Alan Urban (KU Leuven): Functional ultrasound imaging (fUSi) of intact brain circuit dynamics at large scale
Functional ultrasound imaging (fUSi) is an innovative modality based on plane-wave Doppler ultrasound for detection of small hemodynamic changes in brain vessels triggered by neuronal activity. The benefits of fUSi include a good spatial (< 100um3 voxel size), a good temporal resolution (<100ms), a high sensitivity, a large field of view (several cm2), an extended compatibility with electrophysiological recordings (tetrodes, silicon probes,…) and with the optogenetic interrogation of neural circuits. Our group has recently demonstrated that fUSi can reliably map sensory-evoked responses across several synapses during tasks without the need for temporal averaging which offers a new way to decipher the complex links between brain activity and behavior. fUSi allows precise study cerebral blood flow regulation and neurovascular dysfunction in pathologies such as stroke, Alzheimer disease, traumatic brain injury or glioblastoma. Additionally, it provides reliable data for middle throughput screening during pharmacological studies (i.e. target validation, measure of off-target effects…). On the bedside, fUSi has unique assets for diagnose and non-invasive monitoring of brain activity in neonates and also for precise identification of eloquent brain regions during resection of epileptic foci and/or brain tumor. A new generation of fully digital fUSi scanner with 3D real-time imaging capabilities is currently in development in our team at the NERF.
Mark Woolrich (University of Oxford): Brain network dynamics
Large-scale functional brain networks are most commonly estimated by averaging brain activity over time. However, the brain processes information through the dynamics of distributed neuronal activity. For example, when learning a sequence of sensory events that lead to a reward, cell assemblies in memory, reward and sensory networks dynamically interact in a coordinated manner. In this talk I will present novel approaches that aim to understand how large-scale networks dynamically interact over time in order to coordinate these underlying cell assemblies. Specifically, we use Hidden Markov Models (HMMs) to describe network dynamics across a range of modalities, including invasive local field potential (LFP) recordings, magnetoencephalography (MEG) [Quinn2018, Vidaurre2018] and fMRI [Vidaurre2017]. I will describe how this can be used to estimate the rate of occurrence of networks, the switching between networks, and spatial patterns of brain network dynamics, all over a range of time-scales relevant to behaviour; i.e., from milliseconds (in electrophysiology) to seconds/minutes (in electrophysiology and fMRI).
Simon Schultz (Imperial College London): Multiphoton imaging of hippocampal place cell network activity in mouse models of neurodegenerative disease
Mouse models of Alzheimer’s Disease (AD) incorporating amyloid beta (Aβ ) pathology have been used to study the relationship between extracellular Aβ and cortical circuit function, as well as behavioural performance on spatial memory tasks. In vivo multiphoton microscopy has much promise as a tool for revealing the relationship between specific changes in circuit properties, and memory performance. In this talk, I will describe a platform that we have developed for characterising functional changes in memory circuitry in mouse models of neurodegenerative disorders. We inject hippocampal subfield CA1 with AAV-hSyn1-mRuby-GCaMP6s, which labels neurons with both a green genetically encoded calcium indicator, and an activity-independent red fluorescent marker. This has the advantage of allowing us to select cells for processing in a manner unbiased by their neural activity. A chronic imaging window is implanted, and network activity imaged using a resonant scanning 2P microscope. The mice are head-fixed, and perform a spatial memory task in a flat-real world environment with visuotactile cues, consisting of a carbon-fibre maze floating on an airbed under the microscope. We find that a substantial proportion of CA1 cells show place fields in a circular linear track task in this platform; we observe remapping in alternate familiar environments (testing memory recall), and can also observe the formation of new maps (testing memory encoding) in real time, with quantitative measurement of each cell’s contribution to performance using information theory. For each imaged cell, the local amyloid load can be computed (labelling plaques by i.p. injection of Methoxy-X04), and related to its contribution to memory encoding and recall performance. We propose that the platform we describe here may be a powerful and general tool for characterising the contributions of circuit properties to dementia, as well as the effect of therapeutic strategies.
