UTE MRSI MRI IDH 2-hg zoom MRSI

1. HIGH FIELD
MRI METHODS
TO STUDY
HUMAN BODY
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. COMPARATIVE
HISTORY
• Comparative history is the comparison of
different societies which existed during
the same time period.
• Automobile Society
• Smartphone Society
• 1H MRS @high field

5. AUTOMOBILE SOCIETY
• 2001
…
• 2012

6. SMARTPHONE SOCIETY
• 2001
…
• 2012

7. 2001 NAA
Glu
Asp
NAA
Gln
Cr
PCr
Ins
Tau
Cr
PCr
Gln
Glu
Ins
H2O
Glc
NT = 64
STEAM
TE = 6 ms TR = 5 s
VOI = 2 x 2 x 2 cm3
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5 ppm
5.0
5.5
6.0
Tkáč, MRM,2001
NMR spectra were obtained from
phosphate containing metabolites
in early 70s
Metabolomics ?

8. “Violent hierarchy”
"IT’S UNFAIR TO BLAME THE TOOL.
IT’S LIKE BLAMING A TELESCOPE WHEN SOMEBODY’S WRONG ABOUT [IDENTIFYING] A PLANET.
IT’S NOT THE TELESCOPE’S FAULT.” Rebecca Saxe at MIT
“There are questions … is good at answering and questions it is bad at answering.
There are right ways to use …., and there are irresponsible ways to use it.” Brian Resnick @B_resnick brian@vox.com
Question Tool

9. METHODS HAS TO BE CLINICALLY PRACTICAL
• Methods has to be simple to run without requiring any
manipulation from the user
• Results have to be easy to interpret if possible during the scan
time
2012
2021
https://www.youtube.com/watch?v=QN-eLHdwClM
https://www.cmrr.umn.edu/spectro/nc-
cms/content/upload/sLASER_VDVE.pdf

10. RADIO WATER

11. RADIO CHANNELS BEYOND WATER
CH3
H2O

12. MRS OR MRI
Question Tool

13. CANCER
Question Tool

14. 2-HG and cancer metabolism
metabolic reprogramming
IDH-mutants
undergo
metabolic
reprogramming2,
3
1H-MRS (7T)
Potential to gain more integrated in
vivo information from other metabolites
(Gly, GSH, Lac, Glu, Gln)
1Kalinina et al. (2012)
3Tateishi K et al. (2015)
2Viswanath P et al. (2016)

15. SEMI-LASER FOR 2-HG DETECTION AT 3T

16. 3T
7T
Detection of 2-HG at 7T

19. 1
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
CYSTATHIONINE
-Co-deletion Co-deletion
IDH2 mutations predominantly occur in
oligodendroglial tumors
IDH2 mutations are commonly
associated with 1p/19q codeletion
Cystathionine may be a marker for
1p/19q codeleted gliomas
Branzoli, Neuro Oncol, 2019

20. The need for
Ultra-High-Field
MRS
Molecular Status
Beyond IDH
mutations
less than 5
minutes
1p/19q codeletion and
beyond

21. THE NEED FOR
ULTRA-HIGH-
FIELD MRS
A Prognostic Precision
Medicine Biomarker Detection
System
Precision medicine strategies
• Tailoring therapies,
• Delivering more effective treatments,
whilst avoiding or reducing adverse
outcomes
 Identify
 Stratifying,
 Monitoring IDH1 and IDH2 mutant
glioma patients

22. INCREASE IN SENSITIVITY
ALLOWS THE HIGHEST
RESOLUTION 2-HG MAP
AT 3T
SEMI-LASER
TE = 110 MS
VOI = 5 X 5 X 10 MM3
TA=4 MINUTES
=
SEMI-LASER
TE = 110 MS
VOI = 10 X 10 X 10 MM3
TA= 1 MINUTE

23. PSYCHOACTIVE DRUG
TRIALS (EBSELEN TRIAL)
• Mood stabilizers
• classically -> Lithium
• Inositol-depletion hypothesis (Harwood, Molecular Psychiatry, 2005)
• Inhibition of the enzyme inositol-1 (or 4)-monophosphatase (IMPase)
• However, undesirable side effects
• reduced urinary concentrating ability,
• hypothyroidism, hyperparathyroidism
• Weight gain
• Novel -> ebselen
• Bioavailable antioxidant drug
• Clinical trials for cardiovascular diseases, arthritis, stroke, atherosclerosis,
and cancer (Azad et al., Mol Biol Rep, 2014)
• Inhibition of IMPase (Singh et al., Nat. Commun, 2014)

