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    • 专利摘要:
    EFFICIENT MODULATED IMAGE The present invention relates to a cloudy sample measurement apparatus comprising a plurality of light sources for illuminating a cloudy sample target area with non-spatial structured light, a projection system for illuminating the cloudy sample target area with spatial structured light, a sensor to collect light from the target area of cloudy sample, and a processor to analyze the data captured by the sensor to produce dispersion and absorption coefficients. One method comprises lighting the sample with structured spatial light, collecting reflected light from the sample in a series of wavelengths, lighting the sample with non-spatial structured light, collecting reflected light from the sample in a series of wavelengths, and combining the measurements of the collected light to obtain the optical properties of the sample and / or the concentration of absorption or fluorescent molecules. The wavelengths of the space and non-space light sources are preferably different.
    公开号:BR112015010459B1
    申请号:R112015010459-2
    申请日:2013-11-07
    公开日:2021-01-26
    发明作者:David Cuccia；Amaan Mazhar
    申请人:Modulated Imaging, Inc.；
    IPC主号:
    专利说明:

    TECHNICAL FIELD
    [001] The modalities described here generally refer to modulated imaging for quantitative characterization of tissue structure and functions. Specifically, the present invention relates to systems and methods that facilitate efficient modulated imaging. BACKGROUND OF THE INVENTION
    [002] The quantitative characterization of tissue structure and function is one of the most challenging problems in medical imaging. Optical diffusion methods can be used to measure biological tissues or other cloudy samples (ie, light scattering) with deep resolution and sensitivity from microns to centimeter-wide scales, limited by fundamental light-tissue interactions. Important tissue components (referred to as chromophores) such as oxyhemoglobin, deoxyhemoglobin and water can be detected optically and act in a correlated manner to assess various indicators or health status indices of local or psychological tissue. Examples of such indices include oxygen saturation in the tissue (stO2, or fraction of oxygenated blood), total blood volume (ctTHb), fraction of water in the tissue (ctH2O), and spraying or tissue metabolism. These indices can provide a powerful means for doctors to carry out diagnoses and / or guidance therapies. These chromophores can be detected because they have absorption spectra with aspects that can be detected, in the visible and / or near infrared regions. In essence, a light source can be used to illuminate a tissue sample, and the re-emitted light can be used to measure the absorption aspects in the tissue and the amount of chromophore of interest. This is practically a difficult measurement due to the presence of dispersion in the tissue. A class of probe-based technologies has been described in the academy and has also been commercially translated by a number of companies (Somanetics, Huchinson, ViOptix). Each of these technologies uses a series of different algorithms and hardware components (light sources, spectral detection) to abort the problem to calculate, correct or control tissue dispersion to obtain meaningful information on hemoglobin and tissue oxygenation. These probes benefit from the large selection of single point detectors that provide spectral flexibility and high sensitivity. However, contact probes are subject to some major limitations. By nature, contact probes are not imaging technologies and are therefore not ideal for assessing large areas of tissue. This is important because the health of the tissue varies spatially frequently, for example, in tissue wounds (burns, ulcers, tissue flaps, etc.), where the spatial contrast can be present both between normal tissue and the wound, as well such as within the wound itself (for example, the vicinity of the wound versus the center of the wound). With the contact probes, to synthesize a low resolution image, several contact probes can be placed in various places on the tissue, or the probe needs to be scanned across the surface. Typical wounds can vary from a few mm in size to many cm, presenting a challenge for probe technologies to design and / or adapt to this wide variation.
    [003] The camera-based optical spectral imaging methods have also been developed in academia and commercially. A multi-spectral imaging technology using visible light (HyperMed) was applied to measure oxygenation of tissue over a wide field of view (~ 10 cm x 10 cm) and was applied to monitor diabetic injuries. Multiple spectral imaging methods typically employ wavelengths that sample only the upper surface layers of tissue (<1mm deep). While the near infrared (650 - 1000 mm) penetrates much deeper, the chromophore contrast in the reflected or transmitted light signal is more challenging to isolate and quantify, due to the presence of a strong tissue dispersion coefficient (this is compared to absorption ). A technology that can overcome this limitation and evaluate the health of the fabric over a wide field of view in non-contact both in the superficial layers of layer (~ 100um in depth) as well as secondary surface layers (1 to 10 mm) is more valuable and therefore, it is desired.
    [004] A new optical imaging method called Modulated Imaging (IM) has recently been introduced, which enables quantitative analysis of disease progression and therapeutic response in a wide field of view and tissue depth without requiring direct contact. MI has been described in US Patent 6,958,815 B2, referred to herein as Bevilacqua et al, the description of which is incorporated herein by reference. This technique involves illuminating biological tissue or another cloudy medium (a sample that is both dispersed and absorbent) with a spatially modulated light pattern (or “structured light”) at one or more optical wavelengths and analyzing the reflected light back collected or disseminated as a result of the tissue. A preferred modality of MI is called Spatial Frequency Domain Imaging (SFDI), in which the spatial light pattern, or structure, is sinusoidal, which allows an algorithmically simple way to detect the structured light contrast of a small number (typically 3 to 15) per wavelength of structured light measurements. When combined with multiple spectral imaging, optical properties at two or more wavelengths can be used to quantitatively determine the two “in-vivo” (within an organism) concentrations of chromophores that are relevant to the health of the tissue, for example , oxyhemoglobin (ctO2Hb), deoxyhemoglobin (ctHHb) and water (ctH2O).
    [005] To perform spectroscopic measurements (depends on wavelength) of chromophores, the MI technique requires collection of spatially structured light sent from the tissue at various wavelengths. This has been done until today, repeating the technique described by Bevilacqua et al for each desired wavelength. Therefore, scale the total imaging periods directly with the number of measured wavelengths. This can be particularly challenging for some near-infrared wavelengths where light sources are less bright, yield is low, and detector quantity efficiencies are low due to CCD limitations. For low-yield wavelengths, long integration periods (10s to 100sms) are required to obtain adequate signal for noise ratio. The light intensity must be increased at these wavelengths to reduce the integration time. However, this is limited by “etendue” (light property in an optical system) or light yield, hardware limitations of structured light projection, including both the light source (eg, LEDs, lasers, white light bulb) ), optical retransmission system (for example, lenses, waveguides, (for example, mirrors), as well as pattern generation technology (for example, reflective digital mirror microprocessor arrangement or silicon liquid crystal, standardized transmissive material or arrangement LCD, or holographic element.) Increasing the “brute strength” intensity of weak or inefficient wavelength bands can have other effects including increased energy consumption, increased thermal voltage (which can lead to additional source inefficiency and instability) and increased cooling requirements. Longer imaging periods also create a practical problem in medical applications (or other sensitive movement) because it leads to artifacts in the final image due to small movements of the measurement sample (eg tissue) being studied. Therefore, it is desirable to provide an apparatus and method that improves the capability of modulated imaging methods while maintaining accuracy, but improving the efficiency of the system and reducing the imaging period.
