Functional Ultrasound Neuroimaging in Awake & Behaving Non-Human Primates
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To learn more and watch the webinar, go to: https://insidescientific.com/webinar/functional-ultrasound-neuroimaging-in-awake-behaving-non-human-primates/ While there are many neuroimaging modalities to study the brain, each comes with its own set of benefits and limitations. MRI and EEG can record from the whole brain, but it comes at the price of limited spatiotemporal resolution and low sensitivity. Recently, functional ultrasound (fUS) imaging has made a name for itself, with its ability to image the full depth of the brain and provide a quantitative view of brain activation and connectivity. In this webinar, Dr. Pierre Pouget discusses the use of fUS imaging to assess local changes in cerebral blood flow in awake, behaving non-human primates. He provides an overview of fUS technology and highlight recent and ongoing research showing how unexpected functions can be tracked in the fronto-medial cortex. Dr. Serge Picaud discusses the application fUS imaging to study the neural circuits underlying vision in rats and nonhuman primates. He presents recent research using fUS in rats to study activation of the visual system, and in NHPs to map brain activity and to study ocular dominance columns in the visual cortex. Key topics will include: Pierre Pouget - Using fUS to assess brain activity in non-human primates in a single trial, without averaging - Possibilities when coupling fUS with electrophysiology and pharmacology - How fUS imaging can be used to track short and long-term variations in brain activation Serge Picaud - Studying activation of neuronal circuits with either prosthetics or optogenetic activation - Procedure to generate retinotopic maps in behaving non-human primates - Demonstrating the lateral and spatial resolution of fUS by imaging ocular dominance columns
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Functional Ultrasound Neuroimaging in Awake & Behaving Non-Human Primates
- 1. Functional Ultrasound Neuroimaging in Awake and Behaving Non-Human Primates Serge Picaud, PhD Director INSERM Vision Institute France Pierre Pouget, PhD CNRS Principal Investigator Brain and Spine Institute
- 2. Functional Ultrasound Neuroimaging in Awake and Behaving Non-Human Primates Dr. Pierre Pouget and Dr. Serge Picaud provide an overview of functional ultrasound imaging and how it can be used to study the brain in behaving non-human primates.
- 3. Using Ultrasounds to Study the Brain of Non-Human Primates Pierre Pouget, PhD CNRS Principal Investigator Brain and Spine Institute Copyright 2021 P. Pouget, InsideScientific and Iconeus. All rights reserved.
- 4. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Ultrasound Imaging
- 5. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Electrical Pulse Electrical Signal Image Transducer Ultrasound Imaging
- 6. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com CONVENTIONAL DOPPLER ULTRAFAST DOPPLER E. Macé, G. Montaldo, I. Cohen, M. Baulac, M. Fink, M. Tanter. Functional Ultrasonic Imaging of Brain Activity, Nature Methods, July 2011 Brain Imaging with Doppler Imaging
- 7. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com 2 mm Study of Brain Activity: Functional Ultrasound Imaging Allows the determination of functional hyperemia Sensitive to Cerebral Blood Volume (CBV) ΔVSC (%)
- 8. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com ACC SEF 10 mm 14 mm Dizeux et al. (2019). Nat. Com. Cerebral Blood Flow Recording in Macaque Monkey
- 9. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Brain activity in awake behaving monkeys
- 10. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com No rule Rule 14 mm 10 mm SEF control region Brain activity in awake behaving monkeys Dizeux et al. (2019). Nat. Com.
- 11. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com No rule Rule Time (s) 0 300 200 100 CBV in % of baseline 120 0 60 Frequency (Hz) 0.0 7.0 3.5 cardiac pulsatility brain activity 0.35 Hz Normalized amplitude (a.u.) 0 1 4s 40s t0 0.4s 0.04 s fUS signal, sampling frequency: 500Hz brain activity cardiac pulsatility harmonic 60 80 100 40 0 20 40 60 80 CBV in % of baseline Time (s) trial start No rule Rule 250ms sliding window with 10ms steps plateau Functional ultrasound imaging enable single trial detection of SEF activation No rule Rule 14 mm 10 mm SEF control region Dizeux et al. (2019). Nat. Com.
