Focused Ultrasound Neuromodulation

info

registration

To register, please visit the online store.

Registration costs £120 and includes lunch, coffee/tea, social drinks, and college dinner.

All available places are currently sold out. To inquire about the waiting list, please contact funoxford2019@gmail.com.

The FUS Foundation will kindly provide funding for three poster prizes (£300, £200, £100), and one small research project prize (£1500). Please see the 'posters/awards' tab for info how to apply!

programme

Lunch and coffee/tea will be offered at Oriel college. On Monday night, we will host social drinks and college dinner for all attendees. All included in the registration. You can download the full programme or see below for a summary.

  Monday Tuesday
9.00 registration coffee
9.30 talk: Yoo talk: Monti
10.05 talk: Pauly talk: ter Haar
10.40 coffee, posters coffee, posters
11.10 talk: Treeby talk: Martin
11.45 talk: Contera talk: Aubry
12.20 talk: Verhagen talk: Folloni
12.55 lunch, posters lunch, posters
14.15 talk: Shapiro talk: Jerusalem
14.50 talk: Caskey talk: LeBlang
15.25 talk: Cleveland talk: Heimburg
16.00 coffee, posters coffee, posters
16.30 talk: Pouget talk: Legon
17.05 talk Konofagou talk: Hymynen
17.40 drinks closing
19.00 college dinner  
venue

The symposium will be held on the 23rd and 24th of September 2019 at the Harris Lecture Theatre in Oriel College. Oriel is conveniently situated on Oxford’s High Street. Its central location means that many University departments and facilities (including the Bodleian Library) are within easy reach; the shops, restaurants, and hotels of Oxford are also close by.

posters/awards

We would like to invite all attendees to present their work during the poster sessions. We would also like to encourage early-career researchers to apply for the small research proposal award (£1500).

Posters are in A0 landscape orientation and will be avaialbe for the whole duration of the symposium. Coffee, tea, and lunch are served in the poster room and we host a dedicated poster session with free drinks on Monday afternoon.

Abstract submission for posters is now open until 2nd Sept 2019. Please email them to funoxford2019@gmail.com. We encourage posters on any related research topic, so if you are new to the ultrasound field, please do feel warmly invited to present your ongoing work even if this does not include ultrasound or neuromodulation. The content of the abstract should fit on one A4 page. We prefer short abstracts with figures.

The scientific committee will review the submissions, select a set of posters for presentation, and will send a notification of acceptance. For any question with regards to submissions, please contact funoxford2019@gmail.com. Supported by the FUS Foundation we will award cash poster prizes (£300, £200, £100) to the three best posters presented at the symposium. Simply show up with a poster, and you are enrolled.

The FUS Foundation also kindly provides funding for a small research project award (£1500), with priority given to early-career researchers. This award can be used to fund any progress towards your research, for example new equipment, training costs, lab hours, conference fees, pilot scans, or travel costs. Please note, your proposal does not need to encompass a full research project, only a plan how to spend the funds benefitting your research. To apply, please prepare a brief proposal (max one A4 page) and send this to funoxford2019@gmail.com before 16th September 2019. Please include in your proposal your current job position and the (expected) date of your PhD. The scientific committee will review the proposals and select the winner.

Poster and research project prizes will be awarded during the closing session on Tuesday afternoon, 24th Sept 2019. 

mission

We will bring together researchers developing and using ultrasound stimulation as a tool for cognitive neuroscience and clinical applications. This symposium will have a strongly integrative and translational approach from mechanisms, to neural circuits, to applications, from engineering, to neuroscience, to the clinic.

Key dates
September 2, 2019 deadline for poster submission
September 9, 2019 notification of poster acceptance
September 13, 2019 deadline for registration
September 23-24, 2019 symposium

 

Oriel College, Oxford

Yes, it is sometimes sunny in Oxford. If you are lucky it may also be "warm".

travel

flight - London Heathrow

The closest airport to Oxford. An hour-ish ride on a bus will take you to Oxford city center: https://airline.oxfordbus.co.uk/heathrow/

flight - London Gatwick

Second best airport to land at, you will need to jump on a bus for another 2h30 to reach Oxford: https://airline.oxfordbus.co.uk/gatwick/

For the train afficionados or London lovers, you could also take the train to Victoria train station https://www.gatwickexpress.com/)

 

flight - other airports
Stansted

I feel sorry for you! The journey to oxford will be either a long ride on a bus (https://www.nationalexpress.com/en/destinations/oxford/stansted-to-oxford), or you will have to make a detour via London (https://www.stanstedexpress.com; there are also buses). It could be an opportunity to visit some of the many attractions of the english capital.

