Cutting-Edge Advances in Brain Tumor Imaging (2-hydroxyglutarate, IDH mutation Magnetic Resonance Spectroscopy Imaging) at 3 Tesla (3T) and 7 Tesla (7T) Noninvasive assessment of isocitrate dehydrogenase mutation 2-Hydroxyglutarate MR spectroscopy for prediction of isocitrate dehydrogenase mutant glioma 2-Hydroxyglutarate as a Magnetic Resonance Biomarker for Glioma Detection of oncogenic IDH mutations using magnetic resonance spectroscopy of 2-hydroxyglutarate metabolomic analysis RSNA Wellcome Centre for Integrative Neuroimaging FMRIB Purdue 2-HG IDH1 IDH2 MRS MRSI MRI ultra-high field CLINICAL ROLE OF MRS QUANTIFICATION OF 2HG IN DIAGNOSIS OF GLIOMAS Ultra-high-field MRI – Precision Medicine the clinical application of 7-Tesla imaging UHF 7T 7Tesla Semi-LASER, semilaser Slaser

1. See discussions, stats, and author profiles for this publication at: https://www.researchgate.net/publication/333189636
A Noninvasive Comparison Study between Human Gliomas with IDH1
and IDH2 Mutations by MR Spectroscopy
Conference Paper · May 2019
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Sarah Jane Larkin
University of Oxford
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2. A Noninvasive Comparison Study
between Human Gliomas with
IDH1 and IDH2 Mutations by MR
Spectroscopy
Xin Shen1, Natalie Voets2, Sarah Larkin2, Nick de
Pennington2, Puneet Plaha3, Richard Stacey3, James
Mccullagh2, Christopher Schofield2, Stuart Clare2, Peter
Jezzard2, Tom Cadoux-Hudson3, Olaf Ansorge2, and Uzay
Emir1,2,4
1Weldon School of Biomedical Engineering, Purdue University,
West Lafayette, IN, United States,
2University of Oxford, Oxford, United Kingdom,
3Oxford University Hospitals NHS Trust, Oxford, United
Kingdom,
4School of Health Sciences, Purdue University, West Lafayette,
IN, United States

3. Precision Medicine Era
Biomarker
Stratify
Patients
Monitor

4. 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. simulated 2-HG spectral pattern at 3T
5 - 35
mM
2-HG
Pope et al., Neurooncol., 2011
Choi et al., Nat Med., 2012
Andronesi et al., Sci Transl Med. ,2012
Berrington A. et al. Tomography (2016)
2-Hydroxyglutarate (2-HG) Detection at 3T

6. 2-HG detection with semi-LASER Echo
Time=110 ms (Double Spin-Echo Adiabatic
Localization)
Emir UE. et al. Cancer Research (2016)
Berrington A. et al.Tomography (2016)
Berrington A. et al. NMR Biomed (2018)
3T
7T

7. 3 Tesla
Increase in sensitivity
allows the highest
resolution 2-HG
mapping at 3T
Semi-LASER
TE = 110 ms
VOI = 5 x 5 x 10 mm3
IDH2 patient, Steel at al., Scientific Reports, volume 8, Article number: 7792 (2018)

8. Non-invasive molecular subtyping and
Subcellular compartmentalization
7T

9. Non-invasive molecular subtyping and
Subcellular compartmentalization
7T

10. • Aim: To determine whether metabolic reprogramming
associated with IDH mutant gliomas at 7T.
• A total of 21 patients (age = 37 ± 11, 13 males)
• IDH1 (n = 15) and IDH2 (n = 5) and
• No histopathological diagnosis could be established for one
glioma patient
• Nova Medical single-channel transmit and 32 channel
receive array head-coil.
• Spectra were fitted with LCModel using simulated basis
sets
• The mutation subtype (IDH1 or IDH2) was assessed by
IHC and DNA sequencing from a surgical tissue biopsy

11. Shen et al., Metabolites 2019, 9, 35.

12. IDH1 vs IDH2
Mitochondria vs Cytoplasm
Shen et al., Metabolites 2019, 9, 35.
Hypermethylation
ISYNA1
Oxidative
phosphorylation
Oxidative
phosphorylation
Oxidative
phosphorylation

13. Metabolomics of IDH1 and IDH2 using MRS
at 7 Tesla
Shen et al., Metabolites 2019, 9, 35.

14. IDH –ve (GBMs), IDH1 and IDH2
7T, semi-LASER (Double Spin-Echo Adiabatic Localization, TE = 110 ms)

15. Conclusion
The high-quality spectra of semi-
LASER (TE = 110 ms)
q Enabled the quantification of neurochemical profiles
in both IDH1 and IDH2 mutations at 7T and 3T
q Enabled the noninvasive measurement of metabolic
reprogramming associated IDH mutant brain tumors.
q Enabled the highest resolution 2-HG mapping at 3T
q Adiabatic spin-echo localization has less false
positive 2HG detection than the PRESS97 and the
MEGA68 sequence, as shown in volunteers (Abstract
#2532)
Prognostic precision medicine biomarker detection system at 3T and 7T for
identifying,
stratifying,
monitoring
IDH1 and IDH2 mutant glioma patients and beyond.
Steel at al., Scientific Reports, volume 8,
Article number: 7792 (2018)

16. Acknowledgement
• Irene Tracey, Nuffield Department of Clinical Neurosciences, University of
Oxford
• Heidi Johansen-Berg, The Wellcome Centre for Integrative Neuroimaging,
University of Oxford
• The work was supported by the NIHR Oxford Biomedical Research Centre. The Wellcome Centre for Integrative
Neuroimaging is supported by core funding from the Wellcome Trust (203139/Z/16/Z).
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