HIGH-FIELD MRS methods to Study Human Body ZOOM MRSI 2-hg 2-hydroxyglutarate IDH mutation 7 Tesla
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HIGH-FIELD MRS methods to Study Human Body ZOOM MRSI 2-hg 2-hydroxyglutarate IDH mutation 7 Tesla
- 1. Deconstructive reading of “Usefulness of MRS” (What is said and what is left unsaid) Uzay E Emir FMRIB Centre, Nuffield Department of Clinical Neurosciences, University of Oxford, UK
- 2. “Jacques Derrida was one of the most well known twentieth century philosophers.”
- 3. Deconstruction • "Deconstruction refers to all of the techniques and strategies used by Derrida in order to destabilise, crack open and displace texts that are explicitly or invisibly idealistic" (Hottois, 1998).
- 4. W A T E R Lake Water Drops MR detectable water signal A Glass of Water
- 5. Unequal pairs/Binaries “Violent hierarchy” • Masculine • Subject • Center • Past • Usefulness • Feminine • Object • Margine • Present • Useless
- 6. Unequal pairs/Binaries “Violent hierarchy” • Masculine • Black • Subject • Center • Past • Usefulness • Feminine • White • Object • Margine • Present • Useless struct is to bypass all rigid conceptual op
- 8. “Usefulness of MRS” • 31P MRS has been the first method applied to medicine in vivo
- 10. “Violent hierarchy” PE WHEN SOMEBODY’S WRONG ABOUT [IDENTIFYING] A t answering. There are right ways to use …., and there are irre Question Tool
- 12. Protons in Other Molecules
- 15. Tool
- 19. Combined fMRS-fMRI • Concurrent measurements of BOLD-fMRI and neurochemicals, at a temporal resolution compatible with human fMRI studies.
- 21. Psychoactive Drugs Trials (Bipolar Disorder (BPD)) • Bipolar disorder is among a class of mood disorders that is marked by dramatic changes in mood, energy and behaviour. • Characterised by episodes of mania and depression • Affecting 1-3 % of the world population • Key regions of the cortico-limbic network and their major network connections relevant to bipolar disorder (Brooks III et al., Journal of Psychiatric Research, 2014)
- 22. Ebselen • 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)
- 23. To monitor if ebselen reduces brain neurochemicals as compared to placebo control Assess neurochemical profile of Frontal and Occipital Cortices by short-echo 1H MRS at 3T Assess extended neurochemical profile of Frontal and Occipital Cortices by short-echo 1H MRS at 7T
- 26. Total Creatine Positively Correlated with myo-Inositol Creatine is not an adequate internal standard where subjects have been medicated with ebselen or lithium (O’Donnell et al., Brain Research, 2000)
- 27. Question Tool MRS acquisition and processing pipeline allowed us to detect a small but statistically significant decrease in myo-inositol level Justifying Utilisation of MRS in drug discovery studies
- 29. Cancer Imaging in the Post-genomic era Post-genomic era Patient stratification
- 31. IDH-mutant 80% of grade II-III gliomas + secondary glioblastomas (Dang et al. 2009)
- 32. 1H-MRS (7T) 1Kalinina et al. (2012) 3Tateishi K et al. (2015) 2Viswanath P et al. (2016) 2-HG and cancer metabolism metabolic reprogramming 5 - 35 mM
- 33. 1Kalinina et al. (2012) 3Tateishi K et al. (2015) 2Viswanath P et al. (2016) 1H-MRS (7T) Potential to gain more integrated in vivo information from other metabolites (Gly, GSH, Lac, Glu, Gln) 2-HG and cancer metabolism metabolic reprogramming
- 34. 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)
- 35. 3T 7T semi-LASER sequence (TE = 110ms) Detection of 2-HG
- 36. 2-HG Lactate Lactate Detection of 2-HG 2-HG
- 37. Semi-LASER MRSI acquisition (TE=110 ms, TR= 1.5 s, 10 averages, Total duratio Question Tool In vivo investigation of cancer metabolic reprogramming Justifying Utilisation of MRS in cancer imaging
- 38. Question Tool MRS nd questions it is bad at answering. There are right ways to us
- 39. • https://youtu.be/TNOXuurUODE Jacques Derrida “Deconstruction doesn’t produce any sitcom. If sitcom is this, and people who watch this think deconstruction is this, the only advice I have to give them is just stop watching sitcom, do your homework, and read.”
- 40. Acknowledgement s Peter Jezzard Phil Cowen Adam Berrington Betina Ip Aaron Hess Holly Bridge Charlie Stagg Beata Godlewska FMRIB Physics Group Thank you for your attention