Luton

Not much better than Stansted I'm afraid. While it is only a 1 hour trip to Oxford if you can rent a car, the bus takes about 2.5 hours and leaves every two hours (https://www.nationalexpress.com/en/destinations/oxford/luton-to-oxford). 

Birmingham

Not too horrible, actually. Not many transatlantic flights either, but if you do catch one, you are just an hour away from Oxford by train, leaving straight from the airport (https://www.thetrainline.com/train-times/birmingham-international-to-oxford). There is also a cheaper and slower bus service (https://www.nationalexpress.com/en/airports/birmingham).

train/bus - from London

If you have arrived at St Pancras or Liverpool street station, your journey is not yet over!

Train

The average journey time between Oxford and London is 1 hour 14 minutes . The fastest journey time is 52 minutes. On an average weekday, there are 77 trains per day travelling from Oxford to London. Trains to Oxford depart from Paddington or Marylebone train stations.

https://www.thetrainline.com/train-times/oxford-to-london

Bus 

Two coach services up to every 12 minutes 24 hours a day, delivering a very reliable service for commuters: Oxford Tube and X90. These services have slightly different stops in London, but stop at the same useful places in Oxford (including very near to Oriel College). These are your cheapest options. Journey duration will be approximately 2 hours (depending on traffic).

https://www.oxfordtube.com

https://x90.oxfordbus.co.uk

accommodation

accommodation services

In Oxford, many colleges put their fellow and student accomodation up for rent outside of term time. These can be more affordable than hotels or B&Bs and can give you a taste of college life. Have a look at these services to find a room.

 

University Rooms
https://www.universityrooms.com/en-GB/city/oxford

 

Conference Oxford
http://conference-oxford.com/bb-self-catering

hotels & B&Bs

There are quite a few options for B&Bs in Oxford, all listed at the usual places: airbnb.co.uk, booking.com, etc. Here is a selection of hotels and B&Bs, in no specific order.

Oxford University Club
11 Mansfield Rd, Oxford, OX1 3SZ
http://www.club.ox.ac.uk
Rates from £104 per night
Cotswold Lodge Hotel
66a Banbury Road, Oxford, OX2 6JP
https://www.cotswoldlodgehotel.co.uk
enquiries@cotswoldlodgehotel.co.uk
tel: +44 1865 512 121
George Street Hotel
15-19 George Street, Oxford, OX1 2AB
https://www.gshoxford.co.uk
reservations@gshoxford.co.uk
tel: +44 (0)1865 957 800
Linton Lodge Hotel
11-13 Linton Road, Oxford, OX2 6UJ
http://www.bw-lintonlodgehotel.co.uk
sales@lintonlodge.com
tel: +44 (0)1865 553 461
Jury’s Inn Hotel
Godstow Rd, Oxford, OX2 8AL
https://www.jurysinns.com
tel: +44 (0)870 4100 800
Parklands B&B
100 Banbury Rd, Oxford, OX2 6JU
https://www.parklandsoxford.co.uk
stay@parklandsoxford.co.uk
tel: +44 (0)1865 554 374
St Margaret’s Hotel
41 St Margaret’s Rd, Oxford, OX2 6LD
http://www.thestmargaretshotel.co.uk
tel: +44 (0)1865 433 864
The Oxford Townhouse
90 Abingdon Road, Oxford, OX1 4PX
https://www.theoxfordtownhouse.co.uk
stay@theoxfordtownhouse.co.uk
tel: +44 (0)1865 511 122
Lonsdale Guest House
312 Banbury Road, Oxford, OX2 7ED
https://www.lonsdaleguesthouse.com
info@lonsdaleguesthouse.com
tel:+44 (0) 795 6410 489
Royal Oxford Hotel
Park End Street, Oxford, OX1 1HR
https://www.royaloxfordhotel.co.uk
info@royaloxfordhotel.co.uk
tel: +44 (0)1865 248 432
The Galaxie Hotel
180 Banbury Rd, Oxford, OX2 7BT
http://www.galaxie-booking.com
hotel@galaxie.co.uk
tel: +44 (0) 1865 515688
Holiday Inn Oxford
Peartree Roundabout, Woodstock Rd
Oxford, OX2 8JD
https://www.ihg.com/holidayinn/hotels/gb/en/oxford
tel: +44 (0) 3714 234 876