    [006] As briefly described above, MI comprises lighting a sample with one or more intensity patterns spatially structured over a large area (many cm2) of a tissue sample (or another cloudy one) and collecting and analyzing the light received from resultant lap of the sample. An analysis of the amplitude and / or phase of the spatially structured light received back from the sample can be used as a function of the spatial frequency or periodicity, often referred to as the modulation transfer function (MTF) to determine the sample's optical property information. at any different wavelength. Examples of optical properties of tissue include light absorption, light diffusion (magnitude and / or angular dependence), and light fluorescence. The analysis of these light dependency data (based on model or empirically deduced) can be used to generate 2D or 3D maps of quantitative absorption (μa) and reduced diffusion optical properties (μs'). Evaluations towards the region (multiple pixels) can also be produced by averaging or otherwise accumulating multiple results of spatial or deduced optical property. Using spatial frequency or periodicity information at various wavelengths, MI can separate the effects of absorption (μa) and fluorescence (μa) of diffusion (μs), which can result from physically different contrast mechanisms.
    [007] The mapping of the absorption coefficient, (μa), in multiple wavelengths, by the MI, successively enables quantitative spectroscopy of tissue chromophores including, but not limited to oxyhemoglobin, deoxyhemoglobin and water (ctO2Hb, ctHHb and ctH2O) and deduced physiology parameters such as oxygen saturation in the tissue and blood volume (stO2 and ctTHb). The phase of spatial variation of the light collected from the tissue can also be measured simultaneously, and produces topographic surface information. This combination of measurements makes it possible to view the 3D tissue profile, as well as calibration data to accommodate curved surfaces in the analysis. A typical data flow is shown in Figure 1.
    [008] An issue present in the measurement and analysis of IM is the imaging period. Longer imaging periods increase sensitivity to movement and ambient lighting, which can result in artifacts in the two dimensional maps of the measured biological metrics - particularly in clinical applications. Hardware limitations are a key reason for long imaging periods. High energy light sources, such as light emitting diodes (LEDs), can improve the problem, but the measurement time remains a problem in the near infrared. This is due to the fact that the LED energy and the sensitivity of the camera can depend a lot on the wavelength and the LED energy is limited by the cooling requirements and size of the device.
    [009] Figure 2 illustrates a sample data set of a childhood burn, collected with a state-of-the-art modulated imaging device that displays motion artifacts. Figure 2 (b) illustrates reflectance data versus wavelength and spatial frequency. It should be noted that the artifact high spatial frequency strip pattern in the demodulated 970nm data (right, bottom). Here the term demodulated data means that the amplitude extracted from the light received from the normalized tissue for the amplitude of the light illumination at each spatial frequency. In other words, demodulated data is the function of transferring the modulation of the illuminated tissue. These artifacts are due to movement during the long periods of integration required for that wavelength. As Figures 2 (c) highlight, a 10x longer integration period (ie, 5s) is required to acquire the data set at 970 nm compared to other shorter wavelengths (ie, only 0.5s) . Using all wavelength information to produce chromophores or diffusion amplitude / slope measurements results in sinusoidal artifacts in the deduced data as illustrated in the average diffusion amplitude image in Figure 2 (d).
    [010] It has been illustrated that if the measurement of the wavelength 970nm and therefore the analysis of water concentration (ctH2O) is excluded ctO2Hb and ctHHb can still be precisely calculated assuming a fraction of water of typical tissue. Figure 2 (c) illustrates the resulting analysis when 970nm data is excluded that correctly identifies a region of high dispersion that correctly identifies in the upper left corner of the child's arm, indicated by the black arrow. The region corresponds to the most serious site of the injury and is useful for identifying. However, water sensitivity is highly desirable in many studies, so it is not desirable to exclude 970 nm data.
    [011] In general, therefore, it is desirable to have the flexibility to capture spectral contrast measurements of target chromophores at various wavelengths, while simultaneously having a minimal increase in complexity, if any, for the structured light requirements of the imaging technique. modulated core. Therefore, it is desirable to provide an apparatus and method for removing the effects of artifacts on wavelengths with poor performance / sensitivity to provide complete information on the concentrations and / or distributions of all relevant components including ctH2O, ctO2Hb, and ctHHb and others (for example, bilirubin, methemoglobin, lipids, exogenous agents). SUMMARY OF THE INVENTION
    [012] The modalities provided here are aimed at systems and methods that facilitate efficient modulated imaging for quantitative characterization of tissue structure and function. In one embodiment, a device for measuring a cloudy sample comprises a lighting device that has a plurality of light sources configured to illuminate a target area of a cloudy sample with light that has no spatial structure, a projection system configured for illuminate the white area of the cloudy sample with light that has a spatial structure, a sensor configured to collect light from the target area of the cloudy sample, and a processor configured to analyze the data captured by the sensor to produce dispersion and absorption coefficients of the cloudy sample. The light sources configured to illuminate the sample with light do not have a spatial structure are arranged on the perimeter of the lighting fixture. The projection system comprises a series of switchable light sources. The wavelengths of light sources without a spatial structure are preferably different from the wavelengths of the spatial structure that has light.
    [013] In another embodiment, a method for measuring a cloudy sample comprises illuminating the sample with light that has a spatial structure, collecting reflected light from the sample to obtain the light sent from the sample in a series of wavelengths, ^ j, illuminate the sample that does not have a spatial structure, collect the reflected light from the sample to obtain the light sent from the sample in a series of wavelengths, ^ k, and combine the measurements obtained from the light that has a spatial structure and light without a spatial structure to obtain adjustment parameters, including the optical properties of the sample at wavelengths, and / or the absorption concentration or fluorescent molecules.
    [014] The wavelengths, ^ k, of the light that does not have a spatial structure is preferably different from the wavelengths of light that has a spatial structure, ^ j, i.e. ^ k * ^ j.
    [015] The combination of measurements obtained is performed using a scatter function that describes the dependence of dispersion on wavelengths to interpolate or extrapolate measurements at different wavelengths, ^ j obtained using light that has a spatial structure, to obtain evaluations for dispersion in ^ k wavelengths obtained using light that has no spatial structure.
    [016] The wavelength dispersion function is an energy regulation function described as μs' (A) = Ai * À -bi + A2 * À -b2 + ... + An * À -bn.
    [017] The systems, methods and aspects and advantages of the invention will be or will become clear to the person skilled in the art by examining the figures and detailed description that follow. All methods, aspects and advantages that are included within this description are intended to be within the scope of the invention, and to be protected by the appended claims. It is also intended that the invention is not limited to requiring details of the exemplary modalities. DESCRIPTION OF THE DRAWINGS
    [018] The attached drawings, which are included as part of this report, illustrate the preferred modality at the moment and, together with the general description provided above and the detailed description of the preferred modality provided below, serve to explain and teach the principles of present invention.
    [019] Figure i illustrates a flowchart of data processing of modulated imaging (IM) and typical MI data products. a) illustrates modulated intensity patterns projected onto the surface, b) illustrates demodulated amplitude and calibrated patterns at each frequency (three phase images per frequency), c) illustrates the standard fit for a multi-frequency model to determine properties, d) illustrates that phase demodulation provides separately information at the height of the tissue, which can be used for both curvature calibration and visualization. The data is processed for each pixel, generating spatial maps of optical properties, e) illustrates typical MI data products for a rat pedicle flap, with the distal end demonstrating the MI sensitivity for decreased spray (stO2), blood accumulation ( ctHHb & ctTHb), edema (ctH2o), and degradation of matrix / necrosis ultrastructure (μs').