Zoltan Takats (Imperial College London):
Professor Zoltan Takats and his research group develop innovative mass spectrometry based diagnostic techniques that can be applied to a wide range of areas. The multi-disciplinary research group draws expertise from a range of areas and comprises clinical research fellows, post-doctoral researchers, research nurses, biomedical scientists and technicians. Desorption Electrospray Ionization (DESI) mass spectrometry imaging (MSI), an ambient ionization technique developed in 2004, allows analysis and imaging of samples under ambient conditions with minimal sample pre-treatment. DESI-MSI has been extensively used by our group for a range of purposes. The biochemical information uncovered by DESI-MSI provides a potentially faster diagnostic tool. Our DESI-MSI research provides novel biomarkers and therapeutic targets that may be used for detection and treatment.
Matthew Brookes (University of Nottingham): Quantum sensing the brain: next generation neuroimaging
In recent years optically-pumped magnetometers (OPMs) have been emerging as highly sensitive magnetic field sensors, and OPMs are now a viable alternative to superconducting quantum interference devices (SQUIDs) for many biomagnetic measurements, including those from the brain. In this talk, I will outline the latest developments in the use of OPMs for magnetoencephalography (MEG) measurement. I will begin by explaining the basic premise behind scalp mounted sensor arrays, showing the results of simulation studies which demonstrate the potentially vast improvements in sensitivity and spatial resolution that are afforded by a move from superconducting to body temperature magnetic field sensors. Following this, I will explain the basic mode of operation of the OPM sensor itself, and highlight some of our initial measurements that were made with the first available commercial OPMs. We will touch on fundamental technical issues such as cross-talk and gain errors within the sensor array itself, magnetic shielding, and the use of novel electromagnetic coils to null static background fields, thus enabling the capture of high fidelity MEG measurements even whilst a subject is free to move. I will describe the latest measurements that have been made using OPM arrays; this will include sensorimotor metrics of beta band oscillations, demonstrations of retinotopy in the visual cortex, and also examples of the use of a bilateral (36 channel) OPM array to do language lateralization. Finally, I will highlight future perspectives for OPM MEG development and application, particularly touching in the potential use of OPMs for dementia.
Paul Beard (University College London): Photoacoustic imaging of the brain
Photoacoustic imaging is a new biomedical imaging modality based on the use of laser-generated ultrasound. It is a hybrid technique that combines the high contrast and spectroscopic-based specificity of optical imaging with the high spatial resolution available to ultrasound. As a consequence, it overcomes the limited penetration depth/spatial resolution of purely optical imaging techniques such as multiphoton microscopy or diffuse optical tomography due to the overwhelming optical scattering exhibited by tissue. At the same time, it retains their high contrast and spectral specificity enabling visualisation of anatomical features indistinguishable with other modalities such as ultrasound imaging. The technique has several specific features that make it a potentially powerful neuroimaging tool. First, it can provide 3D images of vascular anatomy with high spatial resolution and contrast, the latter being a consequence of the strong absorption of haemoglobin at visible and near-infrared wavelengths. Second, it can reveal the distribution of blood oxygen saturation over the vasculature by obtaining images at multiple wavelengths and exploiting the spectral differences between oxy and deoxyhaemoglobin. Third, by extracting the Doppler shift from photoacoustic waves generated in red blood cells, measurements of blood flow can be acquired. As well as exploiting endogenous contrast provided by haemoglobin, there is also the potential, through the use of targeted contrast agents or genetic reporters to provide information at a cellular/molecular level. These attributes lend photoacoustic imaging to the study of small animal cerebral haemodynamics, oxygenation and cellular function. Potential applications include studying neurovascular coupling, functional stimulation and the characterisation of mouse models of brain injury and disease including stroke, epilepsy and Alzheimer’s.
George Malliaras (University of Cambridge): New materials and devices for interfacing with the brain
Current technologies for interfacing with the brain are limited by the materials that are brought in contact with the tissue and transduce signals across the biotic/abiotic interface. Recent advances in organic electronics have made available materials with a unique combination of attractive properties, including mechanical flexibility, mixed ionic/electronic conduction, enhanced biocompatibility, and capability for drug delivery. I will present examples of novel devices for recording and stimulation of neurons and show that organic electronic materials offer tremendous opportunities to study the brain and treat its pathologies.