 

speakers

Central and peripheral modulation in mice and humans using focused ultrasound

Ultrasound has been consistently reported for neuronal stimulation for several decades in both animals and humans including eliciting brain activity detected by functional MRI and electroencephalography. In addition, this knowledge can be used to understand the differences between normal and pathological brains to treat patients. In the peripheral nervous system, the leading technique to treat peripheral neurological disorders is implantation of electrodes along the peripheral nerve and stimulating the nerve with electrical current. A noninvasive alternative that could treat neuropathic pain and suppress nerve activity constitutes thus an important challenge in interventional neurology.Our group has been studying the noninvasive stimulation or inhibition of both the central and peripheral nervous system in live animals. In the brain, we have shown that focused ultrasound is capable of noninvasively stimulating paw movement as well as sensory responses such as pupil dilation and eye movement when different brain regions are targeted, showing for the first time that ultrasound can trigger both motor and sensory brain responses. In the periphery, when the ultrasound beam is focused on the sciatic nerve in a live, anesthetized animal, the thigh muscle becomes activated and muscle twitches can be induced at low ultrasonic intensities while the same twitches can be inhibited at higher intensities due to associated temperature rise that inhibits nerve firing. In humans, a peripheral sensory response has also been elicited. Cellular and fiber responses in excised tissue have confirmed the live animal responses. An overview of the aforementioned findings together with the most recent results will be presented.

Elisa E. Konofagou, PhD

Elisa Konofagou

Elisa E. Konofagou is the Robert and Margaret Hariri Professor of Biomedical Engineering and Professor Radiology as well as Director of the Ultrasound and Elasticity Imaging Laboratory at Columbia University in New York City. Her main interests are in the development of novel elasticity imaging techniques and therapeutic ultrasound methods and more notably focused ultrasound in the brain for drug delivery and stimulation, myocardial elastography, electromechanical and pulse wave imaging, harmonic motion imaging with several clinical collaborations in the Columbia Presbyterian Medical Center and elsewhere. Elisa is an Elected Fellow of the American Institute of Biological and Medical Engineering, a member of the IEEE in Engineering in Medicine and Biology, IEEE in Ultrasonics, Ferroelectrics and Frequency Control Society, the Acoustical Society of America and the American Institute of Ultrasound in Medicine. She has co-authored over 200 published articles in the aforementioned fields. Prof. Konofagou is also a technical committee member of the Acoustical Society of America, the International Society of Therapeutic Ultrasound, the IEEE Engineering in Medicine and Biology conference (EMBC), the IEEE International Ultrasonics Symposium and the American Association of Physicists in Medicine (AAPM). Elisa serves as Associate Editor in the journals of IEEE Transactions in Ultrasonics, Ferroelectrics and Frequency Control, Ultrasonic Imaging and Medical Physics, and is recipient of awards such as the CAREER award by the National Science Foundation (NSF) and the Nagy award by the National Institutes of Health (NIH) as well as others by the American Heart Association, the Acoustical Society of America, the American Institute of Ultrasound in Medicine, the Wallace H. Coulter foundation, the Bodossaki foundation, the Society of Photo-optical Instrumentation Engineers (SPIE) and the Radiological Society of North America (RSNA).

Focused ultrasound neuromodulation of visual pathways in humans

We carried out an investigation in 18 healthy volunteers in which 500 kHz ultrasound was focused to two visual brain areas: MT and FFA.  Target sites in participants were identified using MRI.  Computer modelling was used to determine the optimal placement of a single element transducer in order to insonify target regions on the right hemisphere and to ensure exposure parameters were limited. In the trials, the transducer was mounted to an arm an positioned using a neuronavigation system.  Subjects were instrumented with EEG electrodes and asked to carry out behavioral tasks: either detecting motion of dots or identifying faces.  The 500 kHz ultrasound was modulated with a 1 kHz square wave and participants could perceive audible sound during FUN which was confirmed by the presence of an auditory evoked potential in EEG recordings.  Ex vivo skull experiments suggested that ultrasound was absorbed by the skull resulting in a 1 kHz flexural wave that propagated to the ear canals.  We were able to mask the auditory confound by playing a 1 kHz tone through earphones while FUN was applied.  For the behavioural task preliminary analysis suggests that ultrasound neurostimulation resulted in improvement  in performance at the threshold for movement coherence when MT was targeted.  When FFA was targeted there was an improvement in hit-rate for facial recognition just below threshold and an increase in the amplitude of the N180 ERP.  In conclusion our results show that auditory masking can be employed to blind participants to an auditory confound and that ultrasound neurostimulation can modulate the response to visual stimuli at threshold in both MT and FFA.