    [020] Figure 2 are images that illustrate that long periods of measurement in a pediatric burned patient cause visible artifacts in the unworked and recovered MI data. (a) it is a photograph of a burnt tissue being studied; (b) are unworked data images that illustrate demodulated diffuse reflectance data at spatial frequency = 0.1 mm-1 (bottom) and spatial frequency = 0 mm-1 (top), for 4 wavelengths, from the left to the right 658 nm, 730 nm, 850 nm and 970 nm; (d) it is an image that illustrates oxygenation data of recovered tissue (StO2), from an analysis that includes 970 nm data, containing data artifacts; (e) is an image that illustrates oxygenation data (StO2) of recovered tissue, from an analysis that excludes demodulated 970 nm data. A black arrow indicates an increased oxygenation spatial area in the burned region, as compared to the surrounding tissue. This result is obscured in (d) the motion artifacts associated with the 970nm measurement.
    [021] Figure 3 illustrates a modality of a device with increased efficiency for modulated imaging, (a) illustrates a light rim for planar external light illumination, a projection system for structured light illumination, and an off-center camera , (b) illustrates a light and camera rim pattern that illustrates a rectangular structured light field in the center, overlaid by planar light illumination both of which are detected by the camera.
    [022] Figure 4 illustrates a planar light source with 9 positions to be populated by a different LED wavelength.
    [023] Figure 5 illustrates a planar illumination light ring with removable LED modules.
    [024] Figure 6 is a workflow diagram of an efficient MI analysis using structured and unstructured light.
    [025] Figure 7 illustrates example data illustrating a comparison between dispersion and absorption coefficients obtained from the modulated imaging apparatus described in the prior art and the present efficient modulated imaging apparatus and method. (a) is an image of a ‘Port Wine Spot (PWS)’ formed with a state of the art device. It should be noted that the PWS region on the check has a higher stO2 concentration compared to the adjacent areas due to increased vascularity. (b) is a graph of the dispersion coefficient as a function of wavelength comparing the state of the art (complete adjustment line) and efficient apparatus and method of the present invention (reduced data lines). (c) is a graph of the absorption coefficient as a function of the wavelength comparing the state of the art (complete adjustment line) and efficient apparatus and method of the present invention (reduced data lines).
    [026] Figure 8 illustrates graphs illustrating a comparison of extracted dispersion and absorption data from a Port Wine Spot (a) using the efficient modulated imaging device (y-axis) versus the use of the imaging device. state of the art (geometric axis x).
    [027] Figure 9a is a schematic illustrating an apparatus with light sources configured to illuminate the sample with light that does not contain a spatial structure and light containing a spatial structure.
    [028] Figure 9b is a schematic illustrating the apparatus of Figure 9a with a lighting condition using light that contains a spatial structure.
    [029] Figure 9c is a schematic illustrating the apparatus in Figure 9a with a lighting condition using light that has no spatial structure.
    [030] Figure 10 is a photograph of a modulation imaging instrument with structured and unstructured light sources, and a camera outside the geometric axis.
    [031] Figure 11 is a graph that illustrates an example of the relative efficiency of typical LEDs.
    [032] Figure 12 shows graphs that illustrate a comparison (top) of Complete and Efficient methods for recovering optical absorption properties, (bottom) a comparison, in percentage deviation from full analysis of the “other standard”, generally shows less than 1% difference in accuracy between approaches, thereby validating the Efficient method.
    [033] It should be noted that the figures are not necessarily drawn to scale and that elements of similar structures or functions are generally represented by similar numerical reference for illustrative purposes by all figures. It should also be noted that the figures are only intended to facilitate the description of the various modalities described here. The figures do not necessarily describe all aspects of the teachings described herein and do not limit the scope of the claims. DESCRIPTION
    [034] The modalities provided here are aimed at systems and methods that facilitate efficient modulated imaging for quantitative characterization of tissue structure and function. In conventional systems, the same pattern (or patterns) of spatially structured light was (were) illuminated at all relevant wavelengths. In one embodiment, a device for an efficient modulated imaging system separates light sources into spatially structured lighting and non-spatially modulated (planar) lighting. Here planar light is defined as light with substantially no pattern or structure of spatial intensity and structured light is defined as light illumination with pattern or structure of spatial intensity. The wavelengths of the planar and structured light illuminations are chosen to optimize the sensitivity as described below. Systems and methods for efficient modulated imaging are described in U.S. Provisional Patent Applications No. 61 / 793,331 and 61 / 723,721, whose applications are hereby incorporated by reference.
    [035] Figure 3 (a) illustrates a preferred embodiment of an efficient modulated imaging apparatus 10. Apparatus 10 comprises a lighting source 12 that has a series of unstructured external (planar) light sources 14 in its perimeter and configured to illuminate an area of a tissue sample, a projection system 15 that provides standardized (structured) light to illuminate the tissue sample area, and a detector or camera 18 positioned off center from both projection systems 16 and the external planar light source 12 and configured to collect light from the tissue sample area illuminated by the projection system 16 and the external planar light source 12. The planar light source 12, the projection system and the camera 18 they are coupled to a printed circuit board (PCB) 22, which includes a processor, power, controllers, memory and software that can be run on the processor and stored in memory. The light data collected by the camera 18 can be processed using the stored software and processor or sent to a computer or other processor for processing. The projection system 16, the camera 18 and the PCB 22 are mounted on an imaging base 20 that has a heat sink 21. Two position filters are coupled to the camera 18 and the projection system 16.
    [036] The external planar light source 12 is illustrated in Figure 3 (a) as a ring light assembly, but it can be other externally mounted light sources, including LEDs or lasers, that provide non-spatially structured lighting that does not cross the projection system 16. The ring light assembly includes a plurality of planar light sources 14 positioned around the periphery of a rim base 13. The base 13, together with a cover 11, is mounted outside a cover 15 of the modulated imaging device 10.
    [037] The selection of wavelengths is flexible both in the projection system 16 and in the unstructured planar (s) source (s) 12, 14. The projection system 16, which may include a projector DLP, a LOCOS projector, and the like, can comprise a series of switchable light sources such as Light Emitting Diodes (LEDs) of various wavelengths, such as, for example, LEDs 17 and 17 'illustrated in Figure 4 with respect to the planar light source 12, and is capable of providing modulated light versus various spatial frequencies or other structured light patterns. The light sources 14 in the external planar illuminator 12 can also be LEDs with one or more wavelengths, but specifically provide uniform illumination without a spatial structure. Structured projection 16 and external planar light sources 12 are generally directed to the same area in the tissue sample. Camera 18 is off-center of both planar light beam axes and structured light beam paths and collects light generally from the same area in the tissue sample that has been illuminated. A major benefit of the configuration of the external planar light source 12 is the increased transfer of unstructured light to the sample due to relaxed "no imaging" restrictions that do not require the light to be standardized and optically retransmitted to the samples. This configuration improves the efficiency of the system, reduces the imaging periods to obtain a desired signal-to-noise ratio (SNR), and increases the feasibility for applications when the measurement periods are limited by practical considerations such as usability and portability.
