[go: up one dir, main page]

WO2018217171A1 - Appareil, sonde optique et procédé de caractérisation in vivo d'un tissu - Google Patents

Appareil, sonde optique et procédé de caractérisation in vivo d'un tissu Download PDF

Info

Publication number
WO2018217171A1
WO2018217171A1 PCT/SG2018/050256 SG2018050256W WO2018217171A1 WO 2018217171 A1 WO2018217171 A1 WO 2018217171A1 SG 2018050256 W SG2018050256 W SG 2018050256W WO 2018217171 A1 WO2018217171 A1 WO 2018217171A1
Authority
WO
WIPO (PCT)
Prior art keywords
oct
optical
signal
tissue
medium
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Ceased
Application number
PCT/SG2018/050256
Other languages
English (en)
Inventor
Zhiwei Huang
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
National University of Singapore
Original Assignee
National University of Singapore
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by National University of Singapore filed Critical National University of Singapore
Publication of WO2018217171A1 publication Critical patent/WO2018217171A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0075—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence by spectroscopy, i.e. measuring spectra, e.g. Raman spectroscopy, infrared absorption spectroscopy
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/45—For evaluating or diagnosing the musculoskeletal system or teeth
    • A61B5/4538—Evaluating a particular part of the muscoloskeletal system or a particular medical condition
    • A61B5/4542—Evaluating the mouth, e.g. the jaw
    • A61B5/4552—Evaluating soft tissue within the mouth, e.g. gums or tongue
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/48—Other medical applications
    • A61B5/4869—Determining body composition
    • 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
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0205—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows
    • G01J3/0208—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows using focussing or collimating elements, e.g. lenses or mirrors; performing aberration correction
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0205—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows
    • G01J3/0218—Optical elements not provided otherwise, e.g. optical manifolds, diffusers, windows using optical fibers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/02—Details
    • G01J3/0294—Multi-channel spectroscopy
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/2823—Imaging spectrometer
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01J—MEASUREMENT OF INTENSITY, VELOCITY, SPECTRAL CONTENT, POLARISATION, PHASE OR PULSE CHARACTERISTICS OF INFRARED, VISIBLE OR ULTRAVIOLET LIGHT; COLORIMETRY; RADIATION PYROMETRY
    • G01J3/00—Spectrometry; Spectrophotometry; Monochromators; Measuring colours
    • G01J3/28—Investigating the spectrum
    • G01J3/44—Raman spectrometry; Scattering spectrometry ; Fluorescence spectrometry
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00—Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02—Details of sensors specially adapted for in-vivo measurements
    • A61B2562/0233—Special features of optical sensors or probes classified in A61B5/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00—Measuring for diagnostic purposes; Identification of persons
    • A61B5/68—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient
    • A61B5/6801—Arrangements of detecting, measuring or recording means, e.g. sensors, in relation to patient specially adapted to be attached to or worn on the body surface
    • A61B5/6813—Specially adapted to be attached to a specific body part
    • A61B5/6814—Head
    • A61B5/682—Mouth, e.g., oral cavity; tongue; Lips; Teeth

Definitions

  • the present disclosure relates to an apparatus, optical probe and method for in vivo characterisation of a tissue; and in particular, using Raman spectroscopy (RS) and optical coherence tomography (OCT).
  • RS Raman spectroscopy
  • OCT optical coherence tomography
  • Oral and pharyngeal cancers are the sixth most common malignancies worldwide, with an annual incidence of around 275,000 and 130,300 cases respectively.
  • the incidence rates of oral cancer are -7.0% in males and -2.6% in females.
  • a patient at an advanced stage of an oral cancer typically only has 30% of a 5-year survival rate.
  • the survival rate can be improved by up to 80% to 90% if the oral cancer can be detected and diagnosed early for appropriate treatments.
  • detection of early lesions in the oral cavity has not increased during the last two decades.
  • a visual examination followed by a tissue biopsy and a pathological assessment is the current gold standard for diagnosing oral cancer. However, this procedure is invasive, painful and time consuming. It is also not suitable for screening high-risk patients with multiple suspicious lesions.
  • RS Raman spectroscopy
  • OCT optical coherence tomography
  • RS is capable of revealing constituent-specific (e.g. DNA, proteins, lipids, and water) biochemical/biomolecular information about tissues and cells, and in particular of probing biochemical and biomolecular structures and conformations associated with disease transformation.
