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International audience; Aim To optimize conventional coronary optical coherence tomography (OCT) images using the attenuation-compensated technique to improve identification of plaques and the external elastic lamina (EEL) contourMethods and results The attenuation-compensated technique was optimized via manipulating contrast exponent C, and compression exponent N, to achieve an optimal contrast and signal-to-noise ratio (SNR). This was applied to 60 human coronary lesions (38 native and 22 stented) ex vivo conventional coronary OCT images acquired from heart autopsies of 10 patients and matching histology was available as reference. Three independent reviewers assessed the conventional and attenuation-compensated OCT images blindly for plaque characteristics and EEL detection. Conventional OCT and compensated OCT assessment were compared against histology. Using an optimized algorithm, the attenuation-compensated OCT images had a 2-fold improvement in contrast between different tissues in both stented and non-stented epicardial coronaries (P < 0.05). Overall sensitivity and specificity for plaque classification increased from 84 to 89% and from 92 to 94%, respectively, with substantial agreement among the three reviewers (Fleiss' Kappa k, 0.72 and 0.71, respectively). Furthermore, operators were 2.5 times more likely to identify the EEL contour in the attenuation-compensated OCT images (k = 0.72) than in the conventional OCT images (k = 0.36)Conclusion The attenuation-compensated technique can be retrospectively applied to conventional OCT images and improves the detection of plaque characteristics and the EEL contour. This approach could complement conventional OCT imaging in the evaluation of plaque characteristics and quantify plaque burden in the clinical setting.

In vivo imaging technologies drive the development of improved cancer therapies by revealing critical aspects of the complex pathophysiology of solid tumors in small animal models[1]. The abnormal vascular function, which predicts tumor malignant potential and presents broad barriers to effective treatment, has been studied at the subcellular size scale using multiphoton (MP) microscopy [2], and at significantly larger size scales using ultrasound, μCT and μMRI[3-5]. However, limited in vivo imaging approaches exist to study the vascular function at the network level, i.e., with sufficient resolution to discern smaller vessels while maintaining a field of view and penetration depth large enough to reveal interconnectivity and inhomogeneities across the tumor and surrounding tissue. One promising technology operating at this size scale is optical frequency domain imaging (OFDI) using Doppler-methods to detect blood flow. We have recently designed and constructed a Doppler OFDI system specifically for the application of vascular imaging in tumor models[6]. The technical aspects of this system that enable the required levels of flow sensitivity and imaging speed are described. Beam scanning patterns used for this system will be reviewed and analyzed. The construction of the imaging system including high-rate data acquisition with the ability to continuously stream data at rates of 400 MB/sec will be described. Finally, the algorithms used to process, filter, and display the acquired volumetric datasets as vascular projections will be described. To validate the developed Doppler OFDI instrument for this application, its capabilities and limitations were explored relative to those of multiphoton microscopy, the standard optical imaging approach applied to the study of tumor biology. We investigated both the resolution and penetration depth, as well as differences in vascular visibility resulting from the differing mechanisms of contrast (endogenous flow in Doppler OFDI, exogenous fluorescent agent in multiphoton microscopy). Figure 1 illustrates a comparison between Doppler and MP in vivo imaging of a region of normal brain in a mouse cranial window model. Semi-automated vessel tracing algorithms were applied to each dataset, allowing quantitative comparison of visualized vessel sizes. As expected, multiphoton microscopy provides higher resolution, but, as indicated in Fig. 1(e), each modality provides consistent sizing of vessels exceeding 10 microns in diameter. To compare the ability of each modality to image the abnormal vessels within and surrounding tumors, we performed imaging with each modality in a series of tumors in a dorsal skin chamber models. ©2010 IEEE. 59 60 59-60

Intravital multiphoton microscopy has provided powerful mechanistic insights into health and disease and has become a common instrument in the modern biological laboratory. The requisite high numerical aperture and exogenous contrast agents that enable multiphoton microscopy, however, limit the ability to investigate substantial tissue volumes or to probe dynamic changes repeatedly over prolonged periods. Here we introduce optical frequency domain imaging (OFDI) as an intravital microscopy that circumvents the technical limitations of multiphoton microscopy and, as a result, provides unprecedented access to previously unexplored, crucial aspects of tissue biology. Using unique OFDI-based approaches and entirely intrinsic mechanisms of contrast, we present rapid and repeated measurements of tumor angiogenesis, lymphangiogenesis, tissue viability and both vascular and cellular responses to therapy, thereby demonstrating the potential of OFDI to facilitate the exploration of physiological and pathological processes and the evaluation of treatment strategies. © 2009 Nature America, Inc. All rights reserved. 15 1219 1223 1219-1223

Current medical imaging technologies allow visualization of tissue anatomy in the human body at resolutions ranging from 100 micrometers to 1 millimeter. These technologies are generally not sensitive enough to detect early-stage tissue abnormalities associated with diseases such as cancer and atherosclerosis, which require micrometer-scale resolution. Here, optical coherence tomography was adapted to allow high-speed visualization of tissue in a living animal with a catheter-endoscope 1 millimeter in diameter. This method, referred to as “optical biopsy,” was used to obtain cross-sectional images of the rabbit gastrointestinal and respiratory tracts at 10-micrometer resolution.

Optical coherence tomography (OCT) is an optical imaging technique that is capable of performing micron-scale, cross-sectional imaging of internal microstructure in biological systems. OCT is analogous to ultrasound B mode imaging except that it uses light rather than sound and performs imaging by measuring the back-scattered intensity of light from structures in tissue. We describe recent advances in OCT technology including the application of short pulse solid state lasers based on Ti: Al2O3 and Cr: Mg2SiO4 to enable high-resolution, high-speed imaging as well as the development of OCT catheter/endoscope delivery to permit imaging of internal organ systems. OCT enables the nonexcisional, in situ, real-time imaging of tissue microstructure and is thus a powerful and promising technique for optical biopsy.

A need exists in medicine for a technology capable of 'optical biopsy,' imaging at or near the resolution of histopathology without the need for excisional biopsy. Optical coherence tomography (OCT) is a recently developed imaging technology that uses infrared light to generate cross-sectional images on a micron scale. In this work, the feasibility of OCT for optical biopsy was confirmed with in vitro tissue from the skeletal and male reproductive systems. This work supports the hypothesis that OCT is an attractive technology for in vivo optical biopsy.

This study evaluated a novel method for modulation of neuronal excitability using non-invasive delivery of millimeter waves. Millimeter waves at 60 GHz and incident power density of 100-600 μW/cm^2 were applied to three intact segmental ganglia of the adult leach, and intracellular neuronal activity was recorded from the Retzius neurons using intracellular glass electrode. Transient dosedependent increase in the plasma membrane permeability was observed. In addition, in one of the examined neurons, a decrease in the neuronal firing rate was also evident. The results provide strong evidence for the feasibility of modulating neuronal excitability using non-invasive delivery of millimeter waves, and will be explored further for applications in basic neuroscience and treatment of neurological disorders.