    [038] In a preferred embodiment, camera 18 is placed behind the outside axis of the external planar source 12, allowing minimal crosstalk from the light diffused directly from source 12 to camera 18. In a preferred embodiment, camera 18 is a CCD camera 12-bit monochrome, but can include any commercial CMOD camera.
    [039] In figure 3 (b) an example shows a configuration where the light, for example, formed by image through a source collection oriented in a ring. Other modalities are possible, but they all have the aspect that structured light and planar light sources 16 and 12 are usually illuminated in the same area in the tissue sample and that camera 18 is configured to form an image generally of the same area illuminated by structured and planar light sources 16 e12.
    [040] In another modality, as illustrated in Figure 4, each light source 14 in the planar source 12 has 9 positions that can be populated with any wavelength, which allows the flexible extension of the modulated imaging analysis to biological metrics that are sensitive to other wavelengths, see, for example, a multi-corresponding LED module 17 and a one-color LED module 17 ', which can be complementary to the wavelengths used to perform modulated core imaging (structured light) . Although illustrated as 9 positions, each light source 14 in the planar light source 12 can have 9 positions, 12 positions, etc.
    [041] In another embodiment, as shown in Figure 5, the base 13 of the external planar illuminator 12 provides supports 24 on which external light sources 14, such as LED modules 17, can be plugged in or taken out to allow a selection of reconfigurable wavelength.
    [042] In another embodiment, as shown in Figure 4, each light source 14, for example, an LED module 17 incorporates a homogenizer 26, such as an integration rod or diffuser, to disperse and spatially combine the production of multiple chips LEDs that can be individually addressed from the same source.
    [043] Operation and Analysis Method. Apparatus 10 for modulated imaging is operated as follows. Modulated imaging typically collects data over a series of distinct wavelengths li, 12, ..., 1n. each of which has a different performance or signal-to-noise ratio (SNR) in the camera or detector. The efficient apparatus 10 provided here separates these n wavelengths into two categories: 1) spatially structured wavelengths, l1S, lS2,., LSj and unstructured planar wavelengths l1P, l2P,., LkP. As described above, motion artifacts tend to appear for wavelengths for which the throughput or signal-to-noise ratio (SNR) is low. Low SNR can result from low source energy, weak projector - source coupling, reduced projector throughput, low received signal or low detector sensitivity for that wavelength. A low SNR wavelength requires correspondingly higher integration (ie camera exposure time), making it susceptible to movement. In an example of demonstrating the method provided in the context, spatially structured lighting was performed with high SNR wavelengths and unstructured planar lighting was performed with low SNR wavelengths. The efficient apparatus 10 provided here treats spatially structured and unstructured light differently in the analysis illustrated in Figure 6 and described in the following steps as illustrated in Figures 9b and 9c. As shown schematically in Figure 9a, the efficient apparatus 10 is illustrated to include a planar light source 12, a structured light source 16 and a camera 18 positioned above a cloudy sample or fabric 30. 1) As shown in Figure 9b, the structured light sources 16 are linked and scanned in the tissue sample 30 at one or more number of high SNR wavelengths (for example, tf = tf, tf, tf) as briefly described in US Patent 695815. The structured light illuminates the sample 30 in these wavelengths with a series of spatial frequencies, and the reflected and diffused light from the sample 30 is collected by the camera 18. These data can then be analyzed to obtain the transfer function of modulation and / or information optical property of the sample, for example, spatially resolved absorption and reduced dispersion (μa (tf) and μs' (tf)), using any physical model for light dispersion in biological tissue, or empirical research data based on a catalog of measurements or simulations. Examples of physical models that are considered for turbidity sampling are the Standard Diffusion Equation and Radiative Transport models for light transport. 2) Then, measurements on spatially structured wavelengths Â, j can be interpolated or extrapolated to unstructured wavelengths, ÂkP, based on the wavelength aspects dependent on optical properties in the sample of interest. For example, in the near infrared region, the dispersion coefficient deduced μs' (tf) can be adjusted for a wavelength energy regulation function such as μs' (A) = A * À - b, or generally μs' (A) = Ai * À -bi + A2 * À -b2 + ... + An * À -bn, interpolated or extrapolated at each pixel in the image detected by camera 18 to provide an estimated value for the dispersion coefficient for the unstructured wavelengths, μs' (Ap). For the equations shown, parameters A and b are free, non-negative variables, and n is at least 1. It must be observed by the deduction property such as the dispersion coefficient for an unstructured wavelength (ie, low SNR) of the data of structured wavelength (high SNR), the imaging time can be reduced by eliminating the need to acquire structured light images to directly measure μs' (Xp). This allows the use of a single unstructured light pattern to determine the remaining parameter, μa, (Z), thereby reducing the overall acquisition time and avoiding motion artifacts. 3) As shown in Figure 9c, structured light sources 16, which are at high SNR wavelengths, are then turned off, and planar light sources 12, which are low SNR wavelengths, are then turned on and used to illuminate the sample 30. The reflected light from the sample 30 is detected by the camera system 18, providing light sent at the desired wavelengths, such as diffusion reflectance coefficients, Rd Z. As the illustrative example, diffuse reflectance is measured in 970 nm to determine ctH2O sensitivity. It should be noted that this Step can alternatively be performed before Step 1, or interspersed with measurements within Step 1. 4) In the last step of analyzing the optical properties at the SNR, Z wavelengths are calculated using the combination of source measurements of structured planar and extrapolated or interpolated light. For example, the diffusion reflectivity values (Rd (Xp)) and the dispersion coefficients μs' (A) = A * À - b) evaluated in Ap; i.e. μs' (Ap) = A * (Xp) - b) can be combined with 1 parameter setting or lookup table calculation using a physical dispersion / reflection model for biological tissue, thereby producing μa (Ap). 5) At this stage the coefficients of the optical property (for example, dispersion and absorption) are fully determined for all wavelengths - measured directly from the modulation transfer function for data derived from the structured illumination wavelengths (ie, SNR high) and light data derived from the wavelengths of unstructured flat lighting (ie low SNR). 6) Chromophore concentrations and physiology indices can now be deduced from the dispersion coefficients totally dependent on wavelength and absorption.
    [044] It should be noted that Steps 2, 4 and / or 6 can be performed at any stage after the measurement of the underlying data. In addition, instead of being performed sequentially, Steps 2, 4 and / or 6 can be performed together in a direct “global” adjustment, or simultaneous analysis of all data entered to provide the desired yield, in order to obtain the concentration of absorption or fluorescent molecules.
    [045] Figure 7 illustrates an example comparison between 1) an analysis of total modulated imaging as obtained by the system prescribed by the state of the art (complete adjustment lines), and 2) the efficient device present and the method with a reduced number of lengths waveform (reduced data lines). There is excellent compliance between the two devices and methods. However, it should be noted that the advantage of the efficient device present is the removal of motion artifacts while providing good fidelity in the coefficients of the optical property (for example, dispersion and absorption) at all wavelengths.
