Quantum Technology & Neurotechnology Innovation Networks: Quantum magnetic sensors for brain imaging
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Quantum Technology & Neurotechnology Innovation Networks: Quantum magnetic sensors for brain imaging
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Quantum Technology & Neurotechnology Innovation Networks: Quantum magnetic sensors for brain imaging
- 1. Connecting for Positive Change KTN connects ideas, people and communities to drive innovation that changes lives.
- 2. www.ktn-uk.org Bob Cockshott Quantum Technology Innovation Network Charlie Winkworth-Smith Neurotechnology Innovation Network Gabriela Juarez-Martinez KTN Healthcare Team Quantum Magnetic Sensors for Brain Imaging 12 November 2020 10:00 – 12:00
- 3. • 10:00 Welcome & housekeeping, Bob Cockshott & Charlie Winkworth-Smith • 10:05 Quantum magnetic sensors, Prof Matt Brookes • 10:30 SERF Magnetometry for MEG, Dr Carolyn O’Dwyer • 10:55 Clinical challenges in MEG applications, Prof Stefano Seri • 11:20 Panel Q&A • 11:50 Closing remarks Agenda
- 4. Delegates will be muted during the presentations Please use the Q & A box to post questions for the Q & A session Please only use the chat box for technical issues Housekeeping
- 5. Quantum sensing the brain Prof. Matt Brookes
- 6. Major Challenges 1 in 4 people will suffer from a mental health disorder at some point in their lifetime. However little is known about the neural substrates that underlie serious mental health conditions and there are often no effective treatments In 2015, ~29,800,000 were suffering with Alzheimer’s disease In an aging population, prevalence of dementia is growing markedly Yet again little is known about the neural substrates that underlie neurodegeneration, and treatments are lacking We know relatively little of how the brain changes in order to support cognition as we grow up, or how it declines in old age
- 7. Major Challenges Around 60 million people worldwide suffer from epilepsy, a severe neurological disorder which results from abnormal electrical activity in the brain. Epilepsy is extremely debilitating with patients suffering seizures; only 60% of cases are well controlled with pharmacological intervention Over 100,000 people in the UK are admitted to hospital per year with mild traumatic brain injury (mTBI). >50% will develop post concussion symptoms but there are no objective assessments for diagnosis Around 1 in every 100 people suffers from schizophrenia – a severe and debilitating mental health disorder which results in impaired expression and perception of reality Many of the ‘negative’ symptoms of schizophrenia are poorly controlled by drugs leading to impaired quality of life
- 8. Major Challenges Understanding the human brain, and treating brain disorders, is one of the biggest challenges for 21st century science
- 9. Brain Imaging Brain imaging has proved a remarkably successfully means to understand the brain and diagnose illnesses e.g. Modern MRI scanners, particularly ultra high field, offer structural scans with high resolution. The drive to higher field offers even further advantages. However… • Most brain imaging techniques measure the structure of the brain • Often, in mental health disorders, brain structure is normal and it is abnormal activity of neuronal assemblies that underlies many
- 10. Basic Principle Magnetoencephalography (MEG) Measure the magnetic fields generated by current flow in the human brain
- 11. Basic Principle ( ) ( ) )(,Qˆ tt T BrWr = ( ) ( ) ( ) ( )[ ]11 1 -- - = rLCrL CrL rW T T Reconstruction of MEG data relies on mathematical projection of extra-cranial magnetic fields into source space ( ) ( ) ( ) IrLrWQrW =ú û ù ê ë é ÷ ø ö ç è æ T ts ..ˆmin 2 e MAGNETIC FIELDS INFERRED CURRENT Possible to get images of current density change when a person undertakes a task SOURCE LOCALISATION
- 12. The vision
