Multifocal Macroscope Imaging Neural Activity

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Solution Overview

Problem

Current methods for studying distributed neural processes, such as those in the mammalian cerebral cortex, are limited by the inability to simultaneously measure fast neuronal activity dynamics at cellular resolution across three-dimensional centimeter-scale fields of view, with existing techniques offering either low temporal rates or low spatial resolution.

Innovation Solution

A macroscope configured for synchronous multifocal optical imaging using a multifocal widefield optics system with a dual-focus array of lenses, capable of focusing on multiple planes, allowing for high-speed imaging of neuronal activity across large fields of view with near-cellular resolution.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If large field of view two-photon microscopes are used for simultaneous recording from cortical areas at single-cell resolution, then spatial resolution is improved, but acquisition speed deteriorates (low temporal rates)

Engineering Contradiction:
Improvespatial resolutionVSAvoidacquisition speed
Core Design Contradiction:
Measurement precisionVSProductivity

Solution Approach 1:

The imaging system is segmented into multiple focal planes using a dual-focus lenslet array, allowing simultaneous imaging of multiple cortical depths. This segmentation enables the system to capture neural activity across different layers concurrently, improving temporal resolution without sacrificing spatial detail at any single plane.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system transitions from single-plane imaging to multi-plane volumetric imaging by adding the depth dimension through focal plane multiplication. The dual-focus lenslet array creates distinct focal sheets at different depths, enabling three-dimensional neural activity recording that captures both spatial and temporal dynamics simultaneously.

Inventive Principle:
Principle #17Another dimension (Dimensionality change)

2Area of stationary object

If widefield imaging is used to reveal cortex-wide task involvement and activity patterns, then field of view is improved, but spatial resolution deteriorates (low spatial resolution)

Engineering Contradiction:
Improvefield of viewVSAvoidspatial resolution
Core Design Contradiction:
Area of stationary objectVSMeasurement precision

Solution Approach 1:

The widefield view is segmented into multiple focal planes, with each plane providing high-resolution imaging of a specific cortical depth. The lenslet array divides the incoming light into multiple focal regions, allowing the system to maintain large field of view while achieving cellular resolution at each depth plane simultaneously.

Inventive Principle:
Principle #1Segmentation

Solution Approach 2:

The system merges multiple high-resolution images from different focal planes into a comprehensive volumetric representation of cortical activity. By combining the spatial information from each plane, the system achieves both wide field of view coverage and high spatial resolution throughout the cortical volume.

Inventive Principle:
Principle #5Merging (Combining)

3Device complexity

If conventional single-focus imaging is used, then device complexity is low, but the ability to capture three-dimensional neural activity simultaneously deteriorates

Engineering Contradiction:
Improveoptical system simplicityVSAvoidmulti-plane imaging capability
Core Design Contradiction:
Device complexityVSAdaptability or versatility

Solution Approach 1:

The dual-focus lenslet array is a passive optical element that automatically creates multiple focal planes without requiring active control mechanisms. The system self-organizes the light paths through the lenslet array to produce simultaneous multi-plane imaging, eliminating the need for complex mechanical scanning or electronic control systems.

Inventive Principle:
Principle #25Self-service

Solution Approach 2:

The system replaces complex mechanical scanning systems with a static lenslet array that optically divides the field into multiple focal planes. This substitution eliminates moving parts and complex control electronics while achieving multi-plane imaging capability through pure optical means.

Inventive Principle:
Principle #28Mechanics substitution (Replace mechanical system)

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

Enables simultaneous recording of neural activity across the entire dorsal cortex at high speeds, revealing localized and distributed population encoding of motor actions and history-guided motor plans, with improved signal-to-noise ratio and spatial resolution compared to conventional methods.

Implementation Method 1

a multifocal widefield optics comprising a plurality of optical components configured to focus on a plurality of planes

Methodology Applied
Scientific EffectOptical focusing: Focusing

Data Source

PatentUS11921271B2Multifocal macroscope for large field of view imaging of dynamic specimens
Publication Date: 2024.03.05 THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
  • US11921271B2 patent drawing
  • US11921271B2 patent drawing
  • US11921271B2 patent drawing

AI summary

Provided herein is a macroscope comprising an objective apparatus comprising a multifocal widefield optics comprising a plurality of optical components configured to focus on a plurality of planes. Also provided herein are methods for analyzing a three-dimensional specimen, the method comprising obtaining, via a macroscope, synchronous multifocal optical images of a plurality of planes of the three-dimensional specimen, wherein the macroscope comprises an objective apparatus comprising a multifocal widefield optics comprising a plurality of optical components configured to focus on a plurality of planes. The three-dimensional specimen can be a biological specimen, such as brain.