    [046] To access the scope of measurements and patient populations that can be treated with this refined method, 10 red wine paint and 10 measurements from burned patients were collected and analyzed with a device and state of the art method as well as the device of efficient modulated imaging 10 and the method presented here. Figure 8 shows dispersion maps (Figure 8a) of absorption coefficients (Figure b) for various wavelengths obtained by the efficient device present (geometric axis y) versus those obtained from the state of the art device (geometric axis x). These data are diverse in terms of absorption coefficients: blood accumulation in PWS cases and bleaching / loss of epidermal melanin tissue in burn cases exhibit high and low absorption, respectively. However, Figure 8 illustrates correspondence one to one of the two indicated by a straight line with slope = 1.
    [047] In the present description the term camera refers to an optical detection system that creates an image in an area of a tissue sample in an array of pixel detectors, where the sample area formed with an image is much larger than the less spatial aspect to structured light illumination. In another modality, the reflected light from the sample is collected by a single detector, so that the light is collected from an area of the sample that is smaller than the smallest spatial aspect of the structured light that illuminates it from the projection system.
    [048] Recently, a modality of the MI system implemented with both LED flux illumination (unstructured) in front of the instrument, as well as standard MI-based structured projection based on a Digital Mirror Microprocessor Device.
    [049] Figure 10 illustrates a modality of an MI 10 device with structured light sources 116 unstructured 112. A camera 118 is configured to view both structured and unstructured light that reflects off a target positioned approximately one foot ( 30.48 cm) (1 ') on the front of the instrument.
    [050] Figure 11 illustrates an example of a relative efficiency of typical LEDs. Weak wavelengths (low peak values) result in poor imaging speed when required to emit through the projector. There are great candidates for flow lighting (unstructured) avoiding the need to use a low light yield projector (low “etendue”).
    [051] Figure 12 (top) illustrates a comparison of Complete and Efficient methods for recovering optical absorption properties. A standardized spectrum measurement that simulates tissue with low optical properties was used as an imaging target. For the total analysis, standard measurements of the spatial frequency domain were performed. For the Efficient analysis, a subsequent set of Total analysis was performed for 3 wavelengths (620, 690, 810 nm), and then the optical dispersion values were extrapolated or interpolated to other desired wavelengths (660, 730, 850 , 970 nm) to obtain the absorption coefficient only with unstructured (planar) data. This was repeated “backwards” with structured (660, 730, 850nm) and unstructured (620, 690, 810nm) wavelengths. Bottom: A comparison, in the present deviation from the total “gold standard” analysis, generally shows less than 1% difference in accuracy between approaches, thereby validating the Efficient method.
    [052] Although the invention is susceptible to several modifications, and alternative forms, specific examples of it have been shown in the drawings and are described in detail here. It should be understood, however, that the invention is not limited to the specific forms or methods described herein, on the contrary, the invention must cover all modifications, equivalences and alternatives that affect the spirit and scope of the appended claims.
    [053] In the above description, for the purpose of explanation only, the specific nomenclature is demonstrated to provide a complete understanding of the present description. However, it should be clear to one skilled in the art that these specific details are not required to practice the teachings of the present description.
    [054] The various aspects of representative examples and dependent claims can be combined in ways that are not specifically and explicitly listed in order to provide additional useful modalities of the present teachings. It should also be expressly noted that all variations in values of groups of entities describe each possible intermediate value or intermediate entity entirely for the purpose of the original description, as well as for the purpose of restricting the claimed matter.
    [055] It should be understood that the modalities described here are for the purpose of clarification and should not be considered as limiting the scope of the description. Various modifications, uses, substitutions, combinations, improvements, production methods without departing from the scope and spirit of the present invention must be clear to the person skilled in the art. For example, the reader should understand that the specific ordering and combination of the process actions described here are merely illustrative, unless stated otherwise, and the invention can be accomplished using different or additional process actions, or a combination or ordering of different process actions. As another example, each aspect of a modality can be mixed and combined with other aspects illustrated in other modalities. Aspects and processes known to those skilled in the art can similarly be incorporated as desired. Additional or obviously, aspects can be added or subtracted as desired. Therefore, the invention should not be restricted except in light of the appended claims and their equivalents.
    权利要求:
    Claims (7)
    [0001]
    1. Method for measuring a cloudy sample, CHARACTERIZED by the fact that it comprises the steps of: illuminating with a first light source a target area of the cloudy sample with only light spatially structured in a plurality of wavelengths and over a first optical projection path, collect reflected light from the cloudy sample to obtain spatially structured light sent from the sample in a first plurality of wavelengths, 2 j, illuminate with a second light source the target area of the blurred sample with only planar structured light in a plurality of wavelengths and along a second optical projection path, in which the first optical projection path differs from the second optical projection path, collecting reflected light from the cloudy sample to obtain planar structured light sent from the sample in one second plurality of wavelengths, 2k, and combine the measurements of the spatially structured light sent and the planar light sent collection of the cloudy sample to obtain adjustment parameters, where the adjustment parameters include one or more optical properties of the cloudy sample in the first and second pluralities of wavelengths 2j and 2k, and a concentration of absorption or fluorescent molecules.
    [0002]
    2. Method according to claim 1, CHARACTERIZED by the fact that each wavelength of the first plurality of wavelengths 2j has a different signal-to-noise ratio (SNR) and, in which each wavelength of the second plurality of 2k wavelengths, it has a different signal-to-noise ratio (SNR).
    [0003]
    3. Method according to claim 2, CHARACTERIZED by the fact that the first plurality of wavelengths 2j differs from the second plurality of wavelengths 2k.
    [0004]
    4. Method, according to claim 3, CHARACTERIZED by the fact that it additionally comprises, before illuminating the target area of the cloudy sample with only non-spatially structured light, extrapolating the measurements of the light sent having a spatial structure to calculate a dispersion coefficient for the second plurality of wavelengths, μ '(2PP).
    [0005]
    5. Method, according to claim 4, CHARACTERIZED by the fact that the measurements of non-spatially structured light are in diffuse reflectance coefficients, RdλP.
    [0006]
