In vivo Immunofluorescence-Optical Coherence Tomography

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 expression of proteins and cell surface receptors in vivo in humans. PET-CT/MRI has become an essential component of personalized medicine.

However, the resolution of MRI/CT is just under a millimeter, while the resolution of PET is limited to about 2-10 millimeters, insufficient for early disease detection.

Moreover, PET is associated with radiation burden of ligands labeled with a radiotracer and can image only one labeled ligand at a time.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.

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.

To image the hollow organs accessible by endoscopy, I will develop the immuno-OCT technology integrated with miniature motorized catheters and the multi-fiber detection technology for depth resolved fluorescence determination for endoscopic immuno-OCT in catheters as small as 1.5 mm diameter. I will focus on esophageal cancer and lung disease.

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.

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.