  • OCT can be used to detect changes in tissue scattering and to provide 2D/3D images of tissue morphology at micron/submicron scales.
  • the biomedical applications using either RS or OCT have been intensively investigated for label-free "optical biopsies" of tissues in vivo. [0004] Given that RS and OCT provide different yet complementary information based on their different working mechanisms, these techniques have been investigated for pre-cancer and cancer diagnosis in the oral cavity.
  • aspects of the present application relate to hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) in vivo characterisation of a tissue such as an oral tissue of a human subject.
  • RS Raman spectroscopy
  • OCT optical coherence tomography
  • an optical probe for in vivo characterisation of a tissue comprising:
  • RS Raman spectroscopy
  • OCT optical coherence tomography
  • the described embodiment provides an optical probe for in vivo characterisation of a tissue.
  • the optical probe comprises a RS source input to provide a RS signal, an OCT source input to provide an OCT signal and an optical device configured to direct the RS and OCT signals to incident in vivo onto the tissue simultaneously (or at substantially the same time), the results of which (e.g. RS spectra and OCT images) provide a better understanding of the biochemical and morphological profiles of different tissues or regions such as in the oral cavity.
  • biochemical and morphological profiles of distinctive anatomical regions in the oral cavity can be highly functionally specialized and can exhibit significant variations in structural properties and cell types (e.g. tissue thickness, distinct epithelium types, vascularity, papillae, bone, etc.), understanding of the variations in the morphology and biochemistry of different oral tissue sites advantageously enhances oral tissue diagnosis and characterisation.
  • structural properties and cell types e.g. tissue thickness, distinct epithelium types, vascularity, papillae, bone, etc.
  • the optical probe allows transmission of both RS and OCT signals simultaneously, thereby reduces operating time in comparison to conventional methods of sequentially obtaining RS and OCT results.
  • the reduced operating time improves convenience and experience for patients undergoing examination using the hybrid RS and OCT method.
  • the RS and OCT signals provided by the optical probe are configured to incident on a same area of a tissue. This provides area specific information of the tissue in real time which may otherwise be difficult to achieve if the same area has to be located for measurements to be taken in sequence (i.e. the information from each method may not match exactly to the same area of interest if the RS and OCT measurements are to be taken sequentially).
  • the RS signal may be transmitted along a RS optical path having a RS optical axis, while the OCT signal may be transmitted along an OCT optical path having an OCT optical axis.
  • the OCT optical path may be arranged adjacent to the RS optical path with the OCT optical axis being parallel to the RS optical axis.
  • the optical device may be arranged to co-align the RS signal and the OCT signal to produce a co-aligned RS and OCT signal where the co-aligned RS and OCT signal is transmitted along a co- aligned optical axis which is orthogonal to the OCT optical axis to enable the co-aligned RS and OCT signal to be incident on the issue simultaneously.
  • the optical device may comprise an optical element arranged to receive the RS signal along the RS optical path and to deflect the RS signal to the co-aligned axis, and an OCT optical element configured to receive the OCT signal along the OCT optical path and to deflect the OCT signal to the co-aligned axis towards the optical element, where the optical element is transmissive to enable the OCT signal to pass through to be co-aligned with the RS signal.
  • the RS optical path may comprise:
  • a RS lens for focusing the RS signal towards the optical element; and a RS medium for directing the RS signal from the RS source input to the RS lens.
  • the RS lens may have a refractive index of 1.76.
  • the RS lens may include a plano-convex lens having a radius of curvature of 3mm.
  • the RS medium may include at least one Raman excitation fiber and at least one Raman collection fiber.
  • the OCT optical path may comprise an OCT medium for transmitting the OCT signal from the OCT source input to the optical element where the OCT medium has a proximal end and a distal end, and an OCT scanning mirror at the proximal end of the OCT medium for lateral scanning of the OCT signal.
  • the OCT medium may be a rod lens of half-pitch.
  • the OCT optical path may include a reflection rod mirror near the distal end of the OCT optical medium.
  • the optical device may include a focusing lens arranged to focus the co-aligned RS and OCT signal on the issue.
  • the optical element may include a dichroic mirror; such as a long-pass dichroic mirror.
  • the optical probe may comprise a handheld housing body for housing the optical device, the RS signal input and the OCT signal input, where the handheld body has a length of about 218 mm and a width of about 10 mm.