    6. Method, according to claim 5, CHARACTERIZED by the fact that μ '(λλk) and Rd λP are combined to produce μa (λpk).
    [0007]
    7. Method, according to claim 6, CHARACTERIZED by the fact that the signal-to-noise ratio (SNR) of the first plurality of wavelengths λj are greater in relation to the signal-to-noise ratio (SNR) of the second plurality of wavelengths λ k
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    同族专利:
    公开号 | 公开日
    BR112015010459A2|2017-07-11|
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    EP2898326B1|2018-03-14|
    AU2013341165A1|2015-05-14|
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    IL238599D0|2015-06-30|
    KR20150087258A|2015-07-29|
    US9883803B2|2018-02-06|
    EP3401678B1|2020-04-08|
    JP6321668B2|2018-05-09|
    MX2015005816A|2016-02-25|
    CN105190308B|2021-05-28|
    CA2889489C|2021-05-11|
    JP2018136331A|2018-08-30|
    US20150141839A1|2015-05-21|
    EP2898326A1|2015-07-29|
    JP2015533429A|2015-11-24|
    EP3401678A1|2018-11-14|
    AU2019257473B2|2021-06-24|
    WO2014074720A1|2014-05-15|
    CA2889489A1|2014-05-15|
    AU2013341165B2|2019-08-01|
    US8892192B2|2014-11-18|
    KR102251749B1|2021-05-13|
    IL238599A|2016-02-29|
    CN105190308A|2015-12-23|
    US20140128744A1|2014-05-08|
    EP2898326A4|2016-06-08|
    ES2787384T3|2020-10-16|
    JP6639549B2|2020-02-05|
    US10342432B2|2019-07-09|
    AU2019257473A1|2019-11-21|
    US20180228372A1|2018-08-16|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    US4286602A|1979-06-20|1981-09-01|Robert Guy|Transillumination diagnostic system|
    US4515165A|1980-02-04|1985-05-07|Energy Conversion Devices, Inc.|Apparatus and method for detecting tumors|
    US4407290B1|1981-04-01|1986-10-14|
    US4600011A|1982-11-03|1986-07-15|The University Court Of The University Of Aberdeen|Tele-diaphanography apparatus|
    JP3154997B2|1988-06-08|2001-04-09|エル． バーバー，ランダル|System for imaging random media|
    CN1230118C|1995-01-03|2005-12-07|无创伤诊断技术公司|Optical coupler for internal examination of biological tissue|
    US6618614B1|1995-01-03|2003-09-09|Non-Invasive Technology, Inc.|Optical examination device, system and method|
    JPH06103257B2|1988-12-19|1994-12-14|大塚電子株式会社|Method and apparatus for measuring absorption coefficient of substance using light scattering|
    US5353799A|1991-01-22|1994-10-11|Non Invasive Technology, Inc.|Examination of subjects using photon migration with high directionality techniques|
    US5369496A|1989-11-13|1994-11-29|Research Foundation Of City College Of New York|Noninvasive method and apparatus for characterizing biological materials|
    US5142372A|1990-03-08|1992-08-25|Alfano Robert R|Three-dimensional optical imaging of semi-transparent and opaque objects using ultrashort light pulses, a streak camera and a coherent fiber bundle|
    US5140463A|1990-03-08|1992-08-18|Yoo Kwong M|Method and apparatus for improving the signal to noise ratio of an image formed of an object hidden in or behind a semi-opaque random media|
    US5203339A|1991-06-28|1993-04-20|The Government Of The United States Of America As Represented By The Secretary Of The Department Health And Human Services|Method and apparatus for imaging a physical parameter in turbid media using diffuse waves|
    US5227912A|1991-10-30|1993-07-13|Ho Ping Pei|Multiple-stage optical kerr gate system|
    US5277181A|1991-12-12|1994-01-11|Vivascan Corporation|Noninvasive measurement of hematocrit and hemoglobin content by differential optical analysis|
    JP3142079B2|1992-03-19|2001-03-07|株式会社日立製作所|Optical CT device|
    US5299035A|1992-03-25|1994-03-29|University Of Michigan|Holographic imaging through scattering media|
    US5275168A|1992-03-31|1994-01-04|The United States Of America As Represented By The Secretary Of The Navy|Time-gated imaging through dense-scattering materials using stimulated Raman amplification|
    US5371368A|1992-07-23|1994-12-06|Alfano; Robert R.|Ultrafast optical imaging of objects in a scattering medium|
    US5418797A|1993-01-15|1995-05-23|The United States Of America As Represented By The Secretary Of The Navy|Time gated imaging through scattering material using polarization and stimulated raman amplification|
    US5416582A|1993-02-11|1995-05-16|The United States Of America As Represented By The Department Of Health And Human Services|Method and apparatus for localization and spectroscopy of objects using optical frequency modulation of diffusion waves|
    US6542772B1|1994-12-02|2003-04-01|Non-Invasive Technology, Inc.|Examination and imaging of biological tissue|
    JP3433508B2|1993-12-01|2003-08-04|浜松ホトニクス株式会社|Scattering absorber measurement method and scattering absorber measuring device|
    US5969822A|1994-09-28|1999-10-19|Applied Research Associates Nz Ltd.|Arbitrary-geometry laser surface scanner|
    JP3433534B2|1994-11-07|2003-08-04|浜松ホトニクス株式会社|Method and apparatus for measuring scattering and absorption characteristics in scattering medium|
    US5625458A|1994-11-10|1997-04-29|Research Foundation Of City College Of New York|Method and system for imaging objects in turbid media using diffusive fermat photons|
    US5931789A|1996-03-18|1999-08-03|The Research Foundation City College Of New York|Time-resolved diffusion tomographic 2D and 3D imaging in highly scattering turbid media|
    US6108576A|1996-03-18|2000-08-22|The Research Foundation Of City College Of New York|Time-resolved diffusion tomographic 2D and 3D imaging in highly scattering turbid media|
    US5919140A|1995-02-21|1999-07-06|Massachusetts Institute Of Technology|Optical imaging using time gated scattered light|
    WO1996029000A1|1995-03-23|1996-09-26|Philips Electronics N.V.|Device for carrying out optical measurements in turbid media|
    US6032070A|1995-06-07|2000-02-29|University Of Arkansas|Method and apparatus for detecting electro-magnetic reflection from biological tissue|
    MX9801351A|1995-08-24|1998-07-31|Purdue Research Foundation|Fluorescence lifetime-based imaging and spectroscopy in tissues and other random media.|
    US6405069B1|1996-01-31|2002-06-11|Board Of Regents, The University Of Texas System|Time-resolved optoacoustic method and system for noninvasive monitoring of glucose|
    US5928137A|1996-05-03|1999-07-27|Green; Philip S.|System and method for endoscopic imaging and endosurgery|
    US6076010A|1996-06-20|2000-06-13|Trustees Of The University Of Pennsylvania|Imaging spatially varying dynamic media with diffusing correlation waves|
    JP3660761B2|1996-10-03|2005-06-15|技術研究組合医療福祉機器研究所|Method and apparatus for measuring absorption information of scatterers|
    EP0897282A2|1996-12-03|1999-02-24|Koninklijke Philips Electronics N.V.|Method and apparatus for imaging an interior of a turbid medium|
    US6122042A|1997-02-07|2000-09-19|Wunderman; Irwin|Devices and methods for optically identifying characteristics of material objects|
