The pulsing brain

26 - 27 June 2024 09:00 - 17:00 Leonardo Royal Brighton Waterfront Free
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MRI of the human brain

Theo Murphy meeting organised by Dr Andrea Lecchini-Visintini, Dr Emma Chung, Dr Jatinder Minhas and Professor Stephen Payne

Understanding the brain’s pulsing dynamics is an emerging research theme. Medical imaging and ultrasound researchers have developed methods to generate relevant data efficiently. Mathematical models require merging biomaterials and biofluids and transport frameworks. The main objectives of this meeting are to showcase existing data, to initiate the development of models, and to highlight key questions relevant to clinical translation.

Venue

This event is intended for researchers in relevant fields, and is a residential meeting taking place at the Leonardo Royal Brighton Waterfront hotel, King's Road, Brighton, BN1 2GS 

Attending this event

  • Free to attend and in-person only
  • Please request an invitation using the above link. When requesting an invitation, please briefly state your expertise and reasons for attending. Requests are reviewed by the meeting organisers on a rolling basis. You will receive a link to register if your request is successful
  • Catering options will be available to purchase upon registering. Participants are responsible for booking their own accommodation. Please do not book accommodation until you have been invited to attend the meeting by the meeting organisers

Enquires: please contact the Scientific Programmes team.

Organisers

  • Dr Andrea Lecchini-Visintini, University of Southampton, UK

    Dr Andrea Lecchini-Visintini, University of Southampton, UK

    Dr Andrea Lecchini-Visintini is a member of the Cyber-Physical Systems Research Group, School of Electronics and Computer Science, University of Southampton. His research has focused on data-based control-oriented modelling, with aerospace and biomedical application. In 2019-20, he held a RAEng Industrial Fellowship hosted at Rolls-Royce. He is currently an Associate Editor of the International Journal of Control.

  • Dr Jatinder S Minhas, University of Leicester, UK

    Dr Jatinder S Minhas, University of Leicester, UK

    Dr Minhas’s research endeavours to bridge the gap between technical studies in cerebrovascular physiology (particularly acute intracerebral haemorrhage), and delivery of clinical stroke care and research. He strongly believes this niche is vital for delivering technically excellent and innovative translational programmes of research with the potential to deliver significant improvements in stroke care, in reasonable time frames.

  • Professor Stephen Payne, National Taiwan University, Taiwan

    Stephen Payne is Professor and Yushan Fellow at National Taiwan University, Taipei, Taiwan. Prior to this he was Professor at the University of Oxford. He is the current Editor-in-Chief of the journal Medical Engineering and Physics. He has published around 140 papers in international journals, written 3 books, supervised over 30 PhD students to successful completion, and raised over £3.1M in research funding.

  • Dr Emma Chung, King's College London, UK

    Dr Emma Chung, King's College London, UK

    Emma is a Senior Lecturer with King’s College London and Research Lead for the University Hospitals of Leicester NHS Trust Medical Physics Department. Emma is a registered Clinical Scientist, and Fellow of the Institute of Physics with a special interest in Ultrasound Education and clinical translational ultrasound research. In 2020, Emma was highly commended by England's Chief Scientific Officer for her research using Doppler ultrasound for the detection of brain injury. Emma is a former Editor-in-Chief of the journal 'Ultrasound' and is a former Honorary Secretary of the British Medical Ultrasound Society (BMUS).

Schedule

Chair

Dr Samantha Holdsworth, Matai Medical Research Institute and University of Auckland, New Zealand

Dr Samantha Holdsworth, Mātai Medical Research Institute & University of Auckland, New Zealand

09:05-09:30 Probing the pulsing brain with MRI

Heartbeat-induced brain pulsations are thought to be important for maintaining brain homeostasis in the healthy brain. Changes in brain pulsations due to aging and/or vascular disease go hand in hand with disease processes that lead to dementia. Improving our understanding of the role of brain pulsations in health and disease requires methods that can non-invasively map these pulsations in humans. MRI has unique potential to measure multiple facets of brain pulsations. This lecture will start by sketching the cranial cavity and its contents, which set the stage for brain pulsations. Next, it will provide an overview of MRI methods that can probe the various aspects of pulsations in the intracranial cavity, including blood flow velocity pulsations, blood volume pulsations, brain tissue motion and deformation, and pulsations in the cerebrospinal fluid. By going over all these aspects, the lecture aims to provide an overview of the current understanding, together with the MRI methods that are available to further this understanding. Open questions and unmet needs regarding measuring brain and intracranial pulsations in its multiple facets will be highlighted.

