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Connecting for Positive Change
KTN connects ideas, people and
communities to drive innovation that
changes lives.
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
• 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
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
Quantum
sensing the
brain
Prof. Matt Brookes
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
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
Major Challenges
Understanding the human
brain, and treating brain
disorders, is one of the
biggest challenges for 21st
century science
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
Basic Principle
Magnetoencephalography (MEG)
Measure the magnetic fields generated by
current flow in the human brain
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
The vision
OPM-MEG
Optically pumped magnetometers
Optical pumping
Preparation Interaction Detection
K, Rb, Cs
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
OPM-MEG system overview
Example
measurements
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
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
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
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
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
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.
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
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
Thank you
Zero-Field Optically Pumped
Magnetometers for Brain Imaging
Carolyn O’Dwyer
Experimental Quantum Optics and Photonics Group
University of Strathclyde
1
Sensing and Metrology
• UK-wide network of quantum
technology research
• Sensing and Metrology Hub @
EQOP Strathclyde
• Applications-driven approach
2
Making Measurements
3
Field Amplitude
1 T1 mT1 μT1 nT1 pT1 fT
100 fT
10 pT 5 mT
1 T
50 μT
250 nT
4
Field Amplitude
1 T1 mT1 μT1 nT1 pT1 fT
100 fT
10 pT 5 mT
1 T
50 μT
250 nT
5
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
Hall Sensors
Current Technologies
Sensitivity
Size
SQUID
Fluxgate
7
Hall Sensors
Current Technologies
Sensitivity
Size
SQUID
Fluxgate
OPM
8
Optically Pumped Magnetometer for MEG:
Specifications
• Sensitive
• Compact & low standoff
• Scalable to arrays
• Low temperature
• Low cost
9
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
• 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
• 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
• 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
Compact Magnetometer
14
~20 mm
Laser
Atomic Vapour Cell
Low-noise heating
Detection
Compact Magnetometer
15
Key Build Components
• Laser
• Atomic Vapour Cell
• Low-noise heating
• Detection
VCSEL laser with
TEC control
& feedback
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
Compact Magnetometer
17
Key Build Components
• Laser
• Atomic Vapour Cell
• Low-noise heating
• Detection Self-balancing
two-channel
photodetector
Cell heater &
thermocouple
readout
Scalability
18
Scalability
19
Scalability
20
FPGA
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
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)
SERF Magnetometry Team
Erling Riis
Paul Griffin
Stuart Ingleby
Terry Dyer
Iain Chalmers
Rachel Dawson
Edward Irwin
Marcin Mrozowski
23
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
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)
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)
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)
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
Specific challenges with paediatric age
Photographs reproduced with parental consent
CTF Omega 275 Sensor ELEKTA Triux 306 sensor
Photographs reproduced with parental consent
Challenges of recording children
Effect of head size on shoulder-crown
distance
Courtesy K.D. Singh
CUBRIC, Cardiff University, UK
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
Movement
minimisation
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
MEG in epilepsy
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
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
Towards automated IEDs identification: excess kurtosis
Pt. E.S. 15 years old, EPC involving left lower limb
SAM(g2) irritative zone localisation
1. Left Temp Dysplastic Lesion
2. Seizures characterised by
epigastric subjective
sensation, staring chewing
automatisms
LMN, DOB: 24/12/02
LEFT
RIGHT
LMN, DOB: 24/12/02
LMN, DOB: 24/12/02
Peak01
Peak02
Recording seizures with MEG
Patient VZ, FCD, age 16
Cortical
Dysplasia
A B
C D
“Magnetographic” Seizure Progression
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
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 ?
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?

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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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 71.
  • 72.
  • 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
  • 77.
  • 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?