    US5762607A|1997-03-19|1998-06-09|Schotland; John Carl|Emission tomography system and method using direct reconstruction of scattered radiation|
    US6208886B1|1997-04-04|2001-03-27|The Research Foundation Of City College Of New York|Non-linear optical tomography of turbid media|
    US6208415B1|1997-06-12|2001-03-27|The Regents Of The University Of California|Birefringence imaging in biological tissue using polarization sensitive optical coherent tomography|
    US6091984A|1997-10-10|2000-07-18|Massachusetts Institute Of Technology|Measuring tissue morphology|
    US6081322A|1997-10-16|2000-06-27|Research Foundation Of State Of New York|NIR clinical opti-scan system|
    US6240312B1|1997-10-23|2001-05-29|Robert R. Alfano|Remote-controllable, micro-scale device for use in in vivo medical diagnosis and/or treatment|
    US6937885B1|1997-10-30|2005-08-30|Hypermed, Inc.|Multispectral/hyperspectral medical instrument|
    GB9724835D0|1997-11-25|1998-01-21|Univ Manchester|Method and apparatus for detecting an object|
    CA2319454C|1998-02-11|2010-04-27|Non-Invasive Technology, Inc.|Detection, imaging and characterization of breast tumors|
    DE69937602T2|1998-02-11|2008-10-23|Non-Invasive Technology, Inc.|PICTURE GENERATION AND IDENTIFICATION OF BRAIN TISSUE|
    US6148226A|1998-02-13|2000-11-14|Aerospace Research Technologies Inc.|Optical imaging through scattering media: fit to an inhomogeneous diffusion model for differentiation|
    US6348942B1|1998-03-06|2002-02-19|The United States Of America As Represented By The Secretary Of The Army|Enhanced underwater visibility|
    JP3887486B2|1998-05-26|2007-02-28|浜松ホトニクス株式会社|Method and apparatus for measuring internal characteristic distribution of scattering medium|
    US6327489B1|1998-06-25|2001-12-04|U.S. Philips Corporation|Method of localizing an object in a turbid medium|
    US6332093B1|1998-08-06|2001-12-18|Art Recherches Et Technologies Avancees Inc./Art Advanced Research Technologies, Inc.|Scanning module for imaging through scattering media|
    US7904139B2|1999-08-26|2011-03-08|Non-Invasive Technology Inc.|Optical examination of biological tissue using non-contact irradiation and detection|
    AT314638T|1998-10-07|2006-01-15|Ecole Polytech|METHOD FOR THE LOCAL AND SURFACE MEASUREMENT OF THE SPREAD AND ABSORPTION CHARACTERISTICS OF TRUE MEDIA|
    US6678541B1|1998-10-28|2004-01-13|The Governmemt Of The United States Of America|Optical fiber probe and methods for measuring optical properties|
    US6404497B1|1999-01-25|2002-06-11|Massachusetts Institute Of Technology|Polarized light scattering spectroscopy of tissue|
    JP5047432B2|1999-09-14|2012-10-10|ザリサーチファウンデーションオブステイトユニバーシティオブニューヨーク|Method and system for imaging the dynamics of scattering media|
    US7046832B1|1999-09-14|2006-05-16|The Research Foundation Of State Univ. Of New York|Imaging of scattering media using relative detector values|
    US6795195B1|1999-09-14|2004-09-21|Research Foundation Of State University Of New York|System and method for tomographic imaging of dynamic properties of a scattering medium|
    JP4913299B2|1999-09-14|2012-04-11|ザリサーチファウンデーションオブステイトユニバーシティオブニューヨーク|Scattering medium imaging using relative detector values|
    AU7829500A|1999-09-17|2001-04-17|General Hospital Corporation, The|Calibration methods and systems for diffuse optical tomography and spectroscopy|
    JP2003531515A|2000-04-07|2003-10-21|ザ・リージェンツ・オブ・ジ・ユニバーシティ・オブ・カリフォルニア|Remote interrogation high data rate free space laser communication link|
    US7418118B2|2000-11-10|2008-08-26|Furnas Steven J|Method and apparatus for diagnosing pathogenic or allergenic microorganisms or microparticles at a remote location|
    US7274446B2|2001-04-07|2007-09-25|Carl Zeiss Jena Gmbh|Method and arrangement for the deep resolved optical recording of a sample|
    JP4259879B2|2001-05-17|2009-04-30|ゼノジェンコーポレイション|Method and apparatus for determining the depth, brightness and size of a target within a body region|
    US7596404B2|2001-06-28|2009-09-29|Chemimage Corporation|Method of chemical imaging to determine tissue margins during surgery|
    US7428434B2|2001-07-27|2008-09-23|The Regents Of The Univeristy Of California|Quantitative broadband absorption and scattering spectroscopy in turbid media by combined frequency-domain and steady state methodologies|
    US8066678B2|2001-12-17|2011-11-29|Bard Access Systems, Inc.|Safety needle with collapsible sheath|
    US6825928B2|2001-12-19|2004-11-30|Wisconsin Alumni Research Foundation|Depth-resolved fluorescence instrument|
    US7474398B2|2002-02-22|2009-01-06|Xenogen Corporation|Illumination system for an imaging apparatus with low profile output device|
    US6958815B2|2002-03-19|2005-10-25|The Regents Of The University Of California|Method and apparatus for performing quantitative analysis and imaging surfaces and subsurfaces of turbid media using spatially structured illumination|
    EP2410315B1|2002-06-04|2020-04-01|Visen Medical, Inc.|Imaging volumes with arbitrary geometries in contact and non-contact tomography|
    US7840257B2|2003-01-04|2010-11-23|Non Invasive Technology, Inc.|Examination of biological tissue using non-contact optical probes|
    DE10254139A1|2002-11-15|2004-05-27|Carl Zeiss Jena Gmbh|Method and arrangement for the depth-resolved optical detection of a sample|
    US20040147830A1|2003-01-29|2004-07-29|Virtualscopics|Method and system for use of biomarkers in diagnostic imaging|
    EP1593095B1|2003-02-05|2019-04-17|The General Hospital Corporation|Method and system for free space optical tomography of diffuse media|
    WO2005008195A2|2003-07-16|2005-01-27|Mcgill University|Quantification of optical properties in scattering media using fractal analysis of photon distribution measurements|
    US8082015B2|2004-04-13|2011-12-20|The Trustees Of The University Of Pennsylvania|Optical measurement of tissue blood flow, hemodynamics and oxygenation|
    US7304724B2|2004-04-13|2007-12-04|The Regents Of The University Of California|Method and apparatus for quantification of optical properties of superficial volumes|
    WO2005107843A1|2004-04-30|2005-11-17|C.R. Bard, Inc.|Valved sheath introducer for venous cannulation|
    WO2006105259A2|2004-07-30|2006-10-05|Novalux, Inc.|System and method for driving semiconductor laser sources for displays|
    TWM265652U|2004-08-03|2005-05-21|Premier Image Technology Corp|Solid integration rod for DLP|
    EP1827238A4|2004-12-06|2009-04-22|Cambridge Res & Instrmnt Inc|Systems and methods for in-vivo optical imaging and measurement|
    GB0426993D0|2004-12-09|2005-01-12|Council Cent Lab Res Councils|Apparatus for depth-selective raman spectroscopy|
    US7729750B2|2005-01-20|2010-06-01|The Regents Of The University Of California|Method and apparatus for high resolution spatially modulated fluorescence imaging and tomography|
    US8185176B2|2005-04-26|2012-05-22|Novadaq Technologies, Inc.|Method and apparatus for vasculature visualization with applications in neurosurgery and neurology|