  • an apparatus for in vivo characterisation of a tissue comprising:
  • a Raman laser source for generating the RS signal and arranged to be coupled to the RS source input;
  • the apparatus may comprise a detector for receiving a plurality of resultant RS signals reflected from the tissue and a parabolic-aligned fiber arranged to compensate image aberration of the received resultant RS signals.
  • the detector may be arranged to receive a plurality of resultant OCT signals reflected from the tissue
  • the apparatus may comprise a reference OCT medium provided in a reference path of the OCT laser source where the reference OCT medium is identical to the OCT medium of the optical probe and is arranged to compensate for dispersion and optical delay of the resultant OCT signals caused by the OCT medium.
  • the reference OCT medium may be a rod lens of half-pitch.
  • the received plurality of resultant RS signals and plurality of resultant OCT signals may be processed to form combined data for determining abnormalities in the tissue.
  • the combined data may be processed using partial least squares (PLS)- discriminant analysis (DA) and leave-one-tissue site out, cross-validation (LOOCV) to determine the abnormalities of the tissue.
  • PLS partial least squares
  • DA discriminant analysis
  • LOOCV leave-one-tissue site out, cross-validation
  • the OCT laser source may be coupled to an optical coupler to produce first and second OCT optical outputs, the first OCT optical output including part of the laser source output for calibrating the OCT laser source.
  • the second OCT optical output may include part of the laser source output for directing into an interferometer for further splitting the second OCT optical output into a reference OCT signal for the reference OCT medium and the OCT signal for transmission to the OCT source input.
  • the characterised tissue may be used for demarcation of tumour resection margins of the tissue.
  • the tissue may be an oral tissue or other tissue of a human subject.
  • a method for in vivo characterisation of a tissue comprising:
  • RS Raman spectroscopy
  • OCT optical coherence tomography
  • the method may further comprise:
  • the method may further comprise:
  • the optical element being transmissive to enable the OCT signal to pass through for co-alignment with the deflected RS signal.
  • the method may further comprise providing a RS lens along the RS optical path, focusing the RS signal, by the RS lens, towards the optical element; and directing the RS signal from the RS source input to the RS lens.
  • the method may further comprise providing an OCT medium along the OCT optical path, transmitting the OCT signal from the OCT source input to the optical element, the OCT medium having a proximal end and a distal end, and may comprise lateral scanning of the OCT signal at the proximal end of the OCT medium.
  • the method may further comprise generating the RS signal by a RS laser source and transmitting the RS signal to the RS source input, and generating the OCT signal by an OCT laser source and transmitting the OCT signal to the OCT source input.
  • the method may further comprise detecting a plurality of resultant RS signals reflected from the tissue, and compensating image aberration of the received resultant RS signals using a parabolic-aligned fiber.
  • the method may further comprise detecting a plurality of resultant OCT signals reflected from the tissue, providing a reference OCT medium in a reference path of the OCT laser source where the reference OCT medium is identical to the OCT medium, and may comprise compensating for dispersion and optical delay of the resultant OCT signals caused by the OCT medium.
  • the method may further comprise processing the detected plurality of RS signals and the OCT signals to form combined data for determining abnormalities of the tissue.
  • the method may further comprise processing the combined data using partial least squares (PLS)- discriminant analysis (DA) and leave-one-tissue site out, cross- validation (LOOCV) to determine the abnormalities of the tissue.
  • PLS partial least squares
  • DA discriminant analysis
  • LOOCV leave-one-tissue site out
  • LOCV cross- validation
  • the OCT laser source may be coupled to an optical coupler to produce first and second OCT optical outputs, the first OCT optical output including part of the laser source output; and the method may comprise calibrating the OCT laser source based on the first OCT optical output.
  • the method may further comprise directing the second OCT optical output into an interferometer where the second OCT optical output includes part of the laser source output and the method may comprise further splitting the second OCT optical output into a reference OCT signal for the reference OCT medium and the OCT signal for transmission to the OCT source input.
  • Embodiments therefore provide an apparatus, optical probe and method for in vivo characterisation of a tissue that allows transmission of both RS and OCT signals simultaneously. This advantageously reduces operating time in comparison to conventional methods of sequentially obtaining RS and OCT results.
  • the optical probe may comprise a handheld housing body suitably sized to direct the RS and OCT signals particularly onto oral tissues in an oral cavity of a human subject.