- 13. OPM-MEG
- 14. Optically pumped magnetometers Optical pumping Preparation Interaction Detection K, Rb, Cs
- 15. OPM-MEG development – 2015 – 2020 A new generation of quantum sensors have enabled ‘wearable’ brain imaging technology On scalp MEG simulations 2016 Single channel recording 2017 First wearable OPM array 2018 First paediatric helmet 2019 First Gen II OPM recordings 2019 50 channel whole head system 2020 Conventional MEG First VR-MEG recording 2019 First simultaneous OPM/EEG 2019
- 18. Natural head movement Experiment: • 10 s bouncing ball • 10 s rest bat on knee • repeated 29 times 20 s 10 s restping pong Boto et al, Nature 2018
- 19. Paedriatic OPM-MEG – Measurements in children -100 100 24 year old 10 70 Time (s)0 5 -100 5 year old 10 70 Time (s)0 5 100 -100 2 year old 10 70 Time (s)0 5 100 Images shown with written permission Hill et al. Nature Coms, 2019
- 20. Next generation neuroscience Traditional neuroimaging employs paradigms that typically comprise 2D visual projection on a screen It is hard to generate a fully immersive environment in which subjects can experience “life like” scenarios The use of Virtual Reality stimulation with neuroimaging could revolutionise the types of experiment that are possible Roberts et al. NeuroImage 2019
- 21. Outperforming competitive technology Concurrent EEG/OPM-MEG Boto et al. NeuroImage, 2019 StationaryMovingMoving more OPM-MEG EEGEEG ~10 times more sensitive to muscle artifact than MEG EEG poor spatial resolution EEG OPM-MEG
- 22. Outperforming competitive technology • Play 5 chords on a Ukulele • Measure brain activity as people learn to play the chords • Look for changes when subjects get the chords right/wrong Poorly played chords Correctly played chords
- 23. Unprecedented potential • Quantum sensors can get closer to the brain than conventional cryogenic sensors, meaning higher sensitivity and better spatial precision • Flexibility of sensor placement allows a quantum enabled system to adapt to any head shape. This means we can scan anyone - babies and adults with optimal sensor placement. • Wearability of the system means that the sensors move with the head and so, assuming background fields are controlled, we can scan people whilst they are moving. • Conventional scanners are extremely expensive to buy and run. Even at this early stage of development a quantum enabled system is <50% of the cost of a conventional system.
- 24. Unprecedented potential Epilepsy Traumatic Brain Injury AutismDementia Schizophrenia Depression Motor Neurone Disease Stroke rehabilitation Alzheimer’s disease Parkinson’s Bipolar disorderNeurodevelopment ADHD Locked in syndrome Multiple Sclerosis Suicidal thoughts Stress Covid-19 Dyslexia
- 25. Acknowledgements Richard Bowtell Peter Morris Karen Mullinger Elena Boto Lauren Gascoyne Lucrezia Liuzzi James Leggett Niall Holmes Gillian Roberts Ryan Hill Zelekha Abid Molly Rea Izzy Gale Mark Fromhold Mike Packer COLLEAGUES AND COLLABORATORS Gareth Barnes Tim Tierney Leo Duque-Munoz Eleanor Maguire Sven Bestmann Sofie Meyer George O’Neill Mark Woolrich Rebeccah Slater Caroline Hartley Andrew Quinn Margot Taylor Ben Dunkley Ben Hunt Vishal Shah James Osbourne Paul Furlong Klaus Kessler Mike Hall Nic Alexander
- 26. Thank you
- 27. Zero-Field Optically Pumped Magnetometers for Brain Imaging Carolyn O’Dwyer Experimental Quantum Optics and Photonics Group University of Strathclyde 1
- 28. Sensing and Metrology • UK-wide network of quantum technology research • Sensing and Metrology Hub @ EQOP Strathclyde • Applications-driven approach 2
- 30. Field Amplitude 1 T1 mT1 μT1 nT1 pT1 fT 100 fT 10 pT 5 mT 1 T 50 μT 250 nT 4
- 31. Field Amplitude 1 T1 mT1 μT1 nT1 pT1 fT 100 fT 10 pT 5 mT 1 T 50 μT 250 nT 5
