# Imaging tumor microenvironment by Optical Fiber-Tethered Simultaneous Lifetime-resolved Autofluorescence-Multiharmonic (OFT-SLAM) microscopy

> **NIH NIH R01** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2020 · $398,300

## Abstract

Summary
A label-free imaging technology is proposed for general cancer research, termed as Optical Fiber-Tethered
Simultaneous Lifetime-resolved Autofluorescence and Multiharmonic (OFT-SLAM) microscopy, to overcome the
lack of a versatile tool to simultaneously visualize tumor and non-tumor cells in authentic tumor microenvironment.
The non-tumor cells broadly include the fibroblastic cells, angiogenic vascular cells, and infiltrating immune cells
that engage normal biological functions such as embryonic/adult development and inflammatory/immune
response (e.g. wound healing). However, in the tumor microenvironment where the overall metabolism is known
to switch from energy consumption to proliferative biosynthesis (the Warburg effect), these normal (neutral) cells
have all been recently recognized as the accessories to the crime (cancer). Thus, the proposed development of
this imaging technology will interrogate the interrelations between metastatic tumor cells (principal) and various
non-tumor cells (accessories) that conspire to kill a cancer patient (crime). This interrogation will be more
comprehensive than imaging-based cancer research that has typically focused on one specific cell type of
interest (the principal or one accessory of the crime). Without a label-free imaging technology like OFT-SLAM to
avoid cell-specific labeling, simultaneous visualization of various cells would perturb the tumor microenvironment
by exogenous staining, cell/tissue transplantation, and genetic modification.
We will build the “SLAM” of OFT-SLAM based on multimodal multiphoton microscopy and fluorescence-lifetime
imaging, and invoke general intrinsic contrasts of cellular optical heterogeneity and metabolic activity to reveal
and differentiate tumor and non-tumor cells. We will then empower the “SLAM” with the “OFT” to flexibly access
different anatomical sites in intravital animal/preclinical microscopy and ex vivo human/clinical histopathology.
We will subsequently employ the resulting OFT-SLAM to image the formalin-fixed human specimens of breast
cancer from Cooperative Human Tissue Network (CHTN), including the primary breast tumors, breast cancer-
induced lung and brain metastases, and surrounding peri-tumoral fields at different stages from different patients
(n > 200). In parallel, we will apply OFT-SLAM to long-term (imaging window-assisted) intravital microscopy of
three prototypical breast cancer rat/mouse models, covering all known steps throughout the invasion-metastasis
cascade. With the unique capability of OFT-SLAM to bridge otherwise isolated ex vivo human histopathology
(snapshots taken by pathologists in a clinical setting) and intravital animal microscopy (movies acquired by
biologists in a laboratory), we will strive to identify various cancer-associated cells and their interrelations in an
evolving tumor microenvironment and their dependence on spatial heterogeneity and individual variability. The
successful outcome of this project will de...

## Key facts

- **NIH application ID:** 9996554
- **Project number:** 5R01CA241618-02
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Stephen A Boppart
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $398,300
- **Award type:** 5
- **Project period:** 2019-08-15 → 2023-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9996554

## Citation

> US National Institutes of Health, RePORTER application 9996554, Imaging tumor microenvironment by Optical Fiber-Tethered Simultaneous Lifetime-resolved Autofluorescence-Multiharmonic (OFT-SLAM) microscopy (5R01CA241618-02). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/9996554. Licensed CC0.

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