  • Figure 1A shows a schematic of a hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) apparatus for in vivo characterisation of a tissue, with the apparatus comprising a RS laser source, an OCT laser source and an optical probe according to an embodiment;
  • RS Raman spectroscopy
  • OCT optical coherence tomography
  • Figure 1 B shows a schematic of the RS laser source of Figure 1 A
  • Figure 1 C shows a schematic of the OCT laser source of Figure 1A
  • Figure 2A is a schematic diagram of the optical probe of Figure 1A;
  • Figure 2B is an exemplary photograph of the optical probe of Figure 2A;
  • Figures 3A and 3B illustrate using the optical probe of Figure 2B to access an oral cavity for in vivo characterisation of oral tissues, with Figure 3A illustrating the optical probe being placed at a buccal region of the oral cavity and Figure 3B illustrating the optical probe being used for characterisation of a ventral tongue surface in the oral cavity;
  • Figure 4 shows in vivo OCT images of an oral cavity obtained using the optical probe of Figure 1A.
  • FIG. 4 shows OCT images take from (i) a hard palate; (ii) a soft palate; (iii) a floor; (iv) a buccal region; (v) a ventral tongue surface; (vi) a lip; (vii) a dorsal tongue surface; and (viii) a tooth in the oral cavity;
  • Figure 5 shows in vivo fingerprint and high-wavenumber (FP/HW) Raman spectra acquired in real-time under OCT imaging guidance using the optical probe of Figure 1A;
  • Figure 6 shows in vivo OCT images of an oral cavity obtained using the optical probe of Figure 1A, and specifically, Figures 6(i) to (vi) show OCT images taken from (i) a left side of an alveolar process; (ii) a right side of the alveolar process; (iii) a left side of a lateral tongue; (iv) a right side of the lateral tongue; (v) a left side of a floor
  • Figure 8 shows calculated results of a difference between in vivo FP/HW
  • Figure 9 shows representative attenuation coefficients distribution derived from the OCT images of Figure 6, and specifically, Figures 9(i) to (vi) show representative attenuation coefficients distribution for (i) a left side of an alveolar process; (ii) a right side of the alveolar process; (iii) a left side of a lateral tongue; (iv) a right side of the lateral tongue; (v) a left side of a floor of a mouth; and (vi) a right side of the floor of a mouth;
  • Figure 10 shows a bar histogram ⁇ 1 SD of the relative frequency of various attenuation coefficients for an alveolar process, a lateral tongue and a floor of a mouth using the results obtained in Figure 9;
  • Figure 1 1 shows a one-way analysis of variance (ANOVA) of an alveolar process, a lateral tongue and a floor of a mouth over an entire FP/HW Raman spectral range (i.e. 800-1800 cm “1 , and 2800-3600 cm “1 ) using the Raman spectra of Figure 7; and
  • ANOVA analysis of variance
  • Figure 12 shows a bar histogram ⁇ 1 SD of statistically different Raman peaks for an alveolar process, a lateral tongue and a floor of a mouth (i.e. 853 cm “1 , 960 cm “1 , 1078 cm “1 , 1265 cm “1 , 1302 cm “1 , 1445 cm “1 , 1655 cm “1 , 2850 cm “1 , 2885 cm “1 , 2940 cm “1 , 3250 cm “1 , and 3400 cm “1 ) using the Raman spectra of Figure 7.
  • ⁇ 1 SD of statistically different Raman peaks for an alveolar process, a lateral tongue and a floor of a mouth
  • FIG. 1A shows a schematic of a hybrid Raman spectroscopy (RS) and optical coherence tomography (OCT) apparatus 100 for in vivo characterisation of a tissue 108 in accordance with an embodiment.
  • the apparatus 100 comprises a RS system 102 for generating a RS signal and an OCT imaging system 104 for generating an OCT signal.
  • the RS system 102 and the OCT imaging system 104 are operatively connected to a respective RS source input 106a and a respective OCT source input 106b of an optical probe 106 arranged to direct the RS signal and the OCT signal to the tissue 108.
  • the optical probe 106 is arranged to direct the RS and OCT signals to be incident on the tissue 108 simultaneously, and this advantageously reduces an operating time in comparison to conventional methods of sequentially obtaining RS and OCT results from the tissue 108.
