Comprehensive volumetric microscopy of epithelial, mucosal and endothelial tissues in living human patients would have a profound impact in medicine by enabling diagnostic imaging at the cellular level over large surface areas. Considering the vast area of these tissues with respect to the desired sampling interval, achieving this goal requires rapid sampling. Although noninvasive diagnostic technologies are preferred, many applications could be served by minimally invasive instruments capable of accessing remote locations within the body. We have developed a fiber-optic imaging technique termed optical frequency-domain imaging (OFDI) that satisfies these requirements by rapidly acquiring high-resolution, cross-sectional images through flexible, narrow-diameter catheters. Using a prototype system, we show comprehensive microscopy of esophageal mucosa and of coronary arteries in vivo. Our pilot study results suggest that this technology may be a useful clinical tool for comprehensive diagnostic imaging for epithelial disease and for evaluating coronary pathology and iatrogenic effects.

14 15Exquisitely sensitive broadband detectors are needed to expand the capabilities of biomedical ultrasound, 30The sensitive detection of broadband ultrasound waves in the hundreds of kHz to tens of beam as required to achieve small element size for low directional sensitivity. 107The strong optical confinement afforded by the planoconcave microresonator design creates the opportunity 108 to maximise sensitivity in two ways. The first is by increasing the mirror reflectivity, trapping light for longer 109 and increasing the number of significant round trips in the cavity, leading to a higher Q-factor and thus a higher showing the 50% cut-off for the modelled response of a disk-shaped purely spatially averaging sensor of diameter 2mm. c, 161Directional response of 100μm sensor at selected frequencies as compared to the modelled response of a disk-shaped 162 spatially averaging receiver of diameter 2mm. For all data: w " = 12.5μm. 164Along with the NEP measurements in figure 1, the frequency response data in figure 2

Objectives We present the first clinical experience with intracoronary optical frequency domain imaging (OFDI) in human patients. Background Intracoronary optical coherence tomography (OCT) is a catheter-based optical imaging modality that is capable of providing microscopic (∼7-μm axial resolution, ∼30-μm transverse resolution), cross-sectional images of the coronary wall. Although the use of OCT has shown substantial promise for imaging coronary microstructure, blood attenuates the OCT signal, necessitating prolonged, proximal occlusion to screen long arterial segments. OFDI is a second-generation form of OCT that is capable of acquiring images at much higher frame rates. The increased speed of OFDI enables rapid, 3-dimensional imaging of long coronary segments after a brief, nonocclusive saline purge. Methods Volumetric OFDI images were obtained in 3 patients after intracoronary stent deployment. Imaging was performed in the left anterior descending and right coronary arteries with the use of a nonocclusive saline purge rates ranging from 3 to 4 ml/s and for purge durations of 3 to 4 s. After imaging, the OFDI datasets were segmented using previously documented criteria and volume rendered. Results Good visualization of the artery wall was obtained in all cases, with clear viewing lengths ranging from 3.0 to 7.0 cm at pullback rates ranging from 5 to 20 mm/s. A diverse range of microscopic features were identified in 2 and 3 dimensions, including thin-capped fibroatheromas, calcium, macrophages, cholesterol crystals, bare stent struts, and stents with neointimal hyperplasia. There were no complications of the OFDI procedure. Conclusions Our results demonstrate that OFDI is a viable method for imaging the microstructure of long coronary segments in patients. Given its ability to provide microscopic information in a practical manner, this technology may be useful for studying human coronary pathophysiology in vivo and as a clinical tool for guiding the management of coronary artery disease. (J Am Coll Cardiol Img 2008;1:752–61)