Robin Cleveland, PhD

Cleveland

Robin Cleveland is a Professor of Engineering Science at the University of Oxford.  His research is conducted at the Institute of Biomedical Engineering and active areas include:  therapeutic use of ultrasound for ablation and drug delivery, ultrasound neuro-modulation, mechanisms of traumatic brain injury, and the use of shock waves to break kidney stones.  Professor Cleveland obtained the BSc and MSc degrees in Physics from the University of Auckland in New Zealand and the PhD degree in Mechanical Engineering from the University of Texas at Austin where his doctoral research was on sonic boom propagation in the atmosphere.  He was award the F.V. Hunt Fellowship of the Acoustical Society of America which he carried out at the University of Washington in Seattle studying shock wave lithotripsy.  He was a faculty member at Boston University for 14 years before moving to Oxford in 2011.  He is a Fellow of the Acoustical Society of America and a past Associate Editor of the Journal.  He was the Scientific Chair of the 2019 International Symposium on Therapeutic Ultrasound, and the Chair of the 2021 International Symposium on Nonlinear Acoustics.

Localized disruption of plasma-protein-binding of pharmacological agents using transcranial focused ultrasound: Road to another mode of neuromodulation

Transcranial focused ultrasound (tFUS)-based strategies for non-invasive and localized neuromodulation are rapidly expanding; however, the effects of plasma protein binding (PPB), which plays an important role in drug pharmacokinetics, particularly for central nervous system drugs, have long been overlooked. We demonstrate the non-invasive and localized unbinding of PPB from phenytoin, an anti-epileptic drugs with high affinity to albumin, using FUS delivered at a fundamental frequency of 250 kHz in a pulsed manner (55 ms tone burst duration, 4 Hz pulse repetition frequency), at 5 W/cm2 spatial peak pulse average intensity (Isppa). No microbubble-based ultrasound contrast agent was used. Equilibrium dialysis was performed on the sonicated buffered-saline containing therapeutic concentration of phenytoin and bovine serum albumin, and yielded a 27.7% elevation in the level of unbound phenytoin compared to an unsonicated control. Sonication of a brain hemisphere in rats (n = 10) that received intraperitoneal phenytoin, though immunohistochemistry (IHC) assessment, showed elevated regional phenytoin uptake compared to the unsonicated hemisphere, without actively disrupting the BBB. Temperature change was not seen. These findings demonstrate the use of FUS as a novel technique for spatially-selective unbinding of PPB, which may alter a wide range of drug–plasma protein interactions. The study suggests the utiliy of trancranial FUS in elevating local concentration of a free, unbound pharmaceutical agent and subseuqent neuromodulatory effects by the agent.

Seung-Schik Yoo, Ph.D., MBA

https://projects.iq.harvard.edu/ntel

Yoo

Seung-Schik is an associate professor of Radiology at Harvard Medical School, and is a director of Neuromodulation and Tissue Engineering Laboratory (NTEL), Brigham and Women's Hospital. He also serves as a faculty member of Mind Brain Behavior at Harvard University.  He received his Ph.D. in Radiological Science from the Harvard-MIT Division of Health Sciences and Technology (HST) after graduating from Johns Hopkins University majoring in Biomedical Engineering. 
He has done early pioneering works in developing real-time functional magnetic resonance imaging that are used to interpret the human mind, and applied the technology to interface the brain function with machines and computers. The main focus of his current research is in exploring a new mode of non-invasive brain stimulation modality which utilizes the focused ultrasound to control regional neural functions, including the activity of the brain. He is primarily interested in advancing the technique for various neurotherapeutics, but also likes to seek out new ways to link thoughts/brain processes between individuals.  He is a fellow and a recipient of Distinguished Investigator Award from the Academy for Radiology and Biomedical Imaging Research and the Mind Brain Behavior Interfaculty Initiative (MBB) faculty award from Harvard College. He recently nominated for Jolesz Memorial Award from Focused Ultrasound Surgery Foundation for his contributions to the field. Seung-Schik's research interest also includes development and application of a three-dimensional bioprinter that can produce artificial biological tissues and organoids for potential applications in neural computers and medical applications. He has been conducting extensive collaborations in 3D bioprinting in various disciplines, including stem cell research.

