Biological Sample EDF Imaging That Preserves Cell Spatial Relationships
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Solution Overview
Problem
Conventional extended depth of focus (EDF) systems fail to preserve the spatial relationship between objects on different planes in semi-transparent biological specimens, leading to incorrect diagnoses by blurring or crowding cells and altering magnification, which can misrepresent the tissue architecture and introduce artifacts like staircase edges.
Innovation Solution
An enhanced EDF system that identifies optimal focal planes for different segments of a biological sample, preserving the spatial relationship between cells by deemphasizing underlying objects and generating a composite image that maintains the correct focus on diagnostically important features.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Length of stationary object
If conventional EDF systems are used to extend depth of focus, then more of the specimen can be viewed, but the spatial relationship between objects on different planes is lost and artifacts are introduced
Solution Approach 1:
The patent processes image stacks along the z-axis (depth dimension) to generate an EDF image that preserves spatial relationships. By analyzing focus metrics across multiple focal planes and selectively combining in-focus pixels while maintaining their z-position information, the system extends depth of field without losing the three-dimensional spatial arrangement of cells and tissue structures.
Solution Approach 2:
The patent applies local quality assessment by evaluating focus metrics for individual pixels or regions across multiple focal planes. Each pixel's contribution to the final EDF image is determined by its local focus quality, allowing the system to selectively enhance in-focus regions while maintaining the spatial relationships of out-of-focus regions, thereby preserving overall spatial accuracy while extending usable depth.
2Length of stationary object
If conventional EDF systems combine pixels from different focal planes, then extended depth is achieved, but magnification changes and staircase artifacts are introduced
Solution Approach 1:
The patent employs dynamic focus adjustment by automatically determining the optimal focal plane for each region of the specimen based on focus metrics. The system dynamically selects which pixels from which focal planes to include in the EDF image, adapting to local variations in specimen thickness and cell position, thereby eliminating staircase artifacts and maintaining consistent magnification perception.
Solution Approach 2:
The patent uses focus metrics as feedback to guide the EDF image construction process. By calculating sharpness or focus quality measures for pixels across multiple focal planes and using this feedback to selectively combine only the most in-focus pixels, the system achieves extended depth of field while maintaining high image accuracy and avoiding artifacts introduced by arbitrary pixel combination.
3Measurement precision
If pathologists manually refocus to view thick specimens, then all focal planes can be examined, but productivity decreases and subtle features may be missed
Solution Approach 1:
The patent performs preliminary automated analysis by processing the entire image stack to generate an EDF image that presents all in-focus features across the specimen thickness in a single composite view. This preliminary processing allows pathologists to immediately assess the entire specimen without manual refocusing, rapidly identifying regions of interest while preserving detection accuracy for subtle diagnostic features.
Solution Approach 2:
The patent creates a two-dimensional EDF copy or representation of the three-dimensional specimen that preserves all diagnostically relevant in-focus features. This EDF copy serves as a comprehensive overview that maintains the accuracy needed for diagnosis while eliminating the time-consuming manual refocusing process, thereby significantly improving productivity without sacrificing detection capability.
Data Source
AI summary
A system and method for constructing a digital composite image of a three-dimensional biological sample. The system includes an optical system that captures images of cells and tissue presented on a specimen slide. The system systematically acquires a stack of images at different segments across the specimen slide. For each segment, the system dynamically calculates an optimal focal plane. Once an optimal focal plane is determined for each of the stacks of images, the system generates a composite image by copying the sharpest objects from each of the optimal focal planes.