Dr Jaco J M Zwanenburg, Translational Neuroimaging Group, Center for Image Sciences, UMC Utrecht, The Netherlands

Dr Jaco J M Zwanenburg, Translational Neuroimaging Group, Center for Image Sciences, UMC Utrecht, The Netherlands

09:45-10:15 Intrinsic brain motion as an imaging marker for diseases
10:30-11:00 Break
11:00-11:30 Dynamic diffusion-weighted imaging of pulsatile CSF dynamics in the paravascular space

Paravascular CSF dynamics have gained renewed research interest in neuroscience due to its recently discovered waste clearance function. Pulsation is considered a driving force behind its flow dynamics, yet challenges remain due to the limited non-invasive imaging techniques for studying the human brain.

This talk will introduce dynamic diffusion-weighted imaging, which has been specifically developed to detect pulsatile paravascular CSF dynamics in humans.

Assistant Professor Quiting Wen, Indiana University School of Medicine, USA

Assistant Professor Quiting Wen, Indiana University School of Medicine, USA

11:45-12:15 Unveiling tissue secret from natural brain vibrations

Elastography, sometimes referred as seismology of the human body, is an imaging modality now implemented on medical ultrasound systems, on MRI and recently in optical coherence tomography devices. It allows to measure shear wave speeds within soft tissues and gives a tomography reconstruction of the shear elasticity. The shear elasticity being the elasticity felt by fingers during palpation, elastography is thus a palpation tomography. In the first part of this presentation, a passive elastography method is described. Inspired by noise correlation seismology and time reversal, it allows to extract from natural shear waves produced in the human body by heart beatings, muscles activities, arterial pulsations, a shear wave speed estimation. Therefore, an elasticity palpation mapping with no shear wave source is conducted.

Professor Stefan Catheline, University of Lyon, France

Professor Stefan Catheline, University of Lyon, France

Chair

Professor Stephen Payne, National Taiwan University, Taiwan

13:30-14:00 Human brain tissue mechanics: experiments, modelling, and simulation

The brain is not only one of the most important but also the arguably most complex and compliant organ in the human body. While long underestimated, increasing evidence confirms that mechanics plays a critical role in modulating brain function and dysfunction. Computational models based on nonlinear continuum mechanics can help understand the basic processes in the brain, e.g., during development, injury, and disease, and facilitate early diagnosis and treatment of neurological disorders. 
This talk demonstrates how to develop computational models that capture both biological processes at the cellular scale and brain tissue behaviour under macroscopic loading and pathologies by closely integrating biomechanical experiments on human brain tissue, microstructural analyses, continuum mechanics modelling, and finite element simulations. The cell density is introduced as an additional field controlling the local tissue stiffness and brain growth during development. Like this, the models are capable of capturing the evolution of cell density and cortical folding in the developing brain as well as regional variations in tissue properties in the adult brain that are highly relevant for the stress and strain states during macroscopic loading to the brain.  In the future, those models can provide deeper insights into the behaviour of the human brain under physiological and pathological conditions, and more precise simulation to prevent and treat injury or disease. It will discuss its methodology, current findings in aging and disease cohorts, its limitations, and future potential.

Professor Silvia Budday, Institute of Continuum Mechanics and Biomechanics Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany

Professor Silvia Budday, Institute of Continuum Mechanics and Biomechanics Friedrich-Alexander-Universität Erlangen-Nürnberg, Germany

14:15-14:45 Computational models of the glymphatic system

The glymphatic theory propose a clearance system for the brain that is particularly active during sleep. The system is important as many neurodegenerative diseases are related to accumulation of metabolic waste. This talk will present an overview of computational models, current challenges and open questions. 

Professor Kent-Andre Mardal, University of Oslo, Norway

Professor Kent-Andre Mardal, University of Oslo, Norway

15:00-15:30 Break
15:30-16:00 Neuron multiphysics, a new paradigm for the building block of the brain

Neurons are traditionally considered solely through their electrophysiological function. They are however multiphysics systems whereby their physical properties – electrophysiological, mechanical, biochemical, etc. – are in fact working collaboratively and concurrently. In this presentation, we will demonstrate how this is indeed the case, and what the implications are for the general field of neuromodulation.

