WO2018148805A1 - System and a method for detecting a material in region of interest - Google Patents
System and a method for detecting a material in region of interest Download PDFInfo
- Publication number
- WO2018148805A1 WO2018148805A1 PCT/AU2018/050129 AU2018050129W WO2018148805A1 WO 2018148805 A1 WO2018148805 A1 WO 2018148805A1 AU 2018050129 W AU2018050129 W AU 2018050129W WO 2018148805 A1 WO2018148805 A1 WO 2018148805A1
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- WIPO (PCT)
- Prior art keywords
- region
- interest
- depth image
- property
- deposit
- Prior art date
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Classifications
-
- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T7/00—Image analysis
- G06T7/0002—Inspection of images, e.g. flaw detection
- G06T7/0012—Biomedical image inspection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B3/00—Apparatus for testing the eyes; Instruments for examining the eyes
- A61B3/10—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions
- A61B3/102—Objective types, i.e. instruments for examining the eyes independent of the patients' perceptions or reactions for optical coherence tomography [OCT]
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
- G01B9/00—Measuring instruments characterised by the use of optical techniques
- G01B9/02—Interferometers
- G01B9/02001—Interferometers characterised by controlling or generating intrinsic radiation properties
- G01B9/02011—Interferometers characterised by controlling or generating intrinsic radiation properties using temporal polarization variation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
- G01B9/00—Measuring instruments characterised by the use of optical techniques
- G01B9/02—Interferometers
- G01B9/02041—Interferometers characterised by particular imaging or detection techniques
- G01B9/02044—Imaging in the frequency domain, e.g. by using a spectrometer
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
- G01B9/00—Measuring instruments characterised by the use of optical techniques
- G01B9/02—Interferometers
- G01B9/0209—Low-coherence interferometers
- G01B9/02091—Tomographic interferometers, e.g. based on optical coherence
-
- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T7/00—Image analysis
- G06T7/50—Depth or shape recovery
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01B—MEASURING LENGTH, THICKNESS OR SIMILAR LINEAR DIMENSIONS; MEASURING ANGLES; MEASURING AREAS; MEASURING IRREGULARITIES OF SURFACES OR CONTOURS
- G01B2290/00—Aspects of interferometers not specifically covered by any group under G01B9/02
- G01B2290/70—Using polarization in the interferometer
-
- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T2207/00—Indexing scheme for image analysis or image enhancement
- G06T2207/10—Image acquisition modality
- G06T2207/10028—Range image; Depth image; 3D point clouds
-
- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T2207/00—Indexing scheme for image analysis or image enhancement
- G06T2207/10—Image acquisition modality
- G06T2207/10072—Tomographic images
- G06T2207/10101—Optical tomography; Optical coherence tomography [OCT]
-
- G—PHYSICS
- G06—COMPUTING; CALCULATING OR COUNTING
- G06T—IMAGE DATA PROCESSING OR GENERATION, IN GENERAL
- G06T2207/00—Indexing scheme for image analysis or image enhancement
- G06T2207/30—Subject of image; Context of image processing
- G06T2207/30004—Biomedical image processing
- G06T2207/30041—Eye; Retina; Ophthalmic
Definitions
- the present disclosure relates generally to a system and a method for detecting a material in region of interest and relates specifically, though not exclusively, to a system and method for detection of deposits within the region of interest and using polarization-sensitive optical coherence tomography ("PS OCT”) .
- PS OCT polarization-sensitive optical coherence tomography
- BM-RPE retinal pigment epithelium - Bruch' s membrane complex
- SLP Scanning laser polarimetry
- 2D face two-dimensional
- the present invention provides technological advancement.
- a method for detecting a material in a region of interest comprising:
- the method typically also comprises determining a threshold of the property. Determining the threshold of the property may comprise comparing depth images or depth image areas having the property, but which are not associated with the material with depth images or depth image areas having the property, but which are not associated with the material. In this case the depth images may be reference depth images of known regions of interest .
