WO2013007967A1 - Tomographie en cohérence optique dans le domaine de fourier - Google Patents

Tomographie en cohérence optique dans le domaine de fourier Download PDF

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Publication number
WO2013007967A1
WO2013007967A1 PCT/GB2012/000567 GB2012000567W WO2013007967A1 WO 2013007967 A1 WO2013007967 A1 WO 2013007967A1 GB 2012000567 W GB2012000567 W GB 2012000567W WO 2013007967 A1 WO2013007967 A1 WO 2013007967A1
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Prior art keywords
sample
diffusive material
sample surface
diffusive
optically
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PCT/GB2012/000567
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English (en)
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Mario Ettore Giardini
Nikola Krstajic
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University Court Of The University Of St Andrews
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Publication of WO2013007967A1 publication Critical patent/WO2013007967A1/fr

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    • 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
    • G01B9/02015—Interferometers characterised by the beam path configuration
    • G01B9/02017—Interferometers characterised by the beam path configuration with multiple interactions between the target object and light beams, e.g. beam reflections occurring from different locations
    • G01B9/02019—Interferometers characterised by the beam path configuration with multiple interactions between the target object and light beams, e.g. beam reflections occurring from different locations contacting different points on same face of object
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0062—Arrangements for scanning
    • A61B5/0066—Optical coherence imaging
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/44—Detecting, measuring or recording for evaluating the integumentary system, e.g. skin, hair or nails
    • A61B5/441—Skin evaluation, e.g. for skin disorder diagnosis
    • 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
    • G01B9/02055—Reduction or prevention of errors; Testing; Calibration
    • G01B9/02056—Passive reduction of errors
    • G01B9/02057—Passive reduction of errors by using common path configuration, i.e. reference and object path almost entirely overlapping
    • 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
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
    • G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
    • G01N21/47—Scattering, i.e. diffuse reflection
    • G01N21/4795—Scattering, i.e. diffuse reflection spatially resolved investigating of object in scattering medium
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/72—Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7235—Details of waveform analysis
    • A61B5/7253—Details of waveform analysis characterised by using transforms
    • A61B5/7257—Details of waveform analysis characterised by using transforms using Fourier transforms