- 12. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com CBV > 1𝝈 CBV > 2𝝈 CBV > 3𝝈 Large ROI 1.4 ± 0.6 s 1.8 ± 0.5 s 2.0 ± 0.5 s 1-pixel ROI 1.5 ± 0.5 s 2.0 ± 0.5 s 2.3 ± 0.5 s 𝝈: standard deviation of baseline Average time obtained over 85 acquisitions Large ROI 1pixel ROI Control region SEF p-value: 1.7e-29 p-value: 1.6e-33 1-pixel ROI Large ROI trial start t0 trial start t0 + 2.5s trial start t0 trial start t0 + 2.5s trial start t0 trial start t0 + 2.5s trial start t0 trial start t0 + 2.5s Each pair of point (red-green) represent an acquisition with a total of 85 acquisitions CBV in %of baseline 150 100 50 0 -50 CBV in %of baseline 100 50 0 -50 trial start: t0 t0 + 1.5s t0 + 2.5s 1mm A B C 0 100 40 20 60 80 CBV in % of baseline 1𝜎 2𝜎 3𝜎 No rule Rule t0 0 20 40 70 60 80 50 62 63 64 65 Time (s) CBV in % of baseline A B C trial-start SEF (large ROI) Time (s) (highest variation) Functional ultrasound imaging enable single trial detection of SEF activation Dizeux et al. (2019). Nat. Com.
- 13. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com http://www.cns.nyu.edu/~david/courses/perception/lecturenotes/brain/brain.html Single unit recording and Ice Fishing...
- 14. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com ACC SEF 10 mm 14 mm Claron et al. (in preparation) Can functional ultrasound imaging permit to localize microelectode?
- 15. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Claron et al. (in preparation)
- 16. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Claron et al. (in preparation) Functional ultrasound imaging permits to localize microelectode
- 17. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Macroscopic recording (fUS) (~ 2 mm²) Mesoscopic recording (LFP) (Ø 600 µm) Microscopic recording (SUA/MUA) (Ø 100 µm) Claron et al. (in preparation)
- 18. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Functional ultrasound imaging and Single Unit Activity Ultrafast Ultrasound Imaging Single Unit Activity Local Field Potential Ultrafast Ultrasound Imaging Single Unit Activity Local Field Potential
- 19. Confidential PIERRE POUGET, ICM, CNRS FRANCE pougetp@gmail.com Millisecond Second Minute Log time Hour Day Synapse Dendrite Neuron Layer Column Map Brain Log size Patch clamp Single unit Multi unit recording Optical dyes EEG & MEG TMS fMRI PET Lesion Micro lesion Light microscopy Ultrafast Neuro-functional Ultrasound Imaging Fundamentals of Cognitive Neuroscience. A Beginner's Guide. 2013, Pages 109-140 Methods for observing the living brain
- 20. Functional Ultrasound Neuroimaging: A tool for assessing visual restoration strategies Serge Picaud, PhD Director INSERM Vision Institute Copyright 2021 S. Picaud, InsideScientific and Iconeus. All rights reserved.