- the step of processing the at least one depth image using the pre-determined threshold may comprise comparing the at least one obtained depth image with (a library of) reference depth images to determine if the obtained depth image has a property below or above the pre-threshold .
- the step of processing the at least one depth image using the pre-determined threshold may comprise filtering out or
- the step of detecting the material in the region of interest may comprise analyzing the processed at least one depth image.
- the step of providing at least one depth image may comprise using OCT imaging of the region of interest.
- the OCT imaging may be PS OCT.
- the material may be a deposit.
- the step of providing the at least one depth image may be performed in-vivo or ex-vivo.
- the step of providing the at least one depth image is performed in-vivo and the region of interest is a region of interest of a subject, such as a patient.
- the region of interest may be a region within an eye of the subject, such as the retinal pigment epithelium of a subject's eye and the deposit may be a deposit within the in the retinal pigment epithelium (such as BM-RPE) .
- the property may be a local intensity of an area or pixels within the at least one depth image.
- the property is a retardance of electromagnetic waves as detectable with PS OCT (for example, by determining a change in polarization angle relative to a reference) .
- the OCT imaging may be PS OCT and may use a reference at an interface with a deposit at a location below or above the deposit.
- the deposit is a deposit in the retinal pigment epithelium - Bruch' s membrane complex of a subject's eye.
- An inner or outer segment of a photoreceptor layer may be used as a reference.
- the method may be conducted to detect deposits located in a retinal pigment epithelium - Bruch' s membrane complex of a subject's eye (such as in the BM-RPE) by detecting associated retardance. Further, the method may be conducted to detect retardance induced by a further deposit that is located below another deposit using at least one reference that is positioned above the at least one the other deposit.
- a system for detecting a material in region of interest the system being configured to:
- the system typically is also configured to determine the threshold of the property of associated with the at least one depth image.
- a non-transitory computer-accessible medium having stored thereon computer-executable instructions for detecting a material in region of interest, the computer arrangement being configured to perform procedures comprising:
- the computer-accessible medium may be configured to utilize inner and outer segments of a photoreceptor layer as a reference to collect the at least one retardance located below a retinal pigment epithelium (such as BM-RPE) .
- a retinal pigment epithelium such as BM-RPE
- a non-transitory computer-accessible medium having stored thereon computer-executable instructions for detecting at least one deposit in at least one subject, wherein, when a computer arrangement executes the instructions, the computer arrangement is configured to perform procedures comprising:
- the computer arrangement may be further configured to detect at least one retardance induced by a further deposit that is located below or above the at least one deposit using at least one reference that is positioned above or below the at least one deposit.
- the computer arrangement may also be configured to utilize inner and outer segments of a photoreceptor layer as a reference to collect the at least one retardance for a region below a retinal pigment epithelium (such as BM-RPE) .
- the computer arrangement may be configured to determine the at least one deposit using at least one light source having a central wavelength. The central wavelength may be about 840 nm.
- the computer arrangement may be further configured to detect the at least one deposit using a polarization having adaptive optics .
- a method for detecting at least one deposit in at least one subject comprising:
- Figure 1 is a diagram of an exemplary spectral-domain Polarization-sensitive optical coherence tomography system according to an embodiment of the present invention
- Figures 2-3 are flow diagrams of a method of detecting a deposition according to an embodiment of the present invention
- Figure 4 is a histogram illustrating data obtained using a method in accordance with an embodiment of the present
- Figure 5 and 6 are images illustrating data obtained using a method in accordance with an embodiment of the present
- Figures 7A-7D are images produced using the system and method according to an embodiment of the present invention.
- Figures 8A-8K are further exemplary images produced using the system and method according to an embodiment of the present invention.
- Figure 9 is an exemplary block diagram of a system in accordance with embodiments of the present invention.
- FIG. 1 shows a diagram of a spectral-domain PS-OCT system 100 according to an embodiment of the present disclosure.
- the system 100 has a source arm 102 with a broadband light source 104. Further, the system 100 has a reference arm 106.
