# Development of nonlinear endomicroscopy: toward assessing articular cartilage repair In vivo

> **NIH NIH P20** · CLEMSON UNIVERSITY · 2021 · $254,089

## Abstract

SUMMARY
Repair and regeneration of articular cartilage remains a clinical and scientific challenge. Reliable assessment
tools for evaluating outcomes of cartilage repair are critical for both refinement of existing methods and
development of new techniques. Histological analysis of biopsies is the gold standard for repair assessment;
however, biopsies are invasive procedures and therefore limited in clinical evaluation and studies of the
cartilage repair. The common medical imaging methods, such as x-ray radiography, computed tomography
(CT), magnetic resonance imaging (MRI), and ultrasound, can perform imaging non-destructively; however,
their spatial resolutions are not sufficient to reveal the complex cell and matrix architecture of articular cartilage.
Though some imaging techniques are non-destructive and can image tissue, such as arthroscopy, laser
scanning confocal arthroscopy (LSCA) and optical coherence tomography (OCT), they are all performed as
surgical procedures because of using thick endoscopy probes. The inability to perform clinical in vivo imaging
on cartilage tissue with high spatial resolution remains a problem. To solve the problem, we propose to
develop a nonlinear optical microscopy (NLOM) based endomicroscopy system for assessment of cartilage
repair in vivo. In NLOM imaging of cartilage tissue, second harmonic generation (SHG) signal provides high-
resolution information of fibril organization of collagen while two-photon excited fluorescence (TPEF) enables
visualization of chondrocytes and elastin fibers. However, the current cartilage NLOM imaging devices all use
tabletop systems that are too bulky to be used directly in clinical applications. Thus, our long-term goal is to
translate this technology into a clinical imaging tool for assessment of articular cartilage repair and treatment at
the cellular level. In this application, we will focus on three specific aims as follows. (1) We will determine the
efficacy of using NLOM to evaluate morphological changes of articular cartilage. Using spontaneous OA
guinea pigs as an articular cartilage pathology model, we will test if NLOM imaging can detect the quantitative
differences among the early stages of OA cartilage tissues. (2) We will design and build a compact and high-
speed NLOM imaging system with a thin rod objective as the imaging probe. A numerical simulation model will
be developed to help optimize the system design. (3) With the developed endomicroscope, we will first
evaluate its performance by performing a similar quantitative imaging study as described in Aim1 on excised
cartilage tissues from guinea pigs with OA. We will then use the endomicroscope and tabletop system to
perform a quantitative imaging study on a cartilage repair model to test if the endomicroscope can detect
morphological differences between tissues in non-treated and microfracture treated defects. With the success
of this study, we will be able to determine the usefulness and limitation for u...

## Key facts

- **NIH application ID:** 10244921
- **Project number:** 5P20GM121342-04
- **Recipient organization:** CLEMSON UNIVERSITY
- **Principal Investigator:** Tong Ye
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $254,089
- **Award type:** 5
- **Project period:** 2018-09-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10244921

## Citation

> US National Institutes of Health, RePORTER application 10244921, Development of nonlinear endomicroscopy: toward assessing articular cartilage repair In vivo (5P20GM121342-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10244921. Licensed CC0.

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