- 21. Functional Ultrasound Neuroimaging: a tool for assessing visual restoration strategies Serge Picaud, Institut de la Vision, Paris, France Conflicts of interest: Pixium Vision, Gensight Biologics, PropheSee, Iconeus (Pieter Bruegel, 1568)
- 22. Confidential Blind Vision impaired AMD Glaucoma Diabetes Vision loss is increasing with aging of the population
- 23. Confidential Macular degeneration Inherited dystrophies: RP Glaucoma Diabetes Diseases leading to blindness
- 24. Confidential Sub-retinal Macular degeneration Inherited dystrophies: RP Glaucoma Diabetes Cortical activation Concept of visual restoration: Stimulation of residual neurones in the visual system
- 25. Confidential Visual stimuli in anesthetized rats (Gesnik, Blaize et al., NeuroImage 2017)
- 26. Confidential Visual activation of the visual system (Gesnik, Blaize et al., NeuroImage 2017)
- 27. Confidential 3D reconstruction of the activated visual system (Gesnik, Blaize et al., NeuroImage 2017)
- 28. Confidential (Gesnik, Blaize et al., NeuroImage 2017) Retinotopy of the visual responses
- 29. Confidential fUS MRI Blaize et al., PNAS 2020 Functional ultrasound imaging in awake primates: Changes in cerebral blood volume
- 30. Confidential Blaize et al., PNAS 2020 Functional ultrasound imaging in awake primates: Retinotopic maps
- 31. Confidential Kennedy, PNAS, 1976 Blaize et al., PNAS 2020 Ultrasound functionnal imaging: Maps of ocular dominance and retinotopy LeVay, JN, 1985
- 32. Confidential (Palanker et al., Research Square 2021) Visual acuity: 20/460 - 20/565 (Palanker et al., Ophthalmology 2020) Fusion of prosthetic and natural vision Clinical trial: Age-related macular degeneration
- 33. Confidential Cortical responses by fUS InfraRed Visible
- 34. Confidential Ultrasound imaging IR 0.1mW/mm2 IR 0.3mW/mm2 IR 0.6mW/mm2 IR 1.2mW/mm2 IR 1.7mW/mm2 Visible
- 35. Confidential 1ms stimulation Retina Brain Clinical trials : - surgery - functionality Electrophysiology
- 37. Confidential (Sahel et al., Nature Medicine 2021) Optogenetic therapy: First in a human patient
- 38. Confidential Cortical expression of ChrimsonR (Provansal et al., 2021)
- 39. Confidential Optogenetic activation of cortical neurons expressing ChrimsonR (Provansal et al., 2021)
- 40. Confidential Corelation of electrophysiology and fUS inV1 (Provansal et al., 2021)
- 41. Confidential (Provansal et al., 2021) Corelation of electrophysiology and fUS in the LGN
- 42. Confidential - Functional recording of the visual system in rats - Temporal resolution of the activated areas - Retinotopic maps in the behaving non-human primates - Detection of the ocular dominance columns even in deep V1 (calcarine sulcus) - Functional detection of ocular dominance columns up to layer 5 - Functional response to prosthetic activation of the retina - Functional response to the optogenetic activation of the visual cortex - High correlation with electrophysiology - Easier detection of activity in a poorly activated LGN structure Conclusions
- 43. Mélissa Desrosiers Deniz Dalkara Antoine Chaffiol Jens Duebel Céline Nouvel-Jaillard Sarah Ayello-Scheer Stéphane Bertin Ryad Benosman Guillaume Chenegros Christoph Posch José Sahel MIRCEN Claire-Maelle Fovet Joanna Demilly Alexis Bemelmans Philippe Hantraye FMI Botond Roska Busskamp Volker Balya David MPI Biophysics Ernst Bamberg Gregory Gauvain Paul-Henri Prévot Fabrice Arcizet Matthieu Provansal Sara Cadoni Diep Nguyen Romain Caplette Guillaume Labernede Sami Dallouz Anna Vershueren Kevin Blaize Corentin Joffrois Leyna Boucherit Elisabeth Dubus Valérie Fradot Amel Bendali Mélanie Marie Emilie Arnault Henri Lorach Giulia Spampinato Olivier Marre INSERM CIC 503 Saddek Mohand-Said Michel Paques Isabelle Audo Pierre-Olivier Barale José Sahel Martin Deterre Guillaume Buc Daniel Palanker Georges Goetz Henri Lorach Stanford U Didier Pruneau Bernard Gilly ICM Pierre Pouget MIT Ed Boyden Fondation Rotschild Yannick LeMer Physique pour la Médecine Thomas Deffieux Mickael Tanter Bruno Osmanski Ludovic Lecointre
- 45. Thanks for participating! Before you go… 1. To learn more and watch the webinar, visit: https://insidescientific.com/webinar/functional-ultrasound- neuroimaging-in-awake-behaving-non-human-primates/ 2. To learn more about Iconeus functional ultrasound technology, visit: www.iconeus.com