- the broadband light source 104 emits light within a wavelength range centered around (840nm) .
- the source arm 102 light can be sent from the broadband light source 104 through an isolator 105 and two glass slides 107 for calibration. These glass slides can also be mounted in other arms of the
- the interferometer such as the reference arm 106.
- Information regarding the light can then proceed through a polarization modulator 110.
- the modulator 110 can apply two or more
- Polarization controllers 116 are used to set the polarization state.
- the light is then split by a single-mode fiber coupler 118.
- the reference arm 106 includes in this example a polarizer 122 and a mirror 124.
- the polarizer 122 is used in combination with the polarization controller 116 to ensure that the power returning to a detector can be the same for each polarization state, at each instant (e.g., even and odd depth scans, obtained with orthogonal input states) .
- the system 100 also has a sample arm 126 that includes in this example a raster scanning device 128 arranged to scan the retina of a subject.
- the system 100 further has a detection arm 130.
- the detection arm 130 has in this example a polarization-sensitive high-speed spectrometer with a collimator 132, a transmission grating 134, a Wollaston prism 136, a focusing lens system 138 and line-scan camera 140.
- Detected spectra can be mapped to k-space, can be dispersion compensated, such that they can be Fourier
- FIGS. 2 and 3 show flow diagrams of a method 200 of detecting a deposit in a subject's eye according to an embodiment of the present invention.
- the method 200 includes step 202, which uses OCT intensity images for automatic image segmentation of the inner and outer segments of the photoreceptor layer ("IS/OS") and the bottom of the RPE-BM complex of the subject's eye.
- Step 204 retrieves (virtual) reference and measurement points and step 250 performs a measurement for the bottom layer of the RPE- BM complex.
- the bottom edge of this complex can be detected in healthy subjects and subjects with minor drusen by offsetting the IS/OS by 66 ⁇ .
- Step 248 used the IS/OS as a reference, as it usually provides high reflectivity, and is the closest reflector to the deposits in the RPE-BM complex.
- a double pass phase retardation (“DPPR") is calculated using Stokes-vector analysis with respect to the IS/OS as illustrated in flow chart shown in Figure 3.
- Step 252 of the method 200 retrieves DPPR and collects the retardation induced by deposits at the bottom of the RPE/BM complex. The measured retardation at this depth includes contributions of the photoreceptor outer tips, RPE cells, BM and deposits in Bruch' s membrane.
- Step 254 of method 200 identifies retardance data points that are suspect using a "normal data base" with 10 young healthy suspects.
- Figure 4 is a histogram illustrating the data obtained from the 10 healthy subjects. This data was used to find a threshold at which data points become suspect. For example, the 99 th percentile (e.g., about 48.6°) was used to identify these points. At p99, the 99 percentile, a DPPR cut-off is only found to be in 1% of all data points.
- Figure 5 illustrates the data 500 obtained from 10 older subjects; two of these subjects, for example, subjects 13 and 14 (see e.g., identifiers in the top left corner of each panel) were diagnosed as AMD patients; all other subjects did not have AMD.
- suspect data points can be identified (see Figure 6, identified points or pixels shown in lighter colour) . While there were three other subjects with significantly elevated DPPR values these subjects were not diagnosed with AMD, showing that the exemplary method can identify data points that can be pre-clinical . These subjects likely have thin deposits in their RPE/BM complex that have not matured into drusen.
- Figures 7A-7D show images produced using the system and method according to an embodiment of the present invention.
- Figures show DPPR recorded below BM over about 15° by about 15° in a 59-year old subject in year 0 (e.g., Figure 3A) , and after one year (e.g., Figure 3B) .
- Figure 7A illustrates data obtained in a 55-year old in year 0, and Figure 7B shows the DPPR obtained after four years.
- the percentages above the images indicate how many data points were above the 99% cut-off of the 10 young subjects.
- threshold increased with time, illustrating an accumulation of deposits .