- 32. Magnetometry Applications UnshieldedShielded Healthcare • Veterinary MCG • Clinical triage by MCG • Magnetoencephalography Security • UXO detection • Maritime defence • Nuclear threat reduction • GPS-denied navigation Geophysical • Portable survey instruments • Low-drift base station & calibration devices • Directional drilling 6
- 35. Optically Pumped Magnetometer for MEG: Specifications • Sensitive • Compact & low standoff • Scalable to arrays • Low temperature • Low cost 9
- 36. Why Use Atoms? • Every atom of an isotope is exactly the same • Alkali atoms are hydrogen-like - simple and predictable • Easily manipulated using lasers • Ultra-precise measurements 10
- 37. • Pump atomic ensemble & create magnetisation • Atoms precess about magnetic field at Larmor frequency • Precession imprinted on probe beam • ωLarmor = γB0 B0 ωLarmor Optically Pumped Magnetometry 11
- 38. • Shielded or compensated room creates a quiet environment for sensor • Sensor has a response at zero- field • Any signal arising shifts the Larmor frequency Zero-Field Magnetometry 12 Amplitude Magnetic Field 0
- 39. • Shielded or compensated room creates a quiet environment for sensor • Sensor has a response at zero- field • Any signal arising shifts the Larmor frequency Zero-Field Magnetometry 13 Amplitude Magnetic Field 0
- 40. Compact Magnetometer 14 ~20 mm Laser Atomic Vapour Cell Low-noise heating Detection
- 41. Compact Magnetometer 15 Key Build Components • Laser • Atomic Vapour Cell • Low-noise heating • Detection VCSEL laser with TEC control & feedback
- 42. Compact Magnetometer Standard 1.5 mm Cs-N2 cell Double-pass 5 mm cells in variety of geometries 16 Key Build Components • Laser • Atomic Vapour Cell • Low-noise heating • Detection
- 43. Compact Magnetometer 17 Key Build Components • Laser • Atomic Vapour Cell • Low-noise heating • Detection Self-balancing two-channel photodetector Cell heater & thermocouple readout
- 44. Scalability 18
- 45. Scalability 19
- 47. Challenges • Heating: ~110℃ at cell, ~30℃ at scalp • Laser supply chain - tunable and stable packages • Optimisation of vapour cell fill pressure and geometry • Two-cell operation - gradiometry 21
- 48. Progress & Outlook • Lab experiment complete • Optimisation and calibration ongoing • Sensitivity estimate - compare to current available sensors • Portable component testing in lab environment 22 -1000 -500 0 500 1000 Magnetic Field (nT) 0.1 0.11 0.12 0.13 0.14 0.15 0.16 SignalAmplitude(V)
- 49. SERF Magnetometry Team Erling Riis Paul Griffin Stuart Ingleby Terry Dyer Iain Chalmers Rachel Dawson Edward Irwin Marcin Mrozowski 23
- 50. Clinical challenges in MEG applications Stefano Seri MD, PhD, FRCP Wellcome Laboratory for MEG Studies, Aston Univesity Birmingham Women’s and Children’s NHS FT CESS Programme
- 51. The puzzling dichotomy • Continuous growth in the number of publications: in the first 9 months of 2020 alone: • Epilepsy 80 studies • Schizophrenia 20 studies • Mood disorders 17 studies • Autism 16 studies • Dementia 14 studies • Other neuro-degenerative conditions 10 studies • TBI 7 studies • Publication of the world’s first set of clinical MEG Clinical Practice Guidelines (CPGs)
- 52. The puzzling dichotomy: on-going challenges • ‘‘Existing disparities in the current practice of clinical MEG in the United States necessitate clinical practice guidelines” (Bagic, 2011) • Need to Identify ‘‘a basis to harmonize clinical MEG procedures” (De Tiège et al., 2017) • Symposium ‘‘Quo Vadis Clinical MEG Worldwide?” (31st ICCN in Washington DC May 6, 2018)
- 53. European clinical centres survey • 12 clinical European MEG centres included in this study • 10 (83%) reported to use MEG for pre-surgical functional mapping (median number of investigations 25, total: 244)
- 54. On-going operational challenges 1. Unfavourable economics of SQUID-based systems (tariff for insurance reimbursement in USA up to USD 10.000 per test) 2. Relatively low penetrance to clinical routine 3. Evident lack of standardization in procedures, which limits large scale studies (meta-analyses) and complicates training of clinical scientific staff 4. Lack of clinically driven design of user interface and pipelines of existing systems 5. Reliance of open-source software with no clinical validation
