Circuit Diagrams

In this U01 grant we propose a 5 year engineering development effort to advance Magnetic Particle Imaging (MPI) to replace MRI as the next-generation functional brain imaging tool for human neuroscience. MPI is a young but extremely promising technology that uses the non-linear magnetic response of ironoxide nanoparticles to localize their presence in the body. MPI directly detects the nanoparticle's magnetization rather than using secondary effects on the Magnetic Resonance relaxation times.

ABSTRACT: The strategic plan of the

Magnetic resonance imaging (MRI), by offering the sole means of imaging human brain structure and activity with high spatial resolution, has evolved into an indispensable tool for studying brain function in health and disease. It is uniquely suited to examining the neural basis of higher order behaviors and cognition, as well as neurodegenerative and developmental disorders, for which animal models are of limited applicability. Yet, because of current experimental limitations, there is wide range of subjects and human behaviors that are completely inaccessible by MRI techniques.

SUMMARY The overarching objective of our proposal is to bring noninvasive human brain imaging into the microscale (50-500 micron isotropic) resolution in order to create a tool for studies of neuronal circuitry and network organization in the human brain. Our breakthrough technology, MR Corticography (MRCoG), represents substantial advances over existing MRI approaches. MRCoG achieves dramatic gains in spatial and temporal resolutions by focusing several different types of coil arrays on the cerebral cortex of the live human brain.

ABSTRACT The mammalian brain is an enormously complex organ with myriad cell types cohesively working together to carry out a host of intricate tasks, from motor functions, to the storing and execution of consciousness. These cell types broadly fall into neuronal and non-neuronal classifications, the latter of which substantially outnumber the former and provide the support system and maintenance for the electrically active neuronal component.

ABSTRACT Astrocytes are the most abundant glial cells in the human brain. Interactions of astrocytes with synapses via thin perisynaptic astrocytic processes are critical for proper synaptic connectivity and function. Each mouse astrocyte sends out an extensive array of processes that are estimated to contact over 100,000 synapses. The number of astrocytes and the extent of their interactions with synapses have increased throughout evolution, indicating a close link between astrocytes and cognition.

SUMMARY In order to understand how the CNS encodes, modifies, stores and retrieves information it is necessary to explore the diverse cell populations that comprise the CNS. There is an emerging consensus that the CNS cannot be satisfactorily understood solely as a collection of circuits1. One significant missing aspect in our collective strategy to comprehensively understand the CNS is the largely unmet need to understand additional cell types such as astrocytes1. Astrocytes represent around 40% of all CNS cells and are found throughout the brain.

PROJECT SUMMARY The choroid plexus (ChP) is a vital tissue located in each ventricle in the brain. The ChP is composed of two parallel sheets of epithelial cells with an intervening network of primarily non-neural cell types and vasculature. The ChP (1) produces cerebrospinal fluid (CSF) containing growth-promoting factors for the brain, (2) forms a blood-CSF barrier that gates communication between the central nervous system (CNS) and the systemic milieu, (3) provides for immune cell entry into the brain, and (4) offers an enticing framework for enhanced drug delivery.

Project Summary/Abstract: Proper function of precisely wired neural circuits depends on a close physical and functional relationship with an equally complex and overlapping vascular network. Vascular and perivascular cells are heterogeneous both within and across brain regions, and this heterogeneity is thought to underlie the functional specialization that caters to local neuronal circuitry demands.

Project Summary: While traditionally conceived as passive support elements for neuronal networks, non-neuronal brain cells are now appreciated as dynamic integral components of central nervous system (CNS) circuitry. Astrocytes, for example, serve as powerful regulators of neuronal spiking, synaptic plasticity, and brain blood flow. Similarly, microglia not only respond to a wide range of CNS perturbations, but also participate in circuit development and plasticity through the active elimination of synaptic connections.