- Figures 7C and 7D show further exemplary images produced using the system and method according to an embodiment of the present invention.
- Figure 7C illustrates data obtained in a 61-year old in year 0, with 22.8% of data points above the threshold, indicating accumulation of deposits.
- Figure 7B shows the DPPR obtained after four years. Here, 19.8% of the data points were above the threshold.
- Figures 8A-8K show further images produced using the system and method according to an embodiment of the present invention.
- a druse can be found in the B-scan of subject 13 (e.g., Figure 8A) in frame 74 (e.g., the volume set has 100 frames) .
- Exemplary data was obtained with aPS-OCT system as described above with reference to Figures 1 to 3.
- the data was obtained on ten young healthy subjects and ten older subjects (e.g., 2-40) . Two of these older subjects were diagnosed with AMD; all other subjects were graded as healthy without AMD.
- the processing begins with i-space mapping and dispersion compensation.
- the real and imaginary parts of the acquired spectra can be converted into Stokes vectors.
- each pixel in an image has four Stokes vectors I, Q, U and V.
- the retardance is calculated with respect to a reference.
- the interface between the inner and outer segments of the photoreceptor layer was used as a reference to avoid contamination of the retardance signal with contributions by the PS-OCT system itself, the cornea, retinal nerve fiber layer, and Henle fiber layer.
- a goal of the measurement was to quantify the retardance induced by the RPE-BM complex, which is located just below this reference.
- the IS/OS reflect well, which provides a strong signal for reliable retardance calculation.
- An objective is to detect polarization changes induced by deposits, which can occur in the RPE-BM complex, and it is beneficial to find a reference that can be close to these deposits, without being too close such that some spatial averaging can be applied.
- a reference that can be, for instance, at the top of the retina would not provide the same information, as birefringence contributions from the RNFL and the Henle fiber layer can contaminate the measurement that can be aimed at deposits in the RPE-BM complex.
- the fast axis orientation of the RNFL can be used for retardance calculations, which can be different from the fast axis orientation of the tissue between the IS/OS and the RPE-BM complex, which can cause serious artifacts.
- the IS/OS is beneficial for this purpose.
- the top of the RPE can also be used, but, as it is more closely spaced to the bottom of the RPE-BM complex, spatial averaging of Stokes vectors (which can be used to filter out speckle noise
- the IS/OS is in this example automatically segmented with image processing software.
- the retardance induced with respect to the IS/OS can be calculated. This is performed such that a color-coded image is generated, ranging from about 0° to about 180°, that is at about 0° at the IS/OS (see step 252 in Figure 2) . In the direction towards the RNFL, and in the direction towards the choroid, an increase in DPPR is observed.
- the bottom of the RPE-BM complex can be of interest, as it can provide the retardance induced by deposits in the RPE-BM
- the bottom of the RPE-BM complex is found by an offset of about 66 pm in the downward direction from the segmented IS/OS.
- Automatic segmentation also provides the location of the bottom of the RPE-BM complex.
- the DPPR at this location can be
- Gaussian-shaped histogram shows the relationship between DPPR and percentiles: the 99 th percentile can be at a DPPR of 48.6°; the 99.9 th percentile can be at 67.8°. Depending on how strictly the data of patients can be thresholded, a certain cut-off to threshold data can be applied.
- the exemplary elevated retardance values are in this example linked to deposits.
- data sets obtained from two subjects, taken four and two years apart is shown in Figures 7A-7D.
- DPPR can be mainly concentrated in areas that already had the highest DPPR in year 0. Areas with deposits can be likely to block the flow of nutrients and waste material, thereby collecting more deposits over time.
- Figures 8A-8K illustrate the DPPR signal below the drusen.
- the drusen are comprised of "waste material", and can look like mounds.
- the exemplary DPPR signal below the center of a druse is low, well below the 99 percentile cut-off. At the edges of the druse, the DPPR signal is significantly higher.