24. SPECTRAL QUALITY
7T
STEAM
TE=11ms
TR=5 s
3T
semi-LASER
TE=28 ms
TR=5 s

25. NEUROCHEMICAL PROFILES
3T
7T

26. COMBINED FMRS-FMRI

27. 7T semi-LASER
TE=36 ms
TR=5 s

28. EVENT RELATED
FMRS AND FMRI

29. POPULATION BASED STUDY
MAGNETIC RESONANCE IMAGING IN
A CROSS-SECTIONAL SAMPLE
SPANNING FROM CHILDHOOD
TO ADULTHOOD
• Cross-sectional sample spanning
from childhood to adulthood which
was reassessed in 1.5 years (N =
293).
• 3T Siemens MAGNETOM Prisma
MRI System
• Spectra were measured by semi-
adiabatic localization using an
adiabatic selective refocusing (semi-
LASER) sequence (TE = 32 ms; TR =
3.5 s; 32 averages;). Total
acquisition less than minutes
• 20 Neurochemicals were reported

30. NEUROCHEMICAL ALTERATIONS VS AGE

31. HOW ABOUT 7T

33. SV-MRS: SPINOCEREBELLAR ATAXIAS

34. SV-MRS: SPINOCEREBELLAR ATAXIAS

35. WHAT IS NEW?

36. ZOOM-MRSI
WITH
METABOLITE
CYCLING
• Emir, UE, Sood, J, Chiew, M, Thomas, MA, Lane, SP. Magn
Reson Med. 2021; 85: 2349– 2358.
ZOOM-MRSI

37. make good use of all the
information of acquisitions
from multiple coils
Generate different phase
modulation in different slices
MUTLI-BAND ZOOM-MRSI
https://www.biorxiv.org/content/10.1101/628594v1.full
3 ZOOM-MRSI
slices with a 62.5 μL
resolution in 4.5
minutes

38. KIDNEY ZOOM-MRSI

39. KIDNEY ZOOM-MRSI https://youtu.be/xKB-nOjcAYE

40. ZOOM-MRSI FOR
SODIUM IMAGING
• 2.5 × 2.5 × 20 mm3 (nominal resolution = 0.125 mL)
• TE = 0.55 ms
• total acquisition time (TA) of 15 min and 24 s.
Alhulail, AA, Xia, P, Shen, X, et al. Magn Reson Med. 2021; 85: 1783– 1794.

41. STUDYING THE CHEMICAL
COMPOSITION OF THE HEARTH
Work in Progress
FID,TE=4ms, 0.25 mL, 3.2 min,
free breathing, no cardiac
gating

42. MULTI-ECHO MRI FOR UTE IMAGING
• A nominal resolution of 2 mm3 isotropic
• TE=30 us
• FOV =240 mm3 isotropic
• TR = 7ms
• FA= 8
• total 20 echo times
• Total Acquisition = 10 minutes , af=4

43. UTE-MR(S)I
Lung Imaging 1 minute
acquisition
Sodium Cartilage Imaging

44. MRS OR MRI
Question Tool
• Methods has to be simple to run without requiring any
manipulation from the user
• Results have to be easy to interpret if possible during the
scan time

45. THANK YOU SO MUCH
Purdue
• Ulrike Dydak
• Sean Lane
• Xin Shen
• Nicholas Farley
• Pingyu Xia
• Ahmad Al-Hulail
UCLA
• Albert Thomas
MGH
• Matthew Rosen
• Neha Koonjoo
UNIVERSITÄTSKLINIKUM FREIBURG
• Ali Caglar Ozen
The study was supported by the Indiana CTSI and
funded in part by grant #UL1TR001108 from the the
National Institutes of Health (NIH), National Center for
Advancing Translational Sciences (NCATS) Clinical
and Translational Science Awards (CTSA)
Showalter Trust Purdue MRI Facility