Definitions

  • the present invention relates to a system and method for implementing Fourier- domain optical coherence tomography.
  • OCT optical coherence tomography
  • OCT Fourier-domain Optical Coherence Tomography
  • Michelson interferometers In a family of typical configurations, known as spectrometer-based OCT, light from a low optical coherence (i.e. broadband) source is split into two arms. The length of one arm (the reference arm) is defined by a mirror and is kept fixed. On the other arm, the mirror is replaced by the sample that backscatters light into the interferometer. The light from the two arms is recombined, and only the light that has been backscattered can interfere, giving different interference , depending on the coherence length of the source and on the . difference between the reference arm length and the scattering depth. Such coherence length is determined by the .
  • swept- source laser OCT In a family of configurations known as swept- source laser OCT, a frequency-swept narrowband source (for .example, a wave/ength- swept laser) is used to explore the spectrum sequentially. Again, the length of the reference arm is defined by a mirror and is kept fixed, and the sample backscatters light. These techniques are jointly referred to as Fourier-domain Optical Coherence Tomography (FDOCT). The backscattering profile is calculated as a Fourier transform of the interpolated spectrum.
  • FDOCT Fourier-domain Optical Coherence Tomography
  • OCT is intrinsically non-invasive and exhibits great potential in in-vivo measurements, where it complements more traditional technologies, such as ultrasound imaging, by employing a different contrast mechanism and , by offering higher resolution, at the expense of a much lower penetration depth.
  • the conceptual simplicity, of the OCT probes essentially consisting of optical coupling elements between a scattering medium and an interferometer arm, leads to applications in multiple fields, such as, for example, those mentioned before.
  • a problem facing any implementation is the optical length of the sample arm, which needs to be carefully matched with the optical length of the reference arm for every wavelength covered by the broadband or swept source laser employed. This is typically done by matching both the geometrical length and the dispersion of the two arms.
  • one or both arms are implemented using optical fibres, such as in endoscopic or laparoscopic applications, fibre bending, temperature variations and polarization fading affect light propagation in the fibres so simple static dispersion matching does not always produce good results.
  • US 7821643 describes a common path frequency domain OCT system that uses non- specular reference reflection for obtaining internal depth profiles and depth resolved images of samples.
  • This has an optical fibre probe for delivering light to a sample and a partially optically transparent non-specular reflective optical element placed in the vicinity of the sample.
  • the partially optically transparent non-specular reflector is implemented as a coating placed on the interior surface of the optical probe window ⁇ including spots of a metal, or a dielectric coating, separated by elements of another ? coating.
  • a problem with this arrangement is that the width of the probe window reduces the depth to which images can be captured.
  • a Fourier-domain OCT system for capturing images of a sample, the system comprising an interferometer that has a reference arm and a sample arm, wherein in use the reference arm uses the sample surface or an optically diffusive material applied to the sample surface as a reflector.
  • a patient's skin is itself used as the reference backscattering surface.
  • the ability to use skin as part of the reference arm is unexpected, as skin reflectance and scattering has for a considerable time been perceived as a problem that has to be avoided, and many techniques have been proposed to remove its effects.
  • the term "backscattering” is often indicated as “diffuse reflectance”. In the context of the present application, "diffusive” is intended to mean “giving rise to backscattering/diffuse reflectance”.
  • a diffusive material may be applied to the sample surface, and provide a backscattered reference signal when applied to the sample surface that has a power or intensity that ⁇ is greater than that of the sample surface alone.
  • the diffusive material is not absorbable by the sample.
  • the diffusive , material may be preferably selected from: aluminium hydroxide and/or other aluminium oxides, titanium oxides, barium sulphate, polymer powders, chalk, talcum, gypsum, sandarac.
  • the diffusive material may be a powder.
  • the diffusive material may be combined with a dispersive medium.
  • the dispersive medium may comprise: a gel or a liquid.
  • the dispersive medium may comprise petroleum jelly, water, alcohols.
  • a gaseous application vector may be employed (e.g>, for spraying).
  • the optically diffusive material may be combined with a pharmaceutical compound ' (such., as for example, a drug for photodynamic therapy, a vasodilator, a vasocpnstrictor, an anaesthetic).
  • a pharmaceutical compound ' such., as for example, a drug for photodynamic therapy, a vasodilator, a vasocpnstrictor, an anaesthetic.
  • the optically diffusive material may be combined with an optical sample clearing substance (e.g. glycerol or urea) to provide better light penetration.
  • an optical sample clearing substance e.g. glycerol or urea
  • a method for capturing Fourier-domain OCT images of tissue through skin comprising illuminating a reference arm and a sample arm of an interferometer, wherein the reflective part of the reference arm comprises the skin or a diffusive material applied to the skin, and processing light reflected from the skin and the sample tissue to produce an image.
