Aaron D. Aguirre

In vivo diagnosis of plaque erosion and calcified nodule in patients with acute coronary syndrome by intravascular optical coherence tomography.

OBJECTIVES The aim of this study was to characterize the morphological features of plaque erosion and calcified nodule in patients with acute coronary syndrome (ACS) by optical coherence tomography (OCT). BACKGROUND Plaque erosion and calcified nodule have not been systematically investigated in vivo. METHODS A total of 126 patients with ACS who had undergone pre-intervention OCT imaging were included. The culprit lesions were classified as plaque rupture (PR), erosion (OCT-erosion), calcified nodule (OCT-CN), or with a new set of diagnostic criteria for OCT. RESULTS The incidences of PR, OCT-erosion, and OCT-CN were 43.7%, 31.0%, and 7.9%, respectively. Patients with OCT-erosion were the youngest, compared with those with PR and OCT-CN (53.8 ± 13.1 years vs. 60.6 ± 11.5 years, 65.1 ± 5.0 years, p = 0.005). Compared with patients with PR, presentation with non-ST-segment elevation ACS was more common in patients with OCT-erosion (61.5% vs. 29.1%, p = 0.008) and OCT-CN (100% vs. 29.1%, p < 0.001). The OCT-erosion had a lower frequency of lipid plaque (43.6% vs. 100%, p < 0.001), thicker fibrous cap (169.3 ± 99.1 μm vs. 60.4 ± 16.6 μm, p < 0.001), and smaller lipid arc (202.8 ± 73.6° vs. 275.8 ± 60.4°, p < 0.001) than PR. The diameter stenosis was least severe in OCT-erosion, followed by OCT-CN and PR (55.4 ± 14.7% vs. 66.1 ± 13.5% vs. 68.8 ± 12.9%, p < 0.001). CONCLUSIONS Optical coherence tomography is a promising modality for identifying OCT-erosion and OCT-CN in vivo. The OCT-erosion is a frequent finding in patients with ACS, especially in those with non-ST-segment elevation ACS and younger patients. The OCT-CN is the least common etiology for ACS and is more common in older patients. (The Massachusetts General Hospital Optical Coherence Tomography Registry; NCT01110538).

Micromotor endoscope catheter for in vivo, ultrahigh-resolution optical coherence tomography

A distally actuated, rotational-scanning micromotor endoscope catheter probe is demonstrated for ultrahigh-resolution in vivo endoscopic optical coherence tomography (OCT) imaging. The probe permits focus adjustment for visualization of tissue morphology at varying depths with improved transverse resolution compared with standard OCT imaging probes. The distal actuation avoids nonuniform scanning motion artifacts that are present with other probe designs and can permit a wider range of imaging speeds. Ultrahigh-resolution endoscopic imaging is demonstrated in a rabbit with <4-microm axial resolution by use of a femtosecond Cr:forsterite laser light source. The micromotor endoscope catheter probe promises to improve OCT imaging performance in future endoscopic imaging applications.

High-resolution optical coherence microscopy for high-speed, in vivo cellular imaging

Optical coherence microscopy (OCM) is demonstrated with a high-speed, broadband, reflective-grating phase modulator and a femtosecond Ti:Al2O3 laser. The novel system design permits high-resolution OCM imaging in a new operating regime in which a short coherence gate is used to relax the requirement for high-numerical-aperture confocal axial sectioning. In vivo cellular imaging is demonstrated in the Xenopus laevis tadpole and in human skin with a 3-microm coherence gate and a 30-microm confocal gate. The ability to achieve cellular imaging with a lower numerical aperture should facilitate the development of miniaturized probes for in vivo imaging applications.

Macrophages Facilitate Electrical Conduction in the Heart

Organ-specific functions of tissue-resident macrophages in the steady-state heart are unknown. Here, we show that cardiac macrophages facilitate electrical conduction through the distal atrioventricular node, where conducting cells densely intersperse with elongated macrophages expressing connexin 43. When coupled to spontaneously beating cardiomyocytes via connexin-43-containing gap junctions, cardiac macrophages have a negative resting membrane potential and depolarize in synchrony with cardiomyocytes. Conversely, macrophages render the resting membrane potential of cardiomyocytes more positive and, according to computational modeling, accelerate their repolarization. Photostimulation of channelrhodopsin-2-expressing macrophages improves atrioventricular conduction, whereas conditional deletion of connexin 43 in macrophages and congenital lack of macrophages delay atrioventricular conduction. In the Cd11bDTR mouse, macrophage ablation induces progressive atrioventricular block. These observations implicate macrophages in normal and aberrant cardiac conduction.

