Coherence Gated Doppler Blood Flow Sensor

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Researchers at the University of Maryland have developed a low-cost fibre sensor for detecting blood flow. It has a diameter of just 125 microns, meaning it could be incorporated into a surgical instrument to alert the operator that they are approaching a blood vessel. It combines features of laser Doppler flowmetry and low coherence interferometry to provide a measurement with high spatial localisation, but without many of the complications of a full Doppler optical coherence tomography (OCT) system.

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Capsule OCT Endomicroscopy

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A team from Massachusetts General Hospital (MGH) has developed a tethered endomicroscopy capsule, offering a potential alternative to endoscopic tissue biopsy. It uses optical coherence tomography (OCT) to generate high-resolution cross-sections through the walls of the oesophagus. Capsules are already in use for video endoscopy, and OCT has been shown to have value in the diagnosis of Barrett’s oesophagus, but this is the first time the two technologies have been combined.
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Cross Sectional Dual Axis Endomicroscopy

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When biopsies are reviewed by pathologists in histology, they are typically viewed in ‘cross-section’ – a slice is cut perpendicular to the surface of the tissue. In contrast, microscopy performed directly on the patient (in vivo or endomicroscopy) usually generates en face images – slices in the plane of the tissue surface. Some endomicroscopes designs allow vertical cross-sections to be generated from stacks of en face images at varying depths, but this is nowhere near to being a real time approach. A group from the University of Michigan has now developed a handheld endomicroscope which can generate vertical cross-sections with a frame rate of 10 Hz.
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High Resolution Fluorescence Endomicroscopy Using a Multi-mode Fibre

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I recently discussed a paper by a group from Korea University,Seoul, who had developed a reflection-mode widefield endomicroscope using a multi-mode fibre. Other people have been thinking along the same lines, including a Swiss group who have recently published details of another multi-mode fibre based device. Unlike the widefield implementation, this method uses digital phase conjugation to scan a point of light at the far-end of the fibre, making fluorescence imaging possible. The basic idea isn’t new, but the group was able to demonstrate better resolution than previous reports through the use of a very high NA, double clad fibre.
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High Speed Multi-photon PLIM

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Phosphorescence lifetime imaging microscopy (PLIM) allows substances or tissues with different phosphorescence lifetimes to be identified with high spatial resolution. PLIM hasn’t found many practical applications so far, but it could be useful as a way of measuring oxygen concentration in tissues. Depth resolved images can be obtained using multi-photon excitation, a technique which ensures that all the signal comes from the focal plane. Unfortunately, relatively long phosphorescent lifetimes make the point-by-point scanning used in multi-photon microscopy very time consuming. Attempts to improve the frame rate using parallel excitation can result in cross-talk between pixels and blurring of the image. Now, a group from Cornell University has devised a way to acquire parallel excitation PLIM images which are free from cross-talk.

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Dual Mode Endomicroscopy for Assessing Gene Transfection

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Fibre bundle endomicroscopes usually operate in fluorescence mode: the tissue is stained with a fluorescent dye which, when illuminated at a certain wavelength, emits light at a longer wavelength. Collecting this fluorescent emission tends to produce clear, high contrast images, and also allows back-reflections from the fibre bundle to be removed using wavelength selective filters. Reflectance mode endomicroscopes, which create an image from the light back-scattered from the tissue, have been demonstrated several times, but have found little practical application. Now, Cha et al. from John Hopkins University have developed a dual-mode device that simultaneously collects both fluorescence and reflectance images. They have used this device to measure the efficacy of gene transfection – the deliberate insertion of genes into cancerous cells.
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Endomicroscopy Through a Multimode Fibre

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Most modern endoscopes use miniaturised cameras to capture macroscopic images, but this technology is not suitable for very high resolution endomicroscopy systems. The current generation of endomicroscopes either have a scanning head at the distal tip of the probe, or use a fibre bundle to relay the image out of the patient. The fibre bundle approach allows for the smallest diameter probes, but also has disadvantages, including a severe resolution/field of view trade-off. A recent paper in Physics Review Letters has suggested there might be another possibility. The authors managed to transmit an image through a single multimode optical fibre with a diameter of only 200 microns. They achieved a resolution of around 2 microns and a field of view equal to the fibre core diameter, opening up the prospect of an ultra-thin endomicroscope reaching parts of the body which are currently inaccessible.

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Mosaicing of Widefield Endomicroscopy Images

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The Bioengineering Department at Rice University in Texas has been developing fibre-bundle based widefield endomicroscopes for several years. While these devices lack the depth sectioning capabilities of confocal endomicroscopes, they can still produce useful images from certain tissues if a suitable topical fluorophore is applied. A recent paper from Richards-Kortum’s Group at Rice has demonstrated ‘real time’ mosaicing using their endomicroscope, allowing characterisation of much larger areas of tissue than would otherwise be possible.
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Combined Fluorescence and White Light Laparoscopy

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If we wanted to build a fluorescence imaging system for minimally invasive surgery then there are a few things we would need to consider. We would want it to be simple to implement, reasonably lightweight and, most importantly, compatible with existing laparoscopes. We’d also like to be able to obtain a conventional white light view at the same time as the fluorescence. Researchers at GE have developed a device which meets all of these requirements, and recently published the details in the open access journal Biomedical Optics Express. Their suggested application is to help identify nerves during surgery, but the technique could easily be used for a range of purposes.

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A Gentle Introduction to Endomicroscopy

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Many diseases, including cancer, can be diagnosed by extracting tissue samples from the patient’s body and studying them under a microscope. This is called histopathology. An alternative technique called endomicroscopy has recently been developed. It allows tissue to be imaged at the microscopic level without removing it from the patient. This post introduces the topic of endomicroscopy – sometimes known as ‘confocal laser endomicroscopey’ or CLE – to the non-specialist.
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