  • Figure 1 is a schematic diagram of a Fourier-domain common path spectrometer-based OCT system
  • Figures 2(a) and 2(b) show OCT. images of skin at 50 ⁇ and 250 ⁇ CCD integration time where inherent diffuse reflection of skin is used;
  • Figures 2(c) and 2(d) show the OCT images of skin at 50 ⁇ and 250 ⁇ CCD integration time where aluminium hydroxide (ATH) powder is mildly rubbed on the surface of skin;
  • ATH aluminium hydroxide
  • Figure 3 is a plot of surface reflectance versus depth for one image acquired with ATH and one image acquired without ATH; .
  • Figure 4 shows a common path OCT image derived from tissue reference arm overlaid with one from a separate reference arm
  • Figures 5(a) and 5(b) show the OCT images of an onion sample at 50 ⁇ integration time where inherent diffuse reflection (5(a)) is used, and where ATH powder is mildly rubbed on the surface of the sample.
  • Figure 1 (a) shows a Fourier domain OCT system that has a common path configuration, i.e. the reference and the sample arm of the interferometer follow a common path.
  • the system has an optical source, in this case a superluminescent diode (SLED371-HP1 , Superlum Diodes, Russia), and a custom-made spectrometer, each of which are connected to an optical fibre.
  • the optical fibres are connected via a fibre coupler (e.g. a 3dB fibre coupler) to a single mode fibre (SMF) that is in turn connected to an objective for directing light onto a target sample and receiving light reflected from the sample. Due to its common path configuration, the single mode. fibre can be of arbitrary length.
  • SMF single mode fibre
  • the fibre of the common arm does not have a reflector at its end for reflecting the reference signal. Instead, the sample surface is used as the zero path length reference point.
  • the backscattered spectrum from the common arm is detected by the spectrometer that has dispersive optics and a spatially-resolved detector (for example, a line CCD camera Aviiva EM1).
  • the system of Figure 1 (a) uses the sample surface, in this case, the skin, as the zero path length reference point, by employing as reference the light reflected or backscattered by the sample surface itself.
  • a reflective or diffusive compound can be applied directly to the tissue surface (see Figure 1 (b)). This arrangement naturally avoids complex conjugate mirror artefacts. Though layers of any thickness can be applied, only a thin layer ( ⁇ 200 ⁇ ) of compound is needed to provide high depth of field (DOF) imaging of the sample.
  • the power or intensity of light backscattered from the skin surface has to be greater than the light backscattered from the skin. If this condition is satisfied, then interference between the backscattered reference light and light backscattered from the sample results in amplification of the backscattered sample signal. Assessing this can be done by experimentation. If an image of a sample can be seen, it can be assumed that the reference signal is of sufficient, strength. If an image of the sample cannot be seen or the sample image needs to be of a better quality, then a diffusive material can be applied directly to the skin or the quantity of material could be varied or the type of diffusive material could be varied to improve image quality.
  • light from the source passes through the objective and towards the sample, - where some of the light is reflected or backscattered back from the sample surface (optionally coated by the diffusive compound) and used as a reference, and some passes into the sample.
  • Light reflected or backscattered from, the sample is transmitted to the spectrometer where it is processed together with the reference light.
  • Using reflections or backscattering from the sample surface as a reference means that the reference . and the sample backscattering are intrinsically co-aligned for collection by the coupling optics to the common arm of the splitter.
  • FDOCT signal is normally described as follows (see R. A. Leitgeb and . Wojtkowski, "Complex and Coherence Noise Free Fourier Domain Optical Coherence Tomography,” in Optical Coherence Tomography, W. Drexler and J. G. Fujimoto, eds. (Springer Berlin Heidelberg, 2008), pp. 177-207), the contents of which are incorporated by reference): ( 1 ) p. and p . are the complex reflection coefficients of layers within sample, while p Js the complex reflection coefficient of the reference arm. r(r) is the coherence function of the source.
  • the second and third terms are the ' autocorrelation terms describing sample signals interfering with each other. The last two terms normally provide the two mirror images of the useful OCT signal.
  • the "reference arm” is physically the surface of the sample. This can be viewed as removing the last two terms of Equation (1 ) above while exploiting the useful the part of the autocorrelation signal that contains the structure of the sample. Unwanted DC terms will potentially affect the very top areas of the resulting OCT image, but simple background subtraction can be employed to minimize this.
  • Figure 2 shows various images of tissue taken with and without a diffusive substance applied to skin. In initial experiments, the diffuse substance used was aluminium hydroxide (ATH).
  • Figures 2(a) and 2(b) show the OCT images of skin at 50 ⁇ and 250 ps CCD integration time where inherent diffuse reflection of the skin surface is used.
  • Figures 2(c) and 2(d) show the OCT images of skin at 50 ps and 250 ps CCD integration time where ATH powder is mildly rubbed on skin surface.
