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Updated: Oct 13, 2025

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A Two-Photon Microimaging-Microdevice System for Four-Dimensional Imaging of Local Drug Delivery in Tissues.

Guigen Liu¹, Veronica Valvo¹, Sebastian W Ahn¹

¹Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, 221 Longwood Ave, Boston, MA 02115, USA.

International Journal of Molecular Sciences

|November 13, 2021

Summary

This study introduces a novel microimaging-microdevice system for 4D visualization of drug delivery and tissue response within tumors. This advancement enables precise monitoring of drug concentration and its effects in real-time, crucial for cancer research.

Keywords:

biomedical microdevice in vivo testing local drug delivery optical sectioning tumors two-photon micro-endoscopy

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Spatio-Temporal In Vivo Imaging of Ocular Drug Delivery Systems using Fiberoptic Confocal Laser Microendoscopy

Spatio-Temporal In Vivo Imaging of Ocular Drug Delivery Systems using Fiberoptic Confocal Laser Microendoscopy

Published on: September 27, 2021

Area of Science:

Biomedical Engineering
Oncology
Medical Imaging

Background:

Intratumor drug response measurement has advanced with microdevices for in vivo screening.
Previous systems offered bulk measurements but lacked 3D visualization of drug distribution and tissue response.
Understanding the drug concentration-effect relationship in 3D is critical for effective cancer therapy.

Purpose of the Study:

To develop a next-generation system for high-resolution, 4D imaging of intratumor drug delivery and tissue response.
To integrate multiplexed drug release with a miniaturized two-photon micro-endoscope for continuous spatial profiling.
To overcome the limitations of previous bulk measurement techniques by enabling visualization of drug distribution and its effects within the tumor microenvironment.

Main Methods:

Integration of a miniaturized two-photon micro-endoscope with a multiplexed intratumor drug release microdevice.
Development of a microimaging-microdevice (MI-MD) system for continuous 3D spatial imaging.
Utilizing optical sectioning for profiling the tumor microenvironment adjacent to the microdevice over time.

Main Results:

Successful demonstration of four-dimensional (3D space + time) imaging of local drug delivery.
Validation of the MI-MD system in both tissue phantoms and live tumors.
Establishment of a method to visualize drug distribution and concurrent tissue responses in situ.

Conclusions:

The novel MI-MD system provides unprecedented 4D visualization of drug delivery and tissue response within tumors.
This technology enables detailed study of the relationship between drug concentration and therapeutic effect.
Future applications include investigating drug resistance mechanisms and immune cell responses to anti-cancer agents in live organisms.