# Super-resolution chemical imaging via a diffusion-based deep generative model

> **NIH NIH R21** · UNIVERSITY OF WASHINGTON · 2024 · $196,182

## Abstract

Project Summary/Abstract
 The overarching objective of this project is to develop an advanced computational super-resolution model to
enhance the throughput and resolution of chemical imaging. Chemical imaging, which includes advanced
techniques such as stimulated Raman scattering (SRS) microscopy, holds immense potential in intraoperative
cancer detection. This is due to its ability to generate intrinsic molecular contrasts without tissue processing or
labeling, which can improve the accuracy and speed of intraoperative diagnosis. Such improvement is crucial to
better patient outcomes by providing near real-time feedback to the surgeon and reducing the risk of leftover
cancerous tissues. However, existing chemical imaging techniques grapple with an inherent limitation – the
tradeoff between spatial resolution and imaging field of view, resulting in low imaging throughput and prolonged
imaging durations for larger tissue samples. For other applications involving live cell imaging, the limited
resolution of SRS (> 300nm) hinders visualization of subcellular organelles and fine structures.
 Computational super-resolution, bolstered by advancements in artificial intelligence, can address these
challenges by transforming low-resolution images into high-resolution versions. This has been achieved with the
Convolutional Neural Network and the Generative Adversarial Network. However, super-resolution chemical
imaging is scarce. There are no datasets available for super-resolution training. It is also unclear whether existing
super-resolution microscopy techniques could work for chemical images due to vast differences in imaging
contrasts. Here we propose to develop a new super-resolution technique ChemDiffuse that is based on the
diffusion-based deep generative network. Diffusion-based models are widely used in popular image-generation
tools such as Midjourney and DALL-E. While superior in stability and image quality to CNN and GAN models,
they need extensive training data. Leveraging on our recent progress in image augmentation and a new diffusion
model for 2D and 3D data, we will develop the ChemDiffuse model to significantly improve SRS imaging
throughput and resolution. We aim to test the application of the ChemDiffuse super-resolution model in two
different areas: 1. Fast gigapixel SRS imaging of tissue at submicron resolution for pathology application. We
will use mouse brain tissue as our test system to train the ChemDiffuse model to enable fast 3D SRS imaging at
10 million pixels/sec, a 40-fold improvement in lateral dimension, and another 10-fold improvement in axial
dimensional. Such improvement is crucial for intraoperative stimulated Raman histology of large tissues. 2.
Label-free SRS imaging of live cell organelles at 150 nm resolution. We will train the super-resolution model to
enable 2-fold resolution enhancement with regular SRS imaging, an improvement that will allow unprecedented
label-free tracking of multiple organelles and single c...

## Key facts

- **NIH application ID:** 10948861
- **Project number:** 1R21EB036205-01
- **Recipient organization:** UNIVERSITY OF WASHINGTON
- **Principal Investigator:** Dan Fu
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $196,182
- **Award type:** 1
- **Project period:** 2024-08-01 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10948861

## Citation

> US National Institutes of Health, RePORTER application 10948861, Super-resolution chemical imaging via a diffusion-based deep generative model (1R21EB036205-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10948861. Licensed CC0.

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