Advanced Confocal Microendoscopy Wibool Piyawattanametha, Ph.D.

High resolution subsurface imaging RESOLUTION (log) IMAGE PENETRATION (log) 1 mm 100  m 10  m 1  m ULTRASOUND MRI, CT OPTICAL COHERENCE TOMOGRAPHY  m 1 mm 1 cm 10 cm OPTICAL COHERENCE MICROSCOPY CONFOCAL MICROSCOPY TWO-PHOTON MICROSCOPY DUAL-AXES CONFOCAL MICROSCOPY

What are we trying to achieve?  Provide optical sectioning with histopathology resolution with molecular contrast in real time  Benefits: Cancer screening (sub-surface imaging): -Early detection of cancer -Aid tumor staging diagnosis Locate tumor margin/boundary Track targeted therapy etc.

“Virtual biopsy” with miniature microendoscope Handheldminiaturized 1 cm Zeiss ® 1 m Tabletop

Cancers of epithelium Malignant tissues originating from epithelial layer of organs -Epithelial layer: µm from the tissue surface Extremely common cancer: -85% of all new cancer cases Extremely deadly: -80% of all cancer deaths Examples: ovary, cervix, upper and lower GI, ENT, brain, bladder, etc.

10-mm intravital & skin scope (785-nm) 5-mm GI endoscope (785-nm) 1 cm Confocal microscope & endoscope 10-mm5-mm 5 cm

4  m MEMS scanner Microelectromechanical systems (MEMS) based microendoscope (5-mm diameter)

Assembly of a 5-mm diameter microendoscope

Ex vivo imaging of human colon Crypt lumens Colonocyte Normal Adenomatous polyps Scale bars: 100 µm

Normal squamous esophagus biopsy Vertical Section Horizontal Section (275  m deep)

Barrett’s esophagus biopsy Vertical Section Horizontal Section (200  m deep)

Real-time in vivo tumor vasculature 100 µm

Mosaicing of real-time in vivo human skin

Real-time in vivo imaging of human colon