Device and method for non-invasively evaluating a target of interest of a living subject
Inventors
Mahadevan-Jansen, Anita M. • Dickensheets, David • Lieber, Chad
Assignees
Montana State University Bozeman • US Department of Veterans Affairs • Vanderbilt University
Publication Number
US-8300220-B2
Publication Date
2012-10-30
Expiration Date
2030-02-25
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Abstract
A probe using integrated confocal reflectance imaging, confocal Raman spectroscopy, and gross spatial imaging for non-invasiveIy evaluating a target of interest of a living subject. In one embodiment, the probe includes a casing with first and second ends, and first, second and third optical pons The firsi and second optical ports are located at the first end of the casing and the third optical port is located at the second end of the casing such that the first and third optical ports define a first optical path therebetween and the second and third optical ports define a second optical path therebetween, respectively. Each optical path has first and second portions, where the second portions of the first and second optical paths arc substantially overlapped and proximal to the third optical port.
Core Innovation
The invention relates to a device and method for non-invasive evaluation of a target of interest in a living subject by integrating confocal reflectance imaging, confocal Raman spectroscopy, and gross spatial imaging within a single handheld probe. The probe comprises a casing with three optical ports arranged to define two optical paths that substantially overlap near the third optical port. This configuration allows simultaneous acquisition of morphological and biochemical information from the target.
The probe incorporates various optical components such as collimation and coupling lenses, mirrors, band pass and long pass filters, a scanning member, an electronic imaging device, and a focus control device arranged to facilitate the collection of excitation light and backscattered light, including elastically scattered and wavelength shifted Raman light. The design enables raster scanning of excitation light onto a target, collection and separation of elastic and Raman scattering, and real-time imaging of the target tissue.
The problem addressed by the invention is the limitation of conventional Raman spectroscopy techniques, which provide biochemical characterization but limited microstructural information and may have weak Raman signal strength for imaging. Additionally, there is a need for a non-invasive, objective, and accurate tool for differentiation of normal and cancerous skin tissues to improve diagnosis and management, which current methods do not adequately fulfill.
Claims Coverage
The patent includes several independent claims covering a handheld probe integrating multiple imaging and spectroscopic methods, methods of non-invasive evaluation and diagnosis, and the structural arrangement of the optical probe. The main inventive features of these claims relate to the design and function of the integrated probe, the method steps for evaluation, and the system configuration.
Integrated optical paths in a handheld probe
A probe comprising a casing with first, second, and third optical ports at opposite ends defining overlapping first and second optical paths. The optical paths include components such as a collimation lens, coupling lens, objective lens assembly, mirrors, band pass and long pass filters, scanning member, electronic imaging device, and focus control device arranged so that certain components are placed at distinct portions of the optical paths allowing integrated confocal reflectance imaging, confocal Raman spectroscopy, and gross spatial imaging.
Selective routing and detection of elastically scattered and Raman shifted light
Excitation light is delivered through the first optical port, collimated, filtered, and scanned onto the target. Backscattered light, including elastically scattered and wavelength shifted Raman light, is collected and de-scanned. Elastically scattered light is reflected along one path for morphological imaging, while Raman-shifted light is reflected along a separate path for biochemical analysis. This selective routing is accomplished using a combination of dichroic, hot mirrors, and scanning members.
Dynamic focus control and scanning
The objective lens assembly is engaged with a focusing mechanism for selective translation to control depth of focus on the target. A bi-axial MEMS mirror is used as a scanning member to raster scan the excitation light on the target enabling confocal imaging.
Multi-modal imaging integration in a handheld probe
The probe integrates confocal reflectance imaging providing morphology, confocal Raman spectroscopy providing biochemical content, and gross spatial imaging with real-time bright-field imaging within a handheld device. The design includes a CCD camera for visible light imaging, ring LED illumination, and a transparent window for target placement and illumination.
Method of non-invasive evaluation and diagnosis
A method employing the probe to capture gross spatial images, selectively capture confocal images of specific areas, then capture Raman spectra for smaller subareas, and compare these data to known signatures for diagnosis, including skin disease and skin cancer, all performed non-invasively with a handheld integrated probe.
The claims collectively cover an integrated handheld optical probe system and associated methods that provide combined confocal reflectance imaging, confocal Raman spectroscopy, and gross spatial imaging for non-invasive evaluation and diagnosis of living tissue, emphasizing structural and biochemical information acquired through a specialized optical design and scanning methodology.
Stated Advantages
Provides real-time, automated, non-intrusive spectral and spatial information about tissue biochemistry and structure.
Combines cellular morphology and chemical specificity to form a powerful multimodal diagnostic tool.
Handheld, compact design allowing for easy use in clinical settings such as physician or dermatologist offices.
Enables objective and definitive diagnosis and tracking of skin lesions potentially reducing unnecessary excisions.
Uses the same excitation source for both confocal Raman measurements and confocal reflectance imaging simplifying device design.
Documented Applications
Non-invasive differential diagnosis of skin lesions, including distinguishing normal, benign, and malignant skin tissue.
Non-invasive evaluation of biochemical compositions and morphological details of normal and cancerous skin lesions in living subjects.
Routine tracking and monitoring of skin lesions for early cancer detection in clinical and general physician settings.
Real-time clinical use for diagnosing skin cancer using integrated confocal reflectance imaging, confocal Raman spectroscopy, and gross spatial imaging.
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