Focused Ultrasound induced BBB permeability enhancement and its potential for neuromodulation

When combined with imaging guidance focused ultrasound (FUS) provides means for localized delivery of mechanical energy deep into tissues. This focal energy deposition can modify tissue function via direct thermal or mechanical interactions with the tissue.  The impact of an ultrasound exposure can be  potentiated by intravascular microbubbles (MB). FUS in combination with MBs has been extensively explored for the enhancement of the permeability of the blood-brain barrier (BBB) and it has been shown to be  an effective method for local delivery of molecular agents, particles and even cells into targeted locations of the brain. The first clinical trials will be reviewed and demonstrate feasibility and safety in a clinical setting. The potential of this method for neuromodulation will be discussed.

Kullervo Hynynen, PhD

Hynynen

Kullervo Hynynen, Ph.D. is Professor in the Department of Medical Biophysics at the University of Toronto and the Director of Physical Sciences Platform at the Sunnybrook Research Institute, Toronto, Canada. He received his Ph.D. from the University of Aberdeen, UK and then had a faculty position at the University of Arizona where he developed several ultrasound devices from ideas to clinical trials and was the first to integrate focused ultrasound(FUS) transducers with an MRI scanner. He joined the faculty at the Harvard University, and BWH in 1993. There he founded the FUS Laboratory and developed MRI guided FUS surgery methods for clinical testing. These included breast tumor, uterine fibroid, and brain ablation devices. He transferred the technology to InSightec that is now commercializing them. He and his team discovered how to safely enhance the permeability of the blood-brain barrier (BBB) using FUS and established the safety and efficacy of the method. In 2006 he moved to Toronto where he has continued his research on brain treatments by using FUS for ablation and to enhance the permeability of the BBB. He has also continued to develop fully electronically steered phased transmit and receive arrays, developed super-resolution methods and continued to investigate the bio-effects of ultrasound alone and when combined with other therapy methods. He has had a continued interest in exploring the use of ultrasound for neuromodulation and its potential clinical translation.

Tools from biological physics to investigate the mechanisms underlying ultrasound neuromodulation across the scales

For historical reasons inherited from the field of biomedical ultrasound the most common working hypotheses to explain neuromodulation produced by low intensity focused ultrasound (FUS) are thermal rise and cavitation. However recent evidence has not confirmed these hypotheses and points towards other mechanisms such as changes in the action potential produced by the electrophysiological-mechanical coupling in the neuronal membrane to explain neuromodulation by FUS (Jerusalem et al. Acta Biomaterialia 2019). Recent advances in atomic force microscopy (AFM) has made it possible to investigate the effect of acoustic signals on membranes and living cells with nanometre resolution (Al-Rekabi, Contera, PNAS 2018) in a large range of time scales (from Hz to MHz) . In my talk I will introduce the techniques we are developing to study the effect of ultrasound on membranes and cells mechanical properties, I will also discuss how ultrasound can potentially modulate the synchronisation of neurons by altering the mechanical properties of brain tissues across the scales.

Contera

Biomolecular Engineering for Focused Ultrasound Control of Cellular Function

The study of biological function in intact organisms and the development of targeted cellular therapeutics necessitate methods to image and control cellular functionin vivo. Technologies such as optogenetics serve this purpose in small, translucent specimens, but are limited by the poor penetration of light into deeper tissues. In contrast, non-invasive techniques such as ultrasound – while based on energy forms that penetrate tissue effectively – are not as effectively coupled to cellular function. Our work attempts to bridge this gap by engineering biomolecules with the appropriate physical properties to interact with sound waves, and to enhance the transport of engineered biomolecules into tissues such as the brain. In this talk, I will focus on our work to understand the biophysical, molecular, and circuit mechanisms by which ultrasound can directly modulate neural activity, and methods of combining ultrasound with viral vectors and engineered receptors to enable convenient, scalable and cell-type specific control of neural circuits. In addition, I will describe two classes of biomolecular acoustic actuators that may in the future be applied to the brain. One is based on temperature-dependent transcriptional repressors, which provide switch-like control of gene expression in response to small changes in temperature. Another is based on genetically encodable air-filled protein nanostructures known as gas vesicles, which can be converted to free bubbles using low frequency ultrasound, enabling them to serve as molecularly targeted or genetically encoded seeds for inertial cavitation. 