- a distribution of the retardation that was recorded in the RPE- BM complex of ten young healthy subjects with spectral-domain PS-OCT at 840 nm is used to threshold data points that can be suspect, to identify areas with deposits in patients with age related macular degeneration or patients who are about to have age related macular degeneration.
- a reference for polarization-sensitive analysis can be located at the automatically segmented interface between the inner and outer segments of the photoreceptor layer (IS/OS); the retardance induced by deposits is recorded at or below the RPE-BM complex, which can either be found by an offset from the IS/OS, or by automatic image segmentation.
- the reference can alternatively also be located at the top of the RPE (towards the RNFL) .
- a reference higher up in the retina, for example, at the top of the RNFL can also be used as a reference. While it can provide less accurate measurements, it can still provide some signal in the RPE-BM complex. This can benefit from a re-calibration of the data set illustrated in Figure 4, to determine the cut-off for an accurate threshold to detect deposits.
- a spectral-domain system at any other central wavelength than 840 nm can be used (e.g. visible range, or near infra-red range near 1050 nm) .
- a swept-source PS-OCT system at any wavelength can be used.
- the exemplary system can be utilized with adaptive optics.
- Figure 6 shows a block diagram of an embodiment of a system according to the present invention.
- Procedures can be performed by a processing arrangement and/or a computing arrangement 605.
- Such processing/computing arrangement 605 can be, for example entirely or a part of, or include, but not limited to, a computer/processor 610 that can include, for example one or more microprocessors, and use instructions stored on a computer- accessible medium (e.g., RAM, ROM, hard drive, or other storage device) .
- a computer- accessible medium e.g., RAM, ROM, hard drive, or other storage device
- a computer-accessible medium 615 e.g., as described herein above, a storage device such as a hard disk, floppy disk, memory stick, CD-ROM, RAM, ROM, etc., or a collection thereof
- the computer-accessible medium 615 can contain executable instructions 620 thereon.
- a storage arrangement 625 can be provided separately from the computer-accessible medium 615, which can provide the instructions to the processing arrangement 605 so as to configure the processing arrangement to execute exemplary procedures, processes and methods, as described herein above .
- the exemplary processing arrangement 605 can be provided with or include an input/output arrangement 635, which can include, for example a wired network, a wireless network, the internet, an intranet, a data collection probe, a sensor, etc.
- the exemplary processing arrangement 605 is in communication with an exemplary display arrangement 630, which, can be a touch-screen configured for inputting information to the processing arrangement in addition to outputting information from the processing arrangement, for example.
- the exemplary display 630 and/or a storage arrangement 625 can be used to display and/or store data in a user-accessible format and/or user-readable format.
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Abstract
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Priority Applications (5)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP18754934.0A EP3582677B1 (en) | 2017-02-17 | 2018-02-16 | System and a method for detecting a material in region of interest |
JP2019542382A JP2020508094A (en) | 2017-02-17 | 2018-02-16 | System and method for detecting material in a region of interest |
US16/485,193 US20200043161A1 (en) | 2017-02-17 | 2018-02-16 | System and a method for detecting a material in region of interest |
AU2018221899A AU2018221899A1 (en) | 2017-02-17 | 2018-02-16 | System and a method for detecting a material in region of interest |
DK18754934.0T DK3582677T3 (en) | 2017-02-17 | 2018-02-16 | SYSTEM AND METHOD FOR DETECTING A MATERIAL IN THE AREA OF INTEREST |
Applications Claiming Priority (2)
