Measurement of cerebral microvascular compliance in a model of atherosclerosis with optical coherence tomography.

Optical coherence tomography (OCT) has recently been used to produce 3D angiography of microvasculature and blood flow maps of large vessels in the rodent brain in-vivo. However, use of this optical method for the study of cerebrovascular disease has not been fully explored. Recent developments in neurodegenerative diseases has linked common cardiovascular risk factors to neurodegenerative risk factors hinting at a vascular hypothesis for the development of the latter. Tools for studying cerebral blood flow and the myogenic tone of cerebral vasculature have thus far been either highly invasive or required ex-vivo preparations therefore not preserving the delicate in-vivo conditions. We propose a novel technique for reconstructing the flow profile over a single cardiac cycle in order to evaluate flow pulsatility and vessel compliance. A vascular model is used to simulate changes in vascular compliance and interpret OCT results. Comparison between atherosclerotic and wild type mice show a trend towards increased compliance in the smaller arterioles of the brain (diameter < 80µm) in the disease model. These results are consistent with previously published ex-vivo work confirming the ability of OCT to investigate vascular dysfunction.

Co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system.

Spectrally encoded confocal microscopy and optical frequency domain imaging are two non-contact optical imaging technologies that provide images of tissue cellular and architectural morphology, which are both used for histopathological diagnosis. Although spectrally encoded confocal microscopy has better transverse resolution than optical frequency domain imaging, optical frequency domain imaging can penetrate deeper into tissues, which potentially enables the visualization of different morphologic features. We have developed a co-registered spectrally encoded confocal microscopy and optical frequency domain imaging system and have obtained preliminary images from human oesophageal biopsy samples to compare the capabilities of these imaging techniques for diagnosing oesophageal pathology.

Preliminary evaluation of noninvasive microscopic imaging techniques for the study of vocal fold development.

Understanding pediatric voice development and laryngeal pathology is predicated on a detailed knowledge of the microanatomy of the layered structure of the vocal fold. Our current knowledge of this microanatomy and its temporal evolution is limited by the lack of pediatric specimen availability. By providing the capability to image pediatric vocal folds in vivo, a noninvasive microscopy technique could greatly expand the existing database of pediatric laryngeal microanatomy and could furthermore make longitudinal studies possible. A variety of natural-contrast optical imaging technologies, including optical frequency domain imaging (OFDI), full-field optical coherence microscopy (FF-OCM), and spectrally encoded confocal microscopy (SECM) have been recently developed for noninvasive diagnosis in adult patients. In this paper, we demonstrate the potential of these three techniques for laryngeal investigation by obtaining images of excised porcine vocal fold samples. In our study, OFDI allowed visualization of the vocal fold architecture deep within the tissue, from the superficial mucosa to the vocalis muscle. The micron-level resolution of SECM allowed investigation of cells and extracellular matrix fibrils from the superficial mucosa to the intermediate layer of the lamina propria (LP) (350 microm penetration depth). The large field of view (up to 700 microm), penetration depth (up to 500 microm), and resolution (2x2x1microm [XxYxZ]) of FF-OCM enabled comprehensive three-dimensional evaluation of the layered structure of the LP. Our results suggest that these techniques provide important and complementary cellular and structural information, which may be useful for investigating pediatric vocal fold maturation in vivo.

Large area confocal microscopy.

Imaging large tissue areas with microscopic resolution in vivo may offer an alternative to random excisional biopsy. We present an approach for performing confocal imaging of large tissue surface areas using spectrally encoded confocal microscopy (SECM). We demonstrate a single-optical-fiber SECM apparatus, designed for imaging luminal organs, that is capable of imaging with a transverse resolution of 2.1 microm over a subsurface area of 16 cm2 in less than 1 min. Due to the unique probe configuration and scanning geometry, the speed and resolution of this new imaging technology are sufficient for comprehensively imaging large tissues areas at a microscopic scale in times that are appropriate for clinical use.

Rapid wavelength-swept spectrally encoded confocal microscopy.

Spectrally encoded confocal microscopy (SECM) is a technique that allows confocal microscopy to be performed through the confines of a narrow diameter optical fiber probe. We present a novel scheme for performing SECM in which a rapid wavelength swept source is used. The system allows large field of view images to be acquired at rates up to 30 frames/second. Images of resolution targets and tissue specimens acquired ex vivo demonstrate high lateral (1.4 mum) and axial (6 mum) resolution. Imaging of human skin was performed in vivo at depths of up to 350 mum, allowing cellular and sub-cellular details to be visualized in real time.