- 55. Specific challenges with paediatric age
- 56. Photographs reproduced with parental consent CTF Omega 275 Sensor ELEKTA Triux 306 sensor
- 57. Photographs reproduced with parental consent Challenges of recording children
- 58. Effect of head size on shoulder-crown distance Courtesy K.D. Singh CUBRIC, Cardiff University, UK
- 59. 5% and 95% confidence intervals, for children aged 2-12. The red dotted line indicates the depth of the Dewar helmet; children with a shoulder-crown distance below this line would not be fully inserted into the helmet. Green triangles indicate the shoulder- crown distance of some of our patients from the BCH Epilepsy Surgery Programme: children as old as 10+ years fall below the red line. Mean shoulder-crown distance
- 61. The total mean distance (left plus right), with 5 and 95% confidence intervals, between a child’s temples and the helmet sides. At age 2, the temporal lobes are 2-3 cm further from the MEG sensors than at age 16; 1 cm is equivalent to a 5-fold increase in SNR . Head distance from dewar with age
- 62. MEG in epilepsy
- 63. Clinical MEG at Aston in 9 steps ü Referral and screening form (metal, implantable devices) ü On arrival, clinician integrates referral with further history ü Removal of metallic objects ü Explanation regarding protocols (spontaneous activity, mapping eloquent cortex, sleep …), offer to view video on screen ü Data acquisition (high sampling rate) ü MRI MPRAGE on 3T Siemens Trio for co-registration ü Review sensor-space data for IEA and spatial filtering data: analysis by post doctoral staff ü Team discussion on VE time-series and corresponding sensor space data ü Report prepared by Consultant and posted to referring team
- 64. Localising data in the time domain 1. Statistical or visual identification of abnormal transients with coherent topography (IEDs) 2. Single vs. averaged IEDs 3. Localising sources of abnormal activity
- 65. Towards automated IEDs identification: excess kurtosis
- 66. Pt. E.S. 15 years old, EPC involving left lower limb SAM(g2) irritative zone localisation
- 67. 1. Left Temp Dysplastic Lesion 2. Seizures characterised by epigastric subjective sensation, staring chewing automatisms LMN, DOB: 24/12/02
- 70. Peak01 Peak02
- 73. Recording seizures with MEG
- 74. Patient VZ, FCD, age 16
- 75. Cortical Dysplasia A B C D “Magnetographic” Seizure Progression
- 76. So far, for the 482 referrals 77/482 (16%) patients did not show any IEAs Of the 405 who showed abnormalities 307 (75.8%) patients showed at least one source within the epileptogenic lesion 98 (24.2%) patients have had intraoperative verification Of these 98 patients 73 (74.5%) had at least one identified source within the context of the resected area and Engel’s class I outcome 17 (17.4%) had sources concordant at lobar level 8 (8.1%) had sources in a different lobe
- 78. Final considerations: current challenges § Large datasets vs short epochs: long processing time § Historically sensitive to excessive movement: limits use in ictal recordings. § Not feasible at patient’s bedside (limiting for ictal and for prolonged recordings) § Sensitivity to the distance of sources from sensor (helmet design/ software optimisation for paediatric age) § Relatively insensitive to radial sources ? In clinical practice virtually immaterial § High frequency oscillations are powerful biomarkers of epileptic zone: SNR of current and future technology at 250-500 Hz ?
- 79. Practical Implications 1. Visual Inspection: will it still be necessary ? 2. Which department does the technique belong to? 3. Training a new generation of HCS 4. Is there a role for high density MEG in signal space?