  • the thickness of ATH deposited was below 10 pm.
  • the images of Figure 2 are of a similar area of tissue, but movement between scans reduced the correspondence. In each case, the image size was 1 mm depth * 5 mm width.
  • the images are affected by variation in intensity of each individual lateral scan constituting the image (A-scan). This was compensated by local histogram equalization.
  • each image was divided into windows two columns (two A- scans) wide, which were individually processed with histogram equalization. Then all windows were merged back and optimized to same contrast levels, as in A. R. Tumtinson, J. K. Barton, B. Povazay, H. Sattman, A. Unterhuber, R. A. Leitgeb, and W. Drexler, "Endoscope-tip interferometer for ultrahigh resolution frequency domain optical coherence tomography in mouse colon," Opt. Express 14, 1878-1887 (2006), the contents of which are incorporated herein by reference. From Figure.2, it can be seen that the best quality image is in Figure 2(d), where deep dermal structures are visible. Figures 2(c) and 2(d) are of similar quality indicating that faster versions of imaging are possible. Nevertheless, inherent reflection of skin without a diffusive compound also enables good imaging.
  • Figure 3 compares light collected from the surface from two samples acquired with and without ATH. Both images had the same focusing conditions.
  • Standard OCT images were acquired using a separate dispersion-compensated arm and mirror, such as described in Ma.ciej Wojtkowski, Andrzej Kowalczyk, Tomasz Bajraszewski, Rainer Leitgeb and Adolf F. Fercher In vivo human retinal imaging by. Fourier domain optical coherence tomography. J. Biomed. Opt. 7, 457 (2002).
  • the images were compared only if the standard OCT images were at the same distance from the focal point as in the system of the invention (zero path' length), thus maintaining strict focus conditions. Average values were obtained by averaging the light collected on each image over the 1000 (A-scans) for each image. Background spectrum due to fibre end reflection was subtracted prior to: imaging, and thus did not contribute to such average values.
  • Figure 3 shows that skin with ATH has higher reflectance by >5dB and therefore is better as the reflector for the common path OCT reference arm.
  • Figure 4 shows a common path OCT image derived from tissue reference arm overlaid with one from a separate reference arm. The two images are substantially the samei demonstrating the effectiveness of the tissue surface common reference approach thereby exemplified.
  • an onion bulk sample has been imaged.
  • Figures 5(a) and 5(b) show the OCT images of the onion sample at 50 MS integration time where inherent diffuse reflection (5(a)) is used and where .
  • ATH powder is mildly rubbed on the sample surface (5(b)). From these Figures, it can be seen the cell walls are clearly visible, showing an unequivocally good contrast both with and without ATH. Whilst the images of Figure 5 show some improvement can be obtained with ATH, in fact both images are of a high quality.
  • Optical clearing of tissue is a well-established area, whereby various compounds are applied to the surface of whole organs to make them more transparent. They are made transparent for either visible or near-infrared light as these the main wavelengths used in microscopy and optical imaging in general.
  • a standard way of optically clearing skin is simply to apply glycerol on skin surface. This reduces reflection from the surface of the skin. After about 10 minutes glycerol physically diffuses into skin. There it replaces water by process called hyperosmosis.
  • the refractive index of glycerol is similar to the refractive index of surrounding tissue material so light tends to bend less.
  • the diffusive powder of the present invention could be combined with an optical clearing agent to improve the tissue surface self-referencing signal and simultaneously provide better depth penetration of light into the sample to provide the backscattered sample signal.
  • the present invention uses the sample surface to provide a self-referencing ⁇ backscattered signal and thereby avoids the complex conjugate mirror artefact that is problematic in most Fourier domain OCT systems. This provides a new approach to OCT imaging.
  • the invention has applications beyond structural OCT imaging, for example in Doppler OCT, and polarization sensitive OCT.
  • the diffusive compound is described as being ATH
  • other diffusive compounds such as, for example, aluminium oxides, titanium oxides, barium sulphate, polymer powders, chalk, gypsum, talcum, sandarac, could be used, provided they are not significantly absorbed by the sample within the measurement time.
  • the diffusive compound could be combined with a dispersive medium, such as, for example, in gel, liquid or gaseous form, that is not absorbed by the sample and that may subsequently stay in place or evaporate (e.g. petroleum jelly, water, alcohols).
  • the optical diffuse compound and/or the dispersive medium may have additional functions, such as, for example, act as a pharmaceutical compound (such, as for example, a drug for photodynamic therapy, a vasodilator, a vasoconstrictor, an anaesthetic), or as an optical sample clearing substance (e.g. glycerol or urea, eventually in solution) to provide better light penetration, or as a . arnish, or as an encapsulating compound, at the same time as keeping the surface diffusive/reflective.
  • a pharmaceutical compound such, as for example, a drug for photodynamic therapy, a vasodilator, a vasoconstrictor, an anaesthetic
  • an optical sample clearing substance e.g. glycerol or urea, eventually in solution