Professor Antoine Jerusalem, University of Oxford, UK

Professor Antoine Jerusalem, University of Oxford, UK

16:15-16:45 CSF dynamics in perivascular spaces

Flow of cerebrospinal fluid (CSF) in the in the perivascular spaces that surround cerebral blood vessels plays an important role in clearance of waste from the brain and is linked to diseases such as Alzheimer’s and small vessel disease. Recently, artificial intelligence velocimetry (AIV), which integrates sparse two-dimensional (2D) in vivo velocity measurements with physics-informed neural networks, has been used to infer high-resolution pressure, volumetric flow rates, and shear stresses of CSF in pial PVSs, providing a wealth of information about the dynamics of these flows. However, in the initial work, the PVS and vessel wall boundaries were assumed to be stationary, contrary to what has been observed in experiments. In fact, the motion of the vessel wall directly adjacent to the PVS is closely coupled to the CSF dynamics and is thought to drive the CSF flow. This talk will describe new results from an updated AIV model that incorporates moving blood vessel walls and residual-based attention to the physics-informed neural networks, quantifying the importance of including vessel wall motion in AIV inferences. The types and extent of vessel wall motion and the impact on CSF flow in the adjacent PVSs will also be described and quantified. The impact of these results on brain-wide models of CSF flow will also be discussed. 

Research Assistant Professor Kimberly A S Boster, University of Rochester, USA

Research Assistant Professor Kimberly A S Boster, University of Rochester, USA

09:00-09:30 Ultrasound brain tissue pulsation (BTP) in brain disorders

The recent development of ultrasound, both in probe technology and signal processing, has allowed the precise measurement of Brain Tissue Pulsations (BTP). Our team has been particularly involved in the characterization of BTP in clinical conditions. In several studies, we observed that BTP is involved in the pathophysiology of cerebrovascular diseases, cognitive and psychiatric disorders, orthostatic hypotension, normal aging, brain volume reduction, etc. Our most prolific work with BTP has focused on depression. We indeed found excessive BTP amplitudes in major depressive episode that tends to reduce with successful antidepressant treatment. In addition, we found that BTP could be used as a prognostic marker for treatment response with new generation antidepressant agent. More recent works include the technological coupling of BTP with EEG for a multimodal assessment of brain physiology in both healthy participants and patients with brain disorders. Ultrasound BTP has a high potential to being implemented in clinical routine because it is portable, non-invasive, easily accessible and low cost. However, BTP has also limitations and further clarifications in both the technique itself and in the experimental studies are required. 

Professor Thomas Desmidt, University Hospital of Tours, France

Professor Thomas Desmidt, University Hospital of Tours, France

09:45-10:15 Measuring BTP with Trans-cranial Tissue Doppler

Healthy brain tissue pulsations (BTPs) are known to occur with every cardiac cycle. In this talk, the development of Brain Tissue Velocimetry (Brain TV), a novel transcranial tissue Doppler (TCTD) ultrasound prototype, will be presented. Brain TV was created in collaboration with Nihon Kohden, Japan, and monitors brain tissue motion over the cardiac cycle. Brain TV is a portable system that can record BTPs in real-time, from multiple positions on the head, using 2 MHz transcranial Doppler (TCD) probes, together with other synchronised physiological measurement data, such as blood pressure, heart rate, and end-tidal carbon dioxide. Using Brain TV, it was possible to record BTPs from up to 30 sample depths within the brain, ranging from 22 to 80 mm below the probe’s surface, in ultrasound phantom brain models, healthy volunteer studies, and in stroke patients. This presentation will illustrate the use of the device, summarise results and insights obtained in past studies, and present the ideas behind current and future studies.

Miss Jennifer Nicholls, University of Leicester, UK

Miss Jennifer Nicholls, University of Leicester, UK

10:30-11:00 Break
11:00-11:30 Brain ultrasonology in acute brain injured patients

Brain ultrasonology stands out as a valuable diagnostic tool due to its non-invasive nature and real-time imaging capabilities, making it an efficient method for evaluating cerebral blood flow dynamics and detecting various pathologies promptly. By offering quick and bedside assessments, this technology enables healthcare professionals to make rapid decisions and interventions that can significantly impact patient outcomes.
In light of these advantages, this talk aims to further delve into the potential applications and benefits of brain ultrasonology in clinical practice. Discussing this topic can enhance our understanding of how this tool can empower healthcare providers to optimize patient care and improve outcomes, especially in situations where time is of the essence.
This presentation will delve deeper into the importance of brain ultrasonology as a rapid and bedside tool for gaining insights into cerebral dynamics. Such a discussion could not only raise awareness about the capabilities of this technology but also foster dialogue on how we can leverage its advantages to enhance patient care.

