Edward L. Hull

Detection of Lipid Core Coronary Plaques in Autopsy Specimens With a Novel Catheter-Based Near-Infrared Spectroscopy System

OBJECTIVES This study sought to assess agreement between an intravascular near-infrared spectroscopy (NIRS) system and histology in coronary autopsy specimens. BACKGROUND Lipid core plaques cannot be detected by conventional tests, yet are suspected to be the cause of most acute coronary syndromes. Near-infrared spectroscopy is widely used to determine the chemical content of substances. A NIRS system has been developed and used successfully in 99 patients. METHODS Scanning NIRS was performed through blood in 212 coronary segments from 84 autopsy hearts. One histologic section was analyzed for every 2 mm of artery. Lipid core plaque of interest (LCP) was defined as a lipid core >60 degrees in circumferential extent, >200-microm thick, with a mean fibrous cap thickness <450 microm. The first 33 hearts were used to develop the algorithm; the subsequent 51 validation hearts were used in a prospective, double-blind manner to evaluate the accuracy of NIRS in detecting LCP. A NIRS-derived lipid core burden index for an entire artery was also validated by comparison to histologic findings. RESULTS The LCPs were present in 115 of 2,649 (4.3%) sections from the 51 validation hearts. The algorithm prospectively identified LCP with a receiver-operator characteristic area of 0.80 (95% confidence interval [CI]: 0.76 to 0.85). The lipid core burden index detected the presence or absence of any fibroatheroma with an area under the curve of 0.86 (95% CI: 0.81 to 0.91). A retrospective analysis of lipid core burden index conducted in extreme artery segments with either no or extensive fibroatheroma yielded an area under the curve of 0.96 (95% CI: 0.92 to 1.00), confirming the accuracy of spectroscopy in identifying plaques with markedly different lipid content under ideal circumstances. CONCLUSIONS This novel catheter-based NIRS system accurately identified lipid core plaques through blood in a prospective study in coronary autopsy specimens. It is expected that this novel capability will be of assistance in the management of patients with coronary artery disease.

A catheter-based near-infrared scanning spectroscopy system for imaging lipid-rich plaques in human coronary arteries in vivo

Although heart disease remains the leading cause of death in the industrialized world, there is still no method, even under cardiac catheterization, to reliably identify those atherosclerotic lesions most likely to lead to heart attack and death. These lesions, which are often non-stenotic, are frequently comprised of a necrotic, lipid-rich core overlaid with a thin fibrous cap infiltrated with inflammatory cells. InfraReDx has developed a scanning, near-infrared, optical-fiber-based, spectroscopic cardiac catheter system capable of acquiring NIR reflectance spectra from coronary arteries through flowing blood under automated pullback and rotation in order to identify lipid-rich plaques (LRP). The scanning laser source and associated detection electronics produce a spectrum in 5 ms at a collection rate of 40 Hz, yielding thousands of spectra in a single pullback. The system console analyzes the spectral data with a chemometric model, producing a hyperspectral image (a Chemogram, see figure below) that identifies LRP encountered in the region interrogated by the system. We describe the system architecture and components, explain the experimental procedure by which the chemometric model was constructed from spectral data and histology-based reference information collected from autopsy hearts, and provide representative data from ongoing ex vivo and clinical studies.

Optical mechanisms for detection of lipid-rich atherosclerotic plaques by near-infrared spectroscopy

InfraReDx has developed a spectroscopic cardiac catheter system capable of acquiring near-infrared (NIR) reflectance spectra from coronary arteries in vivo for identification of lipid-rich plaques of interest (LRP). The spectral data are analyzed with a chemometric model, producing a hyperspectral image (a chemogram) used to identify LRP in the interrogated region. In this paper, we describe a FT-IR microscopy system for measurement of the NIR scattering and absorption properties of healthy and diseased regions of human coronary arteries in small volumes (~10 μl). Scattering and absorption coefficients are obtained from sequential 140 um x 140 um regions of interest across the face of 500-micron thick, saline-irrigated fresh coronary artery sections. A customized FTIR microscope, measurement protocol, and inversion algorithm are used for optical property determination, and the system is calibrated using measurements of tissue-simulating phantoms having well-characterized optical properties. Tissue optical properties are co-registered with brightfield transmission images as well as with stained histologic thin sections (H&E, Movat Pentachrome, and Oil Red O) acquired from an immediately-adjacent section. The ultimate goal of these experiments is to establish a mechanistic link between the multivariate model predictions displayed on the InfraReDx chemogram and the light-tissue interactions that govern the measured NIR reflectance spectra.