Neuron Mapping via Temporal Photon Correlation

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Solution Overview

Problem

Current methods for imaging calcium channel activity in deep brain tissue face significant challenges due to light scattering, leading to low spatial resolution and inability to directly access neurons, limiting understanding of brain function and health.

Innovation Solution

A system utilizing a light source, optical filter, and image capture device, coupled with a processor that generates a 3D geometric spatial and temporal model to map neuron activity by filtering out initial light wavelengths and capturing emitted light at different wavelengths, allowing for precise localization of neurons through highly scattering media.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Length of stationary object

If diffusive optical imaging methods are used for deep tissue imaging, then imaging depth is improved, but spatial resolution deteriorates due to strong attenuation of high-frequency information

Engineering Contradiction:
Improveimaging depthVSAvoidspatial resolution
Core Design Contradiction:
Length of stationary objectVSMeasurement precision

Solution Approach 1:

The system uses time-resolved detection to capture the temporal profile of photon arrival, exploiting the periodic nature of light propagation through tissue. By analyzing the time distribution of detected photons, the system can distinguish between photons that traveled different path lengths through scattering media, thereby recovering spatial information that would otherwise be lost in diffusive imaging.

Inventive Principle:
Principle #19Periodic action

Solution Approach 2:

The invention changes the parameter being measured from spatial distribution alone to temporal distribution of photon arrival. This parameter transformation allows the system to encode spatial frequency information in the temporal domain, overcoming the fundamental limitation of diffusive imaging where spatial resolution degrades with depth.

Inventive Principle:
Principle #35Parameter changes

2Measurement precision

If conventional optical imaging methods are used, then direct access to neurons is improved, but imaging depth deteriorates due to light scattering in deep tissue

Engineering Contradiction:
Improveneuron detection accuracyVSAvoidimaging depth
Core Design Contradiction:
Measurement precisionVSLength of stationary object

Solution Approach 1:

The system uses temporal correlation analysis as an intermediary process to bridge the gap between scattered light detection and neuron localization. By computing the correlation between measured temporal photon distributions and modeled distributions from candidate neuron positions, the system can accurately identify neuron locations even when direct optical paths are scattered.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention replaces direct optical mechanical imaging with a computational correlation-based approach. Instead of relying on optical focusing and direct line-of-sight imaging, the system uses temporal point spread function correlation to computationally reconstruct neuron positions from scattered light measurements, substituting mechanical optical precision with computational analysis.

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

3Reliability

If fMRI with BOLD contrast is used, then brain signaling measurement is improved, but spatial resolution and temporal resolution deteriorate due to indirect blood oxygen level measurement

Engineering Contradiction:
Improvebrain signaling measurementVSAvoidspatial and temporal resolution
Core Design Contradiction:
ReliabilityVSMeasurement precision

Solution Approach 1:

The system extracts direct optical signals from neurons by detecting fluorescence emission at specific wavelengths that are characteristic of neuronal calcium indicators. By filtering out non-specific signals and isolating the wavelength-specific fluorescence emission, the system obtains direct neuronal activity measurements rather than indirect hemodynamic responses.

Inventive Principle:
Principle #2Taking out (Extraction)

Solution Approach 2:

The invention creates a multi-functional imaging system that can simultaneously provide deep tissue penetration, high spatial resolution for neuron localization, and high temporal resolution for calcium dynamics measurement. This universal system replaces the need for separate fMRI and optical imaging systems by integrating the advantages of both approaches.

Inventive Principle:
Principle #6Universality (Multi-functionality)

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 high-resolution imaging of neurons deep within the brain, overcoming the limitations of existing methods by providing spatial and temporal information on neuron activity, potentially offering new insights into brain function and neurological diseases.

Implementation Method 1

a source of light configured to be shone on a subject, the light source configured to illuminate brain tissue of a subject at a first wavelength, and in response cause emission of light at a second wavelength from generated calcium when one or more neurons are firing

Methodology Applied
Scientific EffectFluorescence: Fluorescence

Implementation Method 2

an optical filter configured to filter out light having the first wavelength and allow passage of light having the second wavelength

Methodology Applied
Scientific EffectOptical filtering: Filter (optical)

Data Source

PatentUS11751797B2System for spatial and temporal mapping of neurons in brain tissue
Publication Date: 2023.09.12 PURDUE RES FOUND
  • US11751797B2 patent drawing
  • US11751797B2 patent drawing
  • US11751797B2 patent drawing

AI summary

A system for spatially mapping neurons in brain tissue is disclosed which includes a source of light configured to be shone on a subject at a first wavelength causing emission of light at a second wavelength from generating calcium when one or more neurons are firing, an optical filter configured to allow passage of light having the second wavelength, an image capture device configured to capture images of the brain tissue at the second wavelength, and a processor with software configured to establish a spatial model for localizing one or more neurons where captured images are used to iteratively adjust parameters of the model to thereby minimize error between generated and captured images.