques
• Efficient spatial encoding
trajectories for MRSI
• …
Post Processing
Open Source processing
• FSL-MRS
• OSPREY
• VESPA
• JMRUI
• Tarquin
• FID-A
• SIVIC
SPECIAL ISSUE REVIEW ARTICLES NMR in
Biomedicine 2020

10. IS THE DATA FORMAT A BARRIER?
WHY NOT NIFTI?
https://www.biorxiv.org/content/10.1101/2020.06.16.155291v1.full
https://forum.mrshub.org/t/bids-for-spectroscopy/83

11. THE POPULATION-
BASED STUDIES:
SAMPLE SIZE
MATTERS
• MRS methodologies are mature enough for
a Human Metabolomics
• Healthy
• Disease
• Metabolome is not limited to Central Nervous
System
• Metabolome is not limited to 1H
SPECIAL ISSUE REVIEW ARTICLES NMR in
Biomedicine 2020

12. HUMAN BRAIN
METABOLOMICS
• Whole Brain via MRSI
• Parcellated approaches via SVS and/or Zoom MRSI
• Macro Anatomical
• Functional
• Myeloarchitectonic
• …

13. PARCELLATED APPROACH VIA ZOOM MRSI
CEREBELLUM
• Short echo-time (TE) semi-LASER MRSI at 3T with a nominal resolution of 62.5 μL

14. METABOLITE
DISTRIBUTIONS IN THE
CEREBELLUM
• The molecular imaging of the cerebellum can
contribute to understanding the
cytoarchitecture of the cerebellum in
addition to the functional and macro
anatomical mapping.
• Quantitative in vitro receptor
autoradiography studies demonstrated the
regional distribution of receptor-bindings in
the cerebellum
• This approach can be applied to other
organs
NAA
Glx
N. PALOMERO-GALLAGHER AND K. ZILLES, CYTO- AND RECEPTOR ARCHITECTONIC MAPPING OF THE HUMAN BRAIN
Cr

15. HOW ABOUT THE DEEP LEARNING?
NUFFT
AUTOMAP
Center for Machine Learning Mass General/Martinos Center for Biomedical Imaging Harvard
Medical School
• Matthew Rosen
• Neha KOONJOO
• Short echo-time
(TE) semi-LASER
MRSI at 3T with a
nominal resolution
of 62.5 μL. Spectral
bandwidth 893 Hz.
The acquisition
duration is ~ 3
minutes
Cho
Cr
NAA

16. WE NEED TO SCALE UP
THE SIZE OF THE
COLLABORATIONS FOR
THE NONINVASIVE
METABOLOMICS OF
HUMAN BRAIN
(ORGANS) VIA MRS
SAMPLE SIZE MATTERS

17. DISEASE: CANCER
METABOLOMICS FOR BRAIN TUMORS

18. CANCER METABOLISM
(POST-GENOME)
IDH-mutant
80% of grade II-III gliomas + secondary
glioblastomas
(Dang et al. 2009)
q Linked to prognosis
q Sensitivity to targeted therapy
q IDH inhibitors are being developed 5 - 35 mM
2-HG

19. MRS IS THE ONLY NON-INVASIVE IMAGING MODALITY
SUBTYPE GENETIC MUTATIONS
SUBCELLULAR COMPARTMENTALIZATION

20. STUDYING THE CHEMICAL SIGNATURES OF
THE LOW-GRADE GLIOMAS
7T, Semi-LASER TE=110, TR= 2-3s
3T
7T

21. RARE MUTATION
IDH2 R172W

22. 2-HG AND
ASSOCIATED
METABOLITES

23. 1p/19q codeletion, strong prognostic factor
and also a predictive factor of response to
chemotherapy
REFINEMENT OF THE BASIS SET: CYSTATHIONINE
DETECTION AT UHF (7T) MRS

24. REFINEMENT OF THE BASIS SET: CYSTATHIONINE
DETECTION AT UHF (7T) MRS
1p/19q codeletion, strong prognostic factor
and also a predictive factor of response to
chemotherapy, Cystathione in the basis set

25. REFINEMENT OF MRS BASIS SET WITH (UHF MRS 7T)

26. WE NEED TO SCALE
UP THE SIZE OF THE
COLLABORATIONS
FOR
THE NONINVASIVE
METABOLOMICS OF
GLIOMAS VIA MRS
SAMPLE SIZE
MATTERS

27. VISION

28. THANK YOU SO MUCH
Purdue
• Xin Shen
• Ahmad Al-Hulail
• MRI Facility
Utrecht University
• Jannie Wijnen
• Evita Wiegers
• Anja van der Kolk
Oxford University
• Irene Tracey
• Heidi Johansen-Berg
• Mark Chiew
• Peter Jezzard
• Natalie Voets
• Olaf Ansorge
• Puneet Plaha
• Christopher Schofield
• Thomas Cadoux-
Hudson
• James Mccullagh
Memorial Sloan Kettering
Cancer Center
• Oguz Akin
Acibadem University
• Alp DincerUCLA
• Albert Thomas
Center for Machine Learning Mass General/Martinos Center for Biomedical Imaging Harvard Medical School
• Matthew Rosen
• Neha KOONJOO