In vivo Immunofluorescence-Optical Coherence Tomography

Introduction

Current clinical medicine relies on MRI and CT for structural imaging, and immuno-PET/SPECT for molecular specificity. The combination of structural imaging and molecular specific imaging provides detailed information about the expression of proteins and cell surface receptors in vivo in humans. PET-CT/MRI has become an essential component of personalized medicine.

Limitations of Current Technologies

However, the resolution of MRI/CT is just under a millimeter, while the resolution of PET is limited to about 2-10 millimeters, which is insufficient for early disease detection. Moreover, PET is associated with radiation burden from ligands labeled with a radiotracer and can image only one labeled ligand at a time.

Proposed Solution

What is missing is the ability to image in vivo with much higher resolution and to image multiple molecular targets and molecular interactions simultaneously. I propose to develop the optical equivalent of PET-CT/MRI with a 10 to 100 fold better resolution.

Methodology

To reach this goal, I will integrate three-dimensional endoscopic Optical Coherence Tomography (OCT) for structural information with depth-resolved imaging of fluorescently labeled monoclonal antibodies for molecular specificity.

Development of Immuno-OCT Technology

To image the hollow organs accessible by endoscopy, I will develop the immuno-OCT technology integrated with:

1. Miniature motorized catheters
2. Multi-fiber detection technology for depth-resolved fluorescence determination

This will enable endoscopic immuno-OCT in catheters as small as 1.5 mm in diameter.

Focus Areas

I will focus on esophageal cancer and lung disease.

Broader Impact

The proposed research has a much broader impact, creating a platform to study in detail therapy-tissue interactions longitudinally in vivo in patients, providing in vivo information approaching immunohistochemistry analysis.

Conclusion

This approach will revolutionize the diagnosis and treatment of patients with a resolution approaching immunohistology at high speed over large volumes using minimally invasive technologies.