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Abstract

L'invention concerne un système de tomographie en cohérence optique dans le domaine de Fourier, destiné à capturer des images d'un échantillon. Ce système comprend un interféromètre pourvu d'un bras de référence et d'un bras d'échantillon, la partie réfléchissante du bras de référence comprenant la surface d'échantillon ou un matériau de diffusion optique appliqué sur la surface d'échantillon.
PCT/GB2012/000567 2011-07-08 2012-07-03 Tomographie en cohérence optique dans le domaine de fourier WO2013007967A1 (fr)

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GB201111743A GB201111743D0 (en) 2011-07-08 2011-07-08 Fourier domain OCT
GB1111743.9 2011-07-08

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040075844A1 (en) * 2002-07-01 2004-04-22 Marron Joseph C. Frequency-scanning interferometer with non-specular reference surface
US20070206197A1 (en) * 2005-11-15 2007-09-06 Bioptigen, Inc. Spectral Domain Phase Microscopy (SDPM) Dual Mode Imaging Systems And Related Methods And Computer Program Products
US7821643B2 (en) 2006-09-06 2010-10-26 Imalux Corporation Common path systems and methods for frequency domain and time domain optical coherence tomography using non-specular reference reflection and a delivering device for optical radiation with a partially optically transparent non-specular reference reflector

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040075844A1 (en) * 2002-07-01 2004-04-22 Marron Joseph C. Frequency-scanning interferometer with non-specular reference surface
US20070206197A1 (en) * 2005-11-15 2007-09-06 Bioptigen, Inc. Spectral Domain Phase Microscopy (SDPM) Dual Mode Imaging Systems And Related Methods And Computer Program Products
US7821643B2 (en) 2006-09-06 2010-10-26 Imalux Corporation Common path systems and methods for frequency domain and time domain optical coherence tomography using non-specular reference reflection and a delivering device for optical radiation with a partially optically transparent non-specular reference reflector

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
A. R. TURNTINSON; J. K. BARTON; B. POVAZAY; H. SATTMAN; A. UNTERHUBER; R. A. LEITGEB; W. DREXLER: "Endoscope-tip interferometer for ultrahigh resolution frequency domain optical coherence tomography in mouse colon", OPT. EXPRESS, vol. 14, 2006, pages 1878 - 1887
HOUSSINE MAKHLOUF ET AL: "Integrated fluorescence confocal and spectral-domain optical coherence tomography microendoscope", PROCEEDINGS OF SPIE, SPIE, US, vol. 7893, 1 January 2011 (2011-01-01), pages 789314 - 1, XP009162679, ISSN: 0277-786X *
MACIEJ WOJTKOWSKI; ANDRZEJ KOWALCZYK; TOMASZ BAJRASZEWSKI; RAINER LEITGEB; ADOLF F: "Fercher In vivo human retinal imaging by Fourier domain optical coherence tomography", J. BIOMED. OPT., vol. 7, 2002, pages 457
R. A. LEITGEB; M. WOJTKOWSKI: "Optical Coherence Tomography", 2008, SPRINGER, article "Complex and Coherence Noise Free Fourier Domain Optical Coherence Tomography", pages: 177 - 207

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