Mikhail G. Shapiro, PhD

shapiro

Mikhail Shapiro is a Professor of Chemical Engineering and an Investigator of the Heritage Medical Research Institute at Caltech. The Shapiro laboratory develops biomolecular technologies allowing cells to be imaged and controlled inside the body using sound waves and magnetic fields to enable the study of biological function in vivo and the development of cell-based diagnostic and therapeutic agents. Mikhail received his PhD in Biological Engineering from MIT and his BSc in Neuroscience from Brown, and conducted post-doctoral research at the University of Chicago and the University of California, Berkeley, where he was a Miller Fellow. Mikhail’s awards include the Packard Fellowship, the Pew Scholarship, the Camille Dreyfus Teacher-Scholar Award and the Roger Tsien Award for Excellence in Chemical Biology. More information about the Shapiro Lab can be found online at shapirolab.caltech.edu

Single element low intensity transcranial focused ultrasound for human neuromodulation applications

Low intensity transcranial focused ultrasound (LIFU) is a promising non-surgical low-energy technique for transient neuromodulation with high spatial resolution and adjustable focus suitable for targeting cortical and sub-cortical human brain regions. Here, we will discuss current state of the art as well as progress and challenges for developing LIFU for human clinical applications. 

Wynn Legon, PhD

Wynn Legon

Assistant Professor, Department of Neurosurgery University of Virginia

Dr. Legon studies the use of ultrasound for cortical and sub-cortical neuromodulation in humans using EEG, fMRI, computer modelling and empirical testing in an effort to advance ultrasound for potential neurological diagnostic and therapeutic applications in health and disease.

Antoine Jérusalem, PhD

Jerusalem

Research by Professor Antoine Jerusalem and his team focusses on electrophysiological-mechanical coupled pulses in neural membranes. This endeavour is set to benefit the medical community in the diagnosis, prognosis, and treatment of Traumatic Brain Injury and Spinal Cord Injury, both major, global public health issues, while providing new avenues for non-invasive electrophysiological control, such as pain management.

HIFU ablation in the brain: diseases and targets

Suzanne LeBlang, MD

FUS Foundation

Director of Clinical Relationships
LeBlang

With her prior clinical experience as a neuroradiologist and having performed hundreds of focused ultrasound procedures, Suzanne LeBlang, MD, now represents the Foundation by interacting with various manufacturers and clinicians to foster collaborations. She interfaces with the medical community including clinicians and societies at various meetings in order to update the Foundation staff. In coordination with the communications team, she helps increase awareness through oral presentations and articles. She also assists the Chairman and the development team with building relationships with individuals and other foundations. She has published papers and delivered numerous scientific talks in the field of focused ultrasound. Suzanne received her B.A. in Biology and M.D. degree from the University of Miami 6 year Honors Program in Medical Education. She serves on the faculty at the University of Miami Medical School where she is the Radiology Clinical Coordinator for 3rd year M.D./M.P.H. students, and she teaches at the Florida Atlantic University Schmidt College of Medicine. She has been visiting faculty at several institutions including Harvard University and Ohio State University.

Computational methods for dosimetry

Computational methods for dosimetry allow estimating and optimizing the spatial distribution and strength of the ultrasound waves transmitted to the brain. These calculations are based on detailed models of the head anatomy that are derived from medical imaging data. In this talk, I will review the state-of-the-art in computational dosimetry for focused ultrasound neuromodulation, and discuss the remaining challenges.

Bradley E. Treeby, PhD

Treeby

Bradley E. Treeby is an Associate Professor in the Department of Medical Physics and Biomedical Engineering, University College London, and co-author of the open-source k-Wave acoustics Toolbox. He received the 2017 R. Bruce Lindsay Award from the Acoustical Society of America for  “contributions to the modeling of biomedical ultrasound fields.”

Non-invasive long-lasting modulation of deep brain circuits with ultrasound

To understand brain circuits we need to more than measurement; we need to modulate neural activity as well. This is even more critical in a clinical context. Current interference techniques are either highly invasive, or restricted to the surface of the brain. Focused transcranial ultrasound has the potential to overcome these limitations. I will discuss how we can use low-intensity ultrasound to safely stimulate deep brain structures, such as the amygdala, with high precision. To date, effects were short-lived, limiting its relevance to the clinic. In pioneering non-human primate work, we showed how a novel repetitive protocol induces hour-long plastic changes. Whole-brain fMRI allowed us to track how ultrasound impacted both local and remote circuits. Behavioural measurements revealed the specific consequences of a focal neural perturbation on cognitive computations. I will discuss work on the causal roles of the anterior cingulate cortex, amygdala, basal forebrain, and ventromedial prefrontal cortex in decision-making and learning.