Associate Professor Chiara Robba, Policlinico San Martino, University of Genoa, Italy

Associate Professor Chiara Robba, Policlinico San Martino, University of Genoa, Italy

11:45-12:15 Ultrasound elastography during neurosurgery

Neurosurgery is a complex and intricate procedure that benefits from intraoperative guidance. During tumour resection for example, a surgeon will subjectively evaluate tumour stiffness and adherence to surrounding normal brain, using the information to optimise the resection procedure and achieve maximal resection. The outcomes for the patient, for both brain tumour and focal epilepsy surgery, depend on the extent of resection. Magnetic resonance imaging (MRI) and x-ray computed tomography provide valuable information but have not solved this problem, lacking the real-time feedback needed for intraoperative decision making. Ultrasound elastography is a promising tool that may improve a surgeon’s appreciation of tissue properties during surgery. Various forms of ultrasound elastography have been explored over the past 20-25 years. These include passive methods which use the brain’s natural pulsations, strain imaging which employs hand-induced palpation, and shear wave elastography which watches the progression of shear waves initiated by acoustic radiation force. Findings from research with these methods suggest that ultrasound elastography can effectively differentiate tumours and other lesions from healthy brain (in some cases when MRI is negative), determine the degree of adherence between tumour and brain, locate cleavage plains, and enhance the detection of residual tumour for increasing the completeness of resection. The method has considerable potential for further development and holds promise in neurosurgery, providing real-time information on tissue properties and enhancing surgical decision-making to improve safety and outcomes for patients.

Professor Jeff Bamber, Institute of Cancer Research, UK

Professor Jeff Bamber, Institute of Cancer Research, UK

Chair

Dr Jatinder S Minhas, University of Leicester, UK

Dr Jatinder S Minhas, University of Leicester, UK

13:30-14:00 Digital twins of the brain and in-silico clinical trials

Digital twins, a term often used in engineering, aim to develop computer simulations of a real-world object such that the digital twin of the object can predict what will happen to the object in the future. Increasingly, this concept is being applied with humans (or aspects of their physiology) as the object to be simulated. This allows us to better understand how to treat an individual, leading to personalised healthcare, and improved patient outcomes. Furthermore, it is hoped such an approach to healthcare can lead to a greater focus on preventative medicine to ensure people live healthier lives. From this concept, there also arises the concept of in silico clinical trials, or clinical trials that are run entirely on a computer using digital twins of humans. The development of this technology will allow for quicker, cheaper clinical trials reducing drug and medical device costs, lowering the economic burden of healthcare.

In his talk Dr El-Bouri will explain the field of digital twins and, its sister application, in silico clinical trials. Focusing on the brain vasculature, Dr El-Bouri will demonstrate how digital twins can help improve personalisation of interventions and improve the development of drugs and medical devices. Beyond the brain, Dr El-Bouri will introduce digital twins of the eye as an exciting avenue to explore ‘the pulsing brain’ in silico.

Dr Wahbi K El-Bouri, University of Liverpool, UK

Dr Wahbi K El-Bouri, University of Liverpool, UK

14:15-14:45 Hemodynamics and solute exchange in personalised brain models

Intracranial dynamics concerns physical, chemical and biological interactions between cerebral vasculature, cerebrospinal fluid (CSF) and the brain cells. Despite progress in medical imaging, organ wide patterns of fluid and solute exchange between blood, CSF and neural tissue in normal and especially pathological states remain inadequately quantified; key principles of transport and control functions of brain metabolism are still poorly understood. We propose to harness predictive mathematical models informed by dynamic imaging data to close existing knowledge gaps in cerebral blood flow and CSF dynamics. We outline mathematical models of the cerebral circulation using graph theoretical approaches. We predict blood flow patterns across multiple length scales from large blood vessels down to individual capillaries in digital analogues of mouse and human brains. Digital twins of the mouse and human brains are constructed by fusing subject-specific medical image data with hemodynamically inspired network synthesis methods. Our mechanistic modelling approach provides a rigorous platform for translating in vivo imaging observations from animals to humans and between individual subjects. The impact of these experimental and computational results on neurodegenerative diseases including dementia, Alzheimer’s disease and hydrocephalus will be highlighted. We will also show clinically relevant applications concerning the quantification of solute dispersion after intrathecal drug administration.

Professor Andreas A Linninger, University of Illinois, USA

Professor Andreas A Linninger, University of Illinois, USA

15:00-15:30 Break
15:30-16:00 Closing remarks
16:00-17:00 Open discussion: Future directions