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US201762460384P | 2017-02-17 | 2017-02-17 | |
US62/460,384 | 2017-02-17 |
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WO2018148805A1 true WO2018148805A1 (en) | 2018-08-23 |
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PCT/AU2018/050129 WO2018148805A1 (en) | 2017-02-17 | 2018-02-16 | System and a method for detecting a material in region of interest |
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US (1) | US20200043161A1 (en) |
EP (1) | EP3582677B1 (en) |
JP (1) | JP2020508094A (en) |
AU (1) | AU2018221899A1 (en) |
DK (1) | DK3582677T3 (en) |
WO (1) | WO2018148805A1 (en) |
Citations (4)
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WO2010085618A1 (en) * | 2009-01-23 | 2010-07-29 | Indiana University Research And Technology Corporation | Devices and methods for polarization-sensitive optical coherence tomography with adaptive optics |
WO2010122118A1 (en) * | 2009-04-24 | 2010-10-28 | Ursula Schmidt-Erfurth | Method for determining exudates in the retina |
EP2896355A1 (en) * | 2014-01-21 | 2015-07-22 | Kabushiki Kaisha Topcon | Geographic atrophy identification and measurement |
AU2015201992A1 (en) * | 2015-04-21 | 2016-11-10 | Canon Kabushiki Kaisha | Method, system and apparatus for determining abnormal structures of biological tissue layers of a retina |
Family Cites Families (4)
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JP4162242B2 (en) * | 2005-01-28 | 2008-10-08 | 富士フイルムRiファーマ株式会社 | Diagnostic imaging support system |
JP2016093240A (en) * | 2014-11-12 | 2016-05-26 | キヤノン株式会社 | Image processing apparatus and image processing method |
JP6685706B2 (en) * | 2015-01-07 | 2020-04-22 | キヤノン株式会社 | Image processing apparatus and image processing method |
US10117568B2 (en) * | 2015-01-15 | 2018-11-06 | Kabushiki Kaisha Topcon | Geographic atrophy identification and measurement |
-
2018
- 2018-02-16 WO PCT/AU2018/050129 patent/WO2018148805A1/en unknown
- 2018-02-16 AU AU2018221899A patent/AU2018221899A1/en not_active Abandoned
- 2018-02-16 DK DK18754934.0T patent/DK3582677T3/en active
- 2018-02-16 JP JP2019542382A patent/JP2020508094A/en active Pending
- 2018-02-16 US US16/485,193 patent/US20200043161A1/en not_active Abandoned
- 2018-02-16 EP EP18754934.0A patent/EP3582677B1/en active Active
Patent Citations (4)
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WO2010085618A1 (en) * | 2009-01-23 | 2010-07-29 | Indiana University Research And Technology Corporation | Devices and methods for polarization-sensitive optical coherence tomography with adaptive optics |
WO2010122118A1 (en) * | 2009-04-24 | 2010-10-28 | Ursula Schmidt-Erfurth | Method for determining exudates in the retina |
EP2896355A1 (en) * | 2014-01-21 | 2015-07-22 | Kabushiki Kaisha Topcon | Geographic atrophy identification and measurement |
AU2015201992A1 (en) * | 2015-04-21 | 2016-11-10 | Canon Kabushiki Kaisha | Method, system and apparatus for determining abnormal structures of biological tissue layers of a retina |
Non-Patent Citations (3)
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GOTZINGER, E. ET AL.: "Retinal pigment epithelium segmentation by polarization sensitive optical coherence tomography", OPTICS EXPRESS, vol. 16, 21 October 2008 (2008-10-21), pages 16410 - 16422, XP009192229, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976032> [retrieved on 20180315] * |
PIRCHER, M. ET AL.: "Polarization sensitive optical coherence tomography in the human eye", PROGRESS IN RETINAL AND EYE RESEARCH, vol. 30, no. 6, November 2011 (2011-11-01), pages 431 - 451, XP028318331, Retrieved from the Internet <URL:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3205186> [retrieved on 20180315] * |
See also references of EP3582677A4 * |
Also Published As
Publication number | Publication date |
---|---|
DK3582677T3 (en) | 2021-12-13 |
EP3582677B1 (en) | 2021-10-13 |
US20200043161A1 (en) | 2020-02-06 |
JP2020508094A (en) | 2020-03-19 |
AU2018221899A1 (en) | 2019-08-15 |
EP3582677A1 (en) | 2019-12-25 |
EP3582677A4 (en) | 2019-12-25 |
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