Systems and methods for multimodal neural sensing
Inventors
Kodandaramaiah, Suhasa • Ghanbari, Leila • SCHULMAN, Daniel Sousa • McAlpine, Michael Cary • Swisher, Sarah • Donaldson, Preston
Assignees
University of Minnesota System
Publication Number
US-12350010-B2
Publication Date
2025-07-08
Expiration Date
2040-12-04
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Abstract
A system and method is provided for imaging and monitoring a tissue, such as a cerebral cortex, of a subject. Access to imaging a tissue, such as cerebral cortex, may be provided by removing a portion of a bone, such as a portion of a skull of the subject. A prosthesis, such as an optically transparent prosthesis, may be used to replace the portion of the skull removed and may be conformed to the same 3D contour of the bone that was removed. A data acquisition system, such as an imaging system, may then be affixed to the skull prosthesis and may be used to acquire image data of the tissue of the subject at high spatial and temporal resolution and without interference from intervening bone material.
Core Innovation
The invention provides a system and method for imaging and monitoring a tissue, particularly the cerebral cortex, of a subject by removing a portion of adjacent bone or connective tissue such as the skull and replacing it with an optically transparent prosthesis that conforms to the original three-dimensional contour. This prosthesis allows high spatial and temporal resolution imaging and data acquisition of the underlying tissue without interference from opaque bone material. The system can combine multiple sensing modalities including optical imaging and electrical sensing to acquire detailed data of neuronal and cortical activity.
The problem addressed arises from the current limitations in neuroscience tools, which either provide single-cell resolution over small regions or lower resolution over large brain areas, but not both simultaneously. Additionally, existing imaging techniques are limited by head fixation or interference from bone, which restrict behavioral studies and reduce the ability to monitor complex, large-scale brain activity over time. There is also a need for improved approaches to monitor traumatic brain injury (TBI) pathology longitudinally across multiple spatial and temporal scales within the same subjects.
The disclosed solution integrates a computer system to generate contours of bone or connective tissue from images, a three-dimensionally conforming optically transparent prosthesis to replace the excised bone, and imaging and/or electrophysiological acquisition systems affixed to the prosthesis. This includes novel manufacturing of transparent cranial windows with integrated electrode arrays and miniaturized head-mounted imaging devices capable of wide-field and cellular resolution imaging in freely moving subjects. The system also supports inclusion of additional sensors, waveguides, or microfluidics, enhancing functional monitoring and intervention capabilities.
Claims Coverage
The patent includes two independent system claims covering apparatuses for acquiring data from tissue of a subject using a conforming prosthesis and imaging system, and independent method claims for performing the same function. The claims capture inventive features around the prosthesis design, data acquisition systems, electrode arrays, and integrated sensor fabrication.
System with contour-conforming prosthesis and integrated imaging system
A system comprising a computer system that accesses images of bone or connective tissue adjacent to tissue, generates a contour, and utilizes a prosthesis conforming to and replacing the contoured bone. An imaging system with sensors is affixed to the prosthesis to acquire data from the tissue.
Integration of optically transparent electrode arrays with prosthesis
A plurality of electrodes attached to the prosthesis forming an electrocorticography (ECoG) array where the combination is optically transparent, enabling simultaneous optical and electrical recordings.
Incorporation of diverse sensor and delivery mechanisms
The prosthesis may include additional sensors, waveguides, or microfluidic channels that are fabricated by techniques including 3D printing or inkjet printing, enabling monitoring of neurotransmitter concentrations or blood oxygenation.
Use of biocompatible insulating coatings on electrode arrays
Conductive traces in the electrode arrays are encapsulated with a biocompatible insulating coating with exposed sensing electrodes, where the coating material is selected based on stability of electrode impedances.
Lightweight, miniaturized imaging systems
The imaging system is removably affixed to the prosthesis and designed to have a weight less than approximately 15% of the subject's bodyweight to permit free behavior.
Prosthesis fabricated via 3D printing and polymer films
The prosthesis is formed using 3D printing and includes biocompatible polymer films such as polyethylene terephthalate (PET) that provide optical transparency and structural conformance.
The independent claims collectively cover a novel system and method for tissue imaging using a custom-shaped, optically transparent prosthesis integrated with multi-modal sensing capabilities including optical and electrical modalities, fabricated through advanced printing techniques, and designed for chronic, high-resolution monitoring in freely behaving subjects.
Stated Advantages
Enables high spatial and temporal resolution imaging and monitoring of brain tissue without interference from bone.
Allows simultaneous wide-field optical imaging and electrocorticography (ECoG) recordings in freely moving subjects.
Facilitates chronic longitudinal imaging and recording to study dynamic neural activity and morphological changes over extended periods.
Integrates multi-modal sensing (optical and electrical) that bridges the gap between single-cell and large-scale brain region monitoring.
Custom prostheses conform to the natural 3D skull contour mitigating brain tissue deformation.
Manufacturing flexibility from 3D printing and printable electronics allows rapid prototyping and customization.
Miniaturized, lightweight head-mounted imaging devices support complex behavioral paradigms not possible with head fixation.
Documented Applications
Wide-field optical and electrical imaging of cerebral cortical activity in rodents during free behavior and complex tasks such as novel object recognition and spatial exploration.
Longitudinal multi-scale monitoring of mild traumatic brain injury (mTBI) effects including neuronal activity changes, structural alterations, and behavior correlation in awake, freely moving animals.
Mapping of motor cortex dynamics in non-human primates using head-mounted microscopes and cranial windows for cellular resolution imaging.
Monitoring extracellular glutamate release dynamics and neurochemical activity during natural sleep-wake cycles.
Integration of microfluidic channels and photonic waveguides for simultaneous pharmacological and optogenetic interventions alongside imaging.
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