    US7570988B2|2005-05-02|2009-08-04|Wisconsin Alumni Research Foundation|Method for extraction of optical properties from diffuse reflectance spectra|
    GB0606891D0|2006-04-05|2006-05-17|Council Cent Lab Res Councils|Raman Analysis Of Pharmaceutical Tablets|
    US8014569B2|2006-10-30|2011-09-06|The Regents Of The University Of California|Method and apparatus for performing qualitative and quantitative analysis of produce using spatially structured illumination|
    RU2009124456A|2006-11-28|2011-01-10|Конинклейке Филипс Электроникс Н.В. |METHOD AND DEVICE, MEDICAL DEVICE FOR PREPARING AN IMAGE FOR DISPLAYING THE INTERNALITY OF A MOTIONAL ENVIRONMENT WITH MEASUREMENT OF THE DARKNESS LEVEL|
    CA2682826C|2007-04-02|2013-08-13|Fio Corporation|System and method of deconvolving multiplexed fluorescence spectral signals generated by quantum dot optical coding technology|
    US7692160B2|2007-05-31|2010-04-06|General Electric Company|Method and system of optical imaging for target detection in a scattering medium|
    US7688448B2|2007-06-01|2010-03-30|University Of Utah Research Foundation|Through-container optical evaluation system|
    GB0717481D0|2007-09-07|2007-10-17|Angiomed Ag|Self-expansible stent with radiopaque markers|
    US8509879B2|2007-11-06|2013-08-13|The Regents Of The University Of California|Apparatus and method for widefield functional imaging using integrated structured illumination and laser speckle imaging|
    US20100210931A1|2008-04-04|2010-08-19|Modulate Imaging Inc.|Method for performing qualitative and quantitative analysis of wounds using spatially structured illumination|
    WO2009149178A1|2008-06-05|2009-12-10|Trustees Of Boston University|System and method for producing an optically sectioned image using both structured and uniform illumination|
    US8301216B2|2008-12-23|2012-10-30|The Regents Of The University Of California|Method and apparatus for quantification of optical properties of superficial volumes using small source-to-detector separations|
    EP2480876A4|2009-09-22|2017-10-25|Polyvalor, Limited Partnership|Method and system for optical data acquisition and tomography imaging of a turbid medium object|
    US8505209B2|2009-10-27|2013-08-13|N.E. Solutionz, Llc|Skin and wound assessment tool|
    US9161716B2|2009-10-27|2015-10-20|N.E. Solutionz, Llc|Diagnostic imaging system for skin and affliction assessment|
    US8276287B2|2009-10-27|2012-10-02|N.E. Solutionz, Llc|Skin and wound assessment tool|
    EP2501288B1|2009-11-19|2016-12-21|Modulated Imaging Inc.|Method and apparatus for analysis of turbid media via single-element detection using structured illumination|
    GB0921477D0|2009-12-08|2010-01-20|Moor Instr Ltd|Apparatus for measuring blood parameters|
    CN102665559B|2009-12-21|2015-06-24|泰尔茂株式会社|Excitation, detection, and projection system for visualizing target cancer tissue|
    US8606032B2|2009-12-23|2013-12-10|Sony Corporation|Image processing method, device and program to process a moving image|
    US7884933B1|2010-05-05|2011-02-08|Revolutionary Business Concepts, Inc.|Apparatus and method for determining analyte concentrations|
    USD662122S1|2011-04-07|2012-06-19|ARANZ Medical Limited|Combined handheld laser and camera unit|
    WO2013190391A2|2012-06-21|2013-12-27|Novadaq Technologies Inc.|Quantification and analysis of angiography and perfusion|
    ES2787384T3|2012-11-07|2020-10-16|Modulated Imaging Inc|Efficient modulated imaging|ES2787384T3|2012-11-07|2020-10-16|Modulated Imaging Inc|Efficient modulated imaging|
    US9456201B2|2014-02-10|2016-09-27|Microsoft Technology Licensing, Llc|VCSEL array for a depth camera|
    US9717417B2|2014-10-29|2017-08-01|Spectral Md, Inc.|Reflective mode multi-spectral time-resolved optical imaging methods and apparatuses for tissue classification|
    US20160235372A1|2015-02-17|2016-08-18|Telebyte, Inc.|Portable cancer diagnostic device and system|
    CA2977073A1|2015-02-23|2016-09-01|Li-Cor, Inc.|Fluorescence biopsy specimen imager and methods|
    EP3869184A1|2015-06-26|2021-08-25|Li-Cor, Inc.|Fluorescence biopsy specimen imager and methods|
    US10624533B2|2015-10-16|2020-04-21|Capsovision Inc|Endoscope with images optimized based on depth map derived from structured light images|
    US20170116762A1|2015-10-21|2017-04-27|Carestream Health, Inc.|Apparatus and method for scattered radiation correction|
    CN105510253B|2015-12-05|2019-03-01|浙江大学|With the device and method of spatial frequency domain image checking farm product tissue optical characteristics|
    CN109154558A|2016-02-12|2019-01-04|调节成像公司|Method and apparatus for assessing tissue vascular health|
    WO2017166082A1|2016-03-30|2017-10-05|温州医科大学|Rapid non-destructive tissue biopsy method and technique for large area resolution of microstructure based on spatial frequency domain modulation|
    EP3446098A1|2016-04-21|2019-02-27|Li-Cor, Inc.|Multimodality multi-axis 3-d imaging|
    US10278586B2|2016-06-23|2019-05-07|Li-Cor, Inc.|Complementary color flashing for multichannel image presentation|
    US10842422B2|2016-07-21|2020-11-24|University Of Kentucky Research Foundation|Compact low-cost fiberless diffuse speckle contrast flow-oximeter|
    CN110178014A|2016-11-14|2019-08-27|美国西门子医学诊断股份有限公司|Method and apparatus for using patterned illumination characterization sample|
    EP3545488A1|2016-11-23|2019-10-02|Li-Cor, Inc.|Motion-adaptive interactive imaging method|
    CN110573066A|2017-03-02|2019-12-13|光谱Md公司|Machine learning systems and techniques for multi-spectral amputation site analysis|
    EP3573521A4|2017-03-22|2020-12-09|Modulated Imaging Inc.|Systems and methods for assessing diabetic circulatory complications|
    WO2018200261A1|2017-04-25|2018-11-01|Li-Cor, Inc.|Top-down and rotational side view biopsy specimen imager and methods|
    CN107752981B|2017-10-30|2019-08-06|温州医科大学|A kind of optical imaging method based on layer structure mapping|
    US10720755B2|2018-02-07|2020-07-21|Elfi-Tech Ltd.|Ensemble-averaged measurement of stochastic motion by current-modulating of VCSEL wavelength|
    US10783632B2|2018-12-14|2020-09-22|Spectral Md, Inc.|Machine learning systems and method for assessment, healing prediction, and treatment of wounds|
    US10740884B2|2018-12-14|2020-08-11|Spectral Md, Inc.|System and method for high precision multi-aperture spectral imaging|
    法律状态:
    2018-03-06| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2018-03-13| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
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    优先权:
    申请号 | 申请日 | 专利标题
    US201261723721P| true| 2012-11-07|2012-11-07|
    US61/723,721|2012-11-07|
    US201361793331P| true| 2013-03-15|2013-03-15|
    US61/793,331|2013-03-15|
    PCT/US2013/068956|WO2014074720A1|2012-11-07|2013-11-07|Efficient modulated imaging|
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