Extended-Cavity Semiconductor Wavelength-Swept Laser for Biomedical Imaging.

We demonstrate a compact high-power rapidly swept wavelength tunable laser source based on a semiconductor optical amplifier and an extended-cavity grating filter. The laser produces excellent output characteristics for biomedical imaging, exhibiting >4-mW average output power, <0.06-nm instantaneous linewidth, and >80-dB noise extinction with its center wavelength swept over 100 nm at 1310 nm at variable repetition rates up to 500 Hz.

High-speed wavelength-swept semiconductor laser with a polygon-scanner-based wavelength filter.

Ultrahigh-speed tuning of an extended-cavity semiconductor laser is demonstrated. The laser resonator comprises a unidirectional fiber-optic ring, a semiconductor optical amplifier as the gain medium, and a novel scanning filter based on a polygonal scanner. Variable tuning rates up to 1150 nm/ms (15.7-kHz repetition frequency) are demonstrated over a 70-nm wavelength span centered at 1.32 microm. This tuning rate is more than an order of magnitude faster than previously demonstrated and is facilitated in part by self-frequency shifting in the semiconductor optical amplifier. The instantaneous linewidth of the source is <0.1 nm for 9-mW cw output power and a low spontaneous-emission background of -80 dB.

Endovascular procedures under near-real-time magnetic resonance imaging guidance: an experimental feasibility study.

PURPOSE: The purpose of this study was to assess the feasibility of insertion of endovascular stents and the precision of an open-field interventional magnetic resonance imaging (iMRI) system in an in vivo model. METHODS: A feasibility study was undertaken at a university-affiliated hospital. Three male piglets with an average age of 6 months and a weight between 70 and 77 kg and two 3-month-old male piglets that weighed 40 to 44 kg were anesthetized. The five piglets underwent placement of nitinol stents inserted through the right femoral artery, under the guidance of a SIGNA-SP 0. 5T open-configuration iMRI unit. With a dedicated high-resolution near-real-time MRI sequence, the stent was guided and deployed onto a predefined target. RESULTS: The main outcome measures were the duration of the procedure from the beginning of positioning to the end of deployment of the stent, the final position of the stent in relation to the target on the iMRI screen, and comparison with autopsy findings. Three stents were deployed within the aorta at the level of the renal arteries, and two were deployed within the right iliac artery just below the aortic trifurcation. The average duration of the endovascular deployment was 13 minutes. There was an agreement of 0.6 mm in the position of the stent as observed on iMR images and found at autopsy. When the piglets were sacrificed, the average distance between the stents and the predefined target was 7. 8 mm, mostly because of the migration of one stent. Axial views allowed for accurate determination of stent impaction on the vascular wall. CONCLUSIONS: This study confirms the feasibility of stent deployment under near-real-time MRI guidance. It also emphasizes some inherent characteristics that hold promise with regard to other conventional techniques: stents and vascular structures are visualized in near-real-time in any desired plane, and the technique is performed without the potential adverse effects of ionizing radiations and iodinated contrast agents.

In vitro evaluation of the accuracy of open-configuration MRI in endovascular techniques.

The purpose of this study was to determine the accuracy of an interventional magnetic resonance imaging (iMRI) system to position an endovascular catheter in an in vitro model that simulated an infrarenal aortic aneurysm. Adequate visualization of abdominal aortic aneurysms (AAAs) was shown previously in humans. A dedicated near-real-time imaging protocol readily available on a Signa SP 0.5T open configuration MRI unit (General Electric Medical Systems, Milwaukee, WI, USA) was used to image the AAAs of ten human volunteers. A pulsatile in vitro model that simulated an AAA was built, which included the kidneys, the renal arteries, the aorta, and the iliac arteries. A catheter was advanced to a predetermined target through one of the iliac limbs of the model. Using two different techniques, the accuracy with which an interventionist could position the endovascular catheter under the near-real-time guidance of the iMRI system was evaluated. The AAAs of all ten patients were visualized, including the aneurysm wall, the thrombus within it, and the residual lumen, while maintaining adequate contrast, signal, and imaging speed. The position of the catheter was evaluated on target in 42 in vitro procedures. This series of tests showed an average accuracy of 1 mm for catheter positioning. The near-real-time imaging mode of the iMRI system enabled satisfactory evaluation of human AAAs, and it showed great accuracy for catheter positioning in the in vitro model. These results provide optimism regarding the potential of iMRI in endovascular surgery.