Lennart Verhagen, PhD

Verhagen

To understand the brain and mind, and especially to advance new options in the clinic, it is as important to stimulate neural circuits as it is to measure from them. I focus my research on non-invasive imaging and modulation techniques in humans and other primates. I have a particular interest in the opportunities provided for non-invasive deep brain stimulation using low-intensity transcranial ultrasound stimulation.

Transcranial MR-guided Focused Ultrasound Neuromodulation of The Thalamic Visual Pathway

In a large animal model and using MR-ARFI targeting, we studied the effect of transcranial focused ultrasound sonication of the lateral geniculate nucleus on visual evoked potentials. Our study included a histological evaluation of all sonicated locations with neuromodulatory pulses and with MR-ARFI pulses. We found that focused ultrasound reversibly suppressed the VEPs peak-to-peak amplitude compared to controls, and returned to baseline gradually over 1 hour, with the suppression proportional to the focal intensity. Our histological study showed no differences between sonication locations and control.

The soliton theory for nerve excitation and the time-scales of excitation

The soliton theory provides an alternative explanation for the nervous impulse based on cooperative melting transitions in the biomembrane.  It relies on reversible electromechanical processes and the thermodynamics of membranes. During the nervous impulse, the membrane is shifted through its transition, with associated changes in heat capacity, compressibility and inherent time-scales. The latent heat of the transition explains the sign and the magnitude of the experimentally observed reversible heat production of the action potential and the observed changes in nerve dimension (shortening and increase in membrane thickness). The dimensional changes give rise to the possibility to excite the nerve mechanically or thermally.

In the transition, one finds fluctuations in the membrane permeability corresponding to spontaneous pore formation, which in a patch clamp experiment are indistinguishable from the quantized current events usually attributed to protein channels.  They show most features of protein channels including temperature- and mechano-sensitivity, and voltage-gating. Their characteristic open time scales can be understood in the context of the fluctuation theorems applied to a membrane.

Membrane fluctuations therefore provide an estimate for the most suitable time-scale of membrane excitation. After a perturbation, relaxation processes in artificial membranes may display relaxation time scales up to several seconds. In biomembranes close to transitions, the expected relaxation time scales are expected to be in the millisecond regime. This is also the time scale of the open-lifetimes of membrane pores - and as it happens, the typical lifetime of protein channels. Therefore, we argue that this is also the time-scale of the most effective nerve membrane excitation.

Manipulation of subcortical and deep cortical activity in the primate brain using transcranial focused ultrasound and its effects on learning and decision-making

Focused Transcranial Ultrasound Stimulation enables us to non-invasively and transiently modulate activity in subcortical and deep cortical brain structures, without the need of any surgical procedure. I am particularly interested in using low-intensity ultrasound stimulation to investigate the neural and behavioural effects resulting from a transient interference of neural communication between different brain regions within a circuitry. The capacity of transcranial focused ultrasound stimulation to alter activity in regions located deep below cortex will allow us to better understand the contribution of these structures to normal and pathological cognition.

Davide Folloni

Davide Folloni

Davide Folloni is a PhD student in Neuroscience interested in understanding the functional dynamics of the neural circuits supporting learning and decision making. Its research uses a multi-modal approach to describe the anatomy, organization and neural activity of different brain networks. Specifically, he uses transcranial focused ultrasound stimulation in combination with functional Magnetic Resonance Imaging to manipulate the activity of subcortical and cortical brain structures and causally infer their role in normal and abnormal cognitive computations underlying decision-making.