  • the optical probe 106 includes a handheld body, as illustrated in Figure 2B, for ease of handling so that the optical probe 106 may be used to reach specific areas of a human subject, such as to characterise an oral tissue of a human subject.
  • the apparatus 100 comprises a detector (not shown in Figure 1A) for receiving a plurality of resultant RS signals and a plurality of resultant OCT signals reflected from the tissue 108, where the plurality of resultant RS signals and the plurality of resultant OCT signals received are processed to form combined data for determining abnormality in the tissue 108.
  • the RS system 102 is in the form of a simultaneous fingerprint (FP, 800-1800 cm “1 ) and high-wavenumber (HW, 2800-3600 cm “1 ) Raman spectroscopy system, which is capable of acquiring in vivo tissue Raman spectra within 0.5 s by using the optical probe 106.
  • the fiber-optic FP/HW RS system developed for real-time in vivo tissue Raman measurements consists of a RS laser source 110 in the form of a 785 nm diode laser (maximum output: 300 mW, B&W TEK Inc.) for generating the RS signal, a high-throughput reflective imaging spectrograph 1 12 (Acton LS-785 f/2, Princeton Instruments Inc.) equipped with a customized 830 gr/mm gold-coated grating that has a -85% diffraction efficiency in the NIR range of 800-1200 nm.
  • the detector of the apparatus 100 comprises a RS camera 1 14 for receiving a plurality of resultant RS signals from the tissue 108.
  • the RS camera 1 14 is a thermo electric- coo led (-70 °C), NIR-optimized deep-depletion charge-coupled device (CCD) camera (PIXIS 400BR-eXcelon, Princeton Instruments Inc.) configured to collect the plurality of resultant RS signals and resides within the RS system 102.
  • the incident power on a surface of the tissue 108 for Raman measurements is ⁇ 10 - 15 mW.
  • the OCT imaging system 104 is in the form of a swept-source optical coherence tomography (SS-OCT) imaging system with a frequency swept laser source (SL1325-P16, Thorlabs) as an OCT laser source 120 for generating the OCT signal.
  • the OCT imaging system 104 is configured to transmit at least one OCT signal and to receive a plurality of resultant OCT signals.
  • An output of the laser source 120 of the OCT imaging system e.g.
  • the fiber coupler 122 (or generally an optical coupler) is arranged to produce a first OCT optical output (the 20% portion) for calibrating of the OCT laser source 120, and a second OCT optical output (the 80% portion) for directing into the interferometer 126.
  • the interferometer 126 further splits the second OCT optical output into a reference arm 130 and a sample arm 132 using a broadband 50/50 coupler 128 (FC1310-70-50-APC, Thorlabs). Specifically, the second OCT optical output is split into a reference OCT signal for the reference arm 130, and the OCT signal for the sample arm 132.
  • the imaging speed of the OCT imaging system 104 is 25 frames per second (512 x 512 pixels).
  • a further OCT medium is provided in the reference arm 130 of the OCT system 104.
  • the further OCT medium is identical to the OCT medium and is arranged to compensate for dispersion and optical delay of the OCT signal caused by the OCT medium.
  • the further OCT medium is a second identical half-pitch GRIN rod lens.
  • the measured axial and lateral resolutions of the OCT imaging system 104 coupled with the GRIN rod lens are 12 ⁇ in air (9 ⁇ in tissue) and 12 ⁇ respectively.
  • the tissue interrogation depth of the OCT imaging system 104 is 1.8 mm.
  • the sensitivity of the OCT imaging system 104 coupled with the RS-OCT optical probe 106 developed with a silver mirror (PF10-03-P01 , Thorlabs Inc.) placed at the focal plane of the GRIN rod lens (i.e. the OCT medium) at its distal end together with a neutral density filter (NDF) (NDL-25C-4, Thorlabs Inc.) is measured with an attenuation of -50 dB.
  • NDF neutral density filter
  • SNR signal-to-noise ratio
  • FIG. 2A shows a schematic 200 of the optical probe 106 developed for in vivo tissue measurements of Figure 1A.
  • the optical probe 106 comprises a Raman sampling arm 202 for transmission of the RS signal along a RS optical path having a RS optical axis 204, and an OCT sampling arm 206 for transmission of the OCT signal along an OCT optical path having an OCT optical axis 208.
  • the optical probe 106 further includes an optical device 201 for directing the RS and OCT signals to be incident on the tissue 108.
  • the optical device 201 is arranged to co-align the RS signal and the OCT signal to produce co-aligned RS and OCT signals (or a co- aligned RS and OCT signal) which are then transmitted along a co-aligned optical axis 210 which is orthogonal to the OCT optical axis 208 to enable the co-aligned RS and OCT signals to be incident on the tissue 108 simultaneously.
  • the optical device 201 includes an optical element in the form of a dichroic mirror 212 and the RS and OCT signals transmitted via the sampling arms 202, 206 are co-aligned by the dichroic mirror 212 to be incident on the tissue 108 via a focusing lens in the form of a glass window 214.
  • the dichroic mirror 212 is a customized 5 mm x 7 mm long pass dichroic mirror 212 (LPDM) (DMLP 1180, Thorlabs). Instead of a long pass dichroic mirror 212, it should be appreciated that the mirror may also be a short-pass dichroic mirror.
  • LPDM 5 mm x 7 mm long pass dichroic mirror 212
  • the mirror may also be a short-pass dichroic mirror.
  • the RS optical path of the Raman sampling arm 202 includes a fiber optic RS medium 216 coupled with a RS converging lens 218 (L1) for directing the RS signal to the dichroic mirror 212 and to the glass window 214.
  • the path of the RS signal comprises (i) transmission 220 via the fiber-optic RS medium 212, (ii) focusing 222 by the converging RS lens 208, and (iii) deflection 224 by the dichroic mirror 212.
  • the RS medium 216 is configured to at least transmit the RS signal from the RS source input 106a to the dichroic mirror 212 and is made up of a 1.8 mm fiber-optic.
  • the RS medium 216 comprises at least one Raman excitation fiber 226 (E) and at least one Raman collection fiber 228 (C).
  • the RS lens 218 of this embodiment is a specially designed converging lens with a refractive index of 1.76 configured to focus the RS signal to the dichroic mirror 212.
  • the RS lens 218 comprises a 3.8 mm thick flat window of sapphire (4.8 mm in diameter) and a distal plano-convex sapphire lens which has a radius of curvature of 3 mm.
  • the RS lens 218 is configured to enable a focal distance of ⁇ 6 mm from the RS lens 218 to a surface of the tissue 108, and a beam size of ⁇ 360 ⁇ .
  • the RS signal is deflected by the dichroic mirror 212 to the co- aligned axis 210 which is substantially orthogonal to the RS optical axis 204 (i.e. at an angle of 90°, although it may not be strictly 90°) to the co-aligned axis 210.
  • the RS signal (and the OCT signal) is then transmitted onto the surface of the tissue 108 through the glass window 214. Monte Carlo simulations indicate that -80% of the Raman signal collected arises from the top -300 ⁇ layer along the central axis of the OCT image (see e.g.
  • Figure 2A with a lateral range of -360 ⁇ in diameter on a surface of the tissue 108 and an estimated tissue probing volume of -0.019 mm 3 , making it well suited for superficial tissue Raman measurements which yield complementary biochemical and biomolecular constituents of the tissue with respect to OCT imaging.
  • the OCT path of the OCT sampling arm 206 includes an OCT medium 230 and an OCT mirror 232 for directing the OCT signal to the dichroic mirror 212 and to the glass window 214.
  • the OCT medium 230 is configured to transmit the OCT signal from the OCT source input 106b from a proximal end of the OCT medium 230 to a distal end of the OCT medium 230.
  • the OCT medium 230 is a half-pitch gradient index (GRIN) rod lens (Gradient Lens Corporation) such that the OCT signal at the distal end of the GRIN rod lens 230 is the same as that of its proximal end.
  • GRIN half-pitch gradient index
  • the diameter of the GRIN rod lens 230 is 4.6 mm, which ensures a lateral scanning range of 4.6 mm of the OCT signal. This advantageously provides a relatively large field of view for investigating microstructural features of the tissue 108.
  • the OCT mirror 232 is configured to deflect the OCT signal and is a reflection rod mirror (M1 : 54-098, Edmund Optics).
  • the OCT signal formed by an achromatic objective lens is relayed (illustrated by arrow 234) from the proximal end of the OCT medium 230 to its distal end, deflected 236 by the reflection rod mirror 232 (M1), and subsequently incident onto a surface of the tissue 108 after passing through the transmissive dichroic mirror 212