Two-axis MEMS Scanning Catheter for Ultrahigh Resolution Three-dimensional and En Face Imaging

Ultrahigh resolution two and three-dimensional optical coherence tomography (OCT) imaging was performed using a miniaturized, two-axis scanning catheter based upon microelectromechanical systems (MEMS) mirror technology. The catheter incorporated a custom-designed and fabricated, 1-mm diameter MEMS mirror driven by angular vertical comb (AVC) actuators on both an inner mirror axis and an outer, orthogonal gimbal axis. Using a differential drive scheme, a linearized position response over +/- 6 degrees mechanical angle was achieved. The flexible, fiber-optic catheter device measured < 5 mm in outer diameter with a rigid length of ~ 2.5 cm at the distal end. In vivo and ex vivo images are presented with < 4 microm axial and ~ 12 microm transverse resolution in tissue.

Continuum generation in a novel photonic crystal fiber for ultrahigh resolution optical coherence tomography at 800 nm and 1300 nm

Ultrahigh resolution optical coherence tomography (OCT) is demonstrated at 800 nm and 1300 nm using continuum generation in a single photonic crystal fiber with a parabolic dispersion profile and two closely spaced zero dispersion wavelengths. Both wavelengths are generated simultaneously by pumping the fiber with ~78 mW average power at 1064 nm in a 52 MHz, 85 fs pulse train from a compact Nd:Glass oscillator. Continuum processes result in a double peak spectrum with > 110 nm and 30 mW average power at 800 nm and > 150 nm and 48 mW at 1300 nm. OCT imaging with < 5 mum resolution in tissue at 1300 nm and < 3 mum resolution at 800 nm is demonstrated. Numerical modeling of propagation was used to predict the spectrum and can be used for further optimization to generate smooth, broad spectra for OCT applications.

Ultrahigh resolution real time OCT imaging using a compact femtosecond Nd:Glass laser and nonlinear fiber.

Ultrahigh resolution, real time OCT imaging is demonstrated using a compact femtosecond Nd:Glass laser that is spectrally broadened in a high numerical aperture single mode fiber. A reflective grating phase delay scanner enables broad bandwidth, high-speed group delay scanning. We demonstrate in vivo, ultrahigh resolution, real time OCT imaging at 1 microm center wavelength with <5 microm axial resolution in free space (<4 microm in tissue). The light source is robust, portable, and well suited for in vivo imaging studies.

Ultrahigh resolution optical biopsy with endoscopic optical coherence tomography

Optical coherence tomography (OCT) is an emerging medical imaging technology that can generate high resolution, cross-sectional images of tissue in situ and in real time. Although endoscopic OCT has been used successfully to identify certain pathologies in the gastrointestinal tract, the resolution of current endoscopic OCT systems has been limited to 10-15 microm for in vivo studies. In this study, in vivo imaging of the rabbit gastrointestinal tract is demonstrated at a three-fold higher resolution (< 5 microm), using a broadband Cr(4+):Forsterite laser as the optical light source. Images acquired from the esophagus, trachea, and colon reveal high resolution details of tissue architecture. Definitive correlation of architectural features in OCT images and histological sections is shown. The ability of ultrahigh resolution endoscopic OCT to image tissue morphology at an unprecedented resolution in vivo advances the development of OCT as a potential imaging tool for the early detection of neoplastic changes in biological tissue.

Swept source optical coherence microscopy using a Fourier domain mode-locked laser

Swept source optical coherence microscopy (OCM) enables cellular resolution en face imaging as well as integration with optical coherence tomography (OCT) cross sectional imaging. A buffered Fourier domain mode-locked (FDML) laser light source provides high speed, three dimensional imaging. Image resolutions of 1.6 microm x 8 microm (transverse x axial) with a 220 microm x 220 microm field of view and sensitivity higher than 98 dB are achieved. Three dimensional cellular imaging is demonstrated in vivo in the Xenopus laevis tadpole and ex vivo in the rat kidney and human colon.

Integrated Optical Coherence Tomography and Microscopy for Ex Vivo Multiscale Evaluation of Human Breast Tissues

Three-dimensional (3D) tissue imaging methods are expected to improve surgical management of cancer. In this study, we examined the feasibility of two 3D imaging technologies, optical coherence tomography (OCT) and optical coherence microscopy (OCM), to view human breast specimens based on intrinsic optical contrast. Specifically, we imaged 44 ex vivo breast specimens including 34 benign and 10 malignant lesions with an integrated OCT and OCM system developed in our laboratory. The system enabled 4-μm axial resolution (OCT and OCM) with 14-μm (OCT) and 2-μm (OCM) transverse resolutions, respectively. OCT and OCM images were compared with corresponding histologic sections to identify characteristic features from benign and malignant breast lesions at multiple resolution scales. OCT and OCM provide complimentary information about tissue microstructure, thus showing distinctive patterns for adipose tissue, fibrous stroma, breast lobules and ducts, cysts and microcysts, as well as in situ and invasive carcinomas. The 3D imaging capability of OCT and OCM provided complementary information to individual 2D images, thereby allowing tracking features from different levels to identify low-contrast structures that were difficult to appreciate from single images alone. Our results lay the foundation for future in vivo optical evaluation of breast tissues, using OCT and OCM, which has the potential to guide core needle biopsies, assess surgical margins, and evaluate nodal involvement in breast cancer.