Ultrasound neuromodulation: combining with fMRI, localizing the focus, and understanding mechanisms

Ultrasound has the ability to focus energy to a small point beyond the skull and is being widely explored by researchers as a tool for non-invasive neuromodulation. When combined with magnetic resonance imaging (MRI), focused ultrasound (FUS) can be precisely guided while the effects of FUS can be visualized at the network level using fMRI. In this talk, I will discuss our ongoing work in developing systems to apply image-guided FUS neuromodulation in the MRI environment while imaging functional activity. Specifically, I will cover the development of optical tracking as a method to guide FUS neuromodulation, the creation of transducer arrays for steerable FUS neuromodulation, and the development of MR acoustic radiation force imaging methods to visualize the acoustic focus. We have used these methods to modulate the somatosensory network in non-human primates, demonstrating that MRI-guided FUS is capable of exciting precise targets in somatosensory areas 3a/3b, causing downstream activations in off-target brain regions within the circuit which we simultaneously detected with fMRI. Our observations are consistent with others’ work in the field of FUS neuromodulation; however, questions remain about mechanisms underlying FUS neuromodulation and potential confounds. The talk will conclude by reporting on recent work at the cellular level where we are measuring calcium signaling in mouse brain slices with optical markers during FUS neuromodulation.

Charles F. Caskey, Ph.D.

Caskey

Charles F. Caskey, Ph.D.

Assistant Professor, Vanderbilt University Institute of Imaging Science

Vanderbilt University Medical Center

Department of Radiology & Radiological Sciences

 

Dr. Caskey has worked in the field of ultrasound since 2004. He received his doctoral degree for studies about the bioeffects of ultrasound during microbubble-enhanced drug delivery under Dr. Katherine Ferrara at the University of California at Davis. As a postdoctoral scholar and research scientist, he worked on applications with ultrasound thermometry, MR-guided focused ultrasound, and ultrasound hyperthermia. Dr. Caskey is currently an assistant professor at Vanderbilt University Medical Center where his laboratory focuses on therapeutic and diagnostic uses of ultrasound and multimodal image-guided therapy.

Experimental validation of modelled acoustic pressure fields for neuromodulation in the deep brain

Accurate computational models of ultrasound propagation through the skull are essential for optimising, planning, and delivering ultrasonic neuromodulation in the brain. To evaluate their accuracy, models of transcranial ultrasound propagation are validated against measurements of ultrasound fields after propagation through human skulls. I will discuss our approach to performing these validation studies, the sources of uncertainty, and the challenges involved. I will also give an overview of the datasets used for validation. These include micro CT and clinical CT scans of skulls, and ultrasonic source characterisations, and will be made publicly available via the UCL open access data repository.

Elly Martin, PhD

Martin

Elly Martin is a Research Associate in the Biomedical Ultrasound Group in the Department of Medical Physics and Biomedical Engineering at UCL working in ultrasound metrology. Her current research interests include model validation, and the design and characterization of multielement arrays for therapeutic ultrasound.

organizers

sallet

Jerome investigates the neurobiological basis of adaptive behaviors in human and non-human primates. He completed a PhD in cognitive neuroscience from Lyon 1, before joining the University of Oxford. He is currently a PI at the Department of Experimental Psychology in Oxford.

stagg

Charlotte J Stagg MRCP DPhil

Dr Charlotte (Charlie) Stagg is Professor of Human Neurophysiology and Head of the Physiological Neuroimaging Group at the Wellcome Centre for Integrative Neuroimaging (WIN), University of Oxford, UK. She has held a Sir Henry Dale Fellowship, funded by the Wellcome Trust and the Royal Society, since 2014.

Her inter-disciplinary group uses multi-modal neuroimaging and non-invasive brain stimulation approaches to understand the physiological processes underlying motor plasticity, both in the context of learning new motor skills and regaining function after a stroke. Her work has two overarching themes: to understand the mechanisms underpinning motor learning, and to develop non-invasive brain stimulation as a potential therapeutic intervention for rehabilitation.

https://www.ndcn.ox.ac.uk/research/physiological-neuroimaging-group

twitter: @cjstagg

Antoine Jérusalem, PhD

Jerusalem

Research by Professor Antoine Jerusalem and his team focusses on electrophysiological-mechanical coupled pulses in neural membranes. This endeavour is set to benefit the medical community in the diagnosis, prognosis, and treatment of Traumatic Brain Injury and Spinal Cord Injury, both major, global public health issues, while providing new avenues for non-invasive electrophysiological control, such as pain management.

Lennart Verhagen, PhD

Verhagen

To understand the brain and mind, and especially to advance new options in the clinic, it is as important to stimulate neural circuits as it is to measure from them. I focus my research on non-invasive imaging and modulation techniques in humans and other primates. I have a particular interest in the opportunities provided for non-invasive deep brain stimulation using low-intensity transcranial ultrasound stimulation.

fun.web.ox.ac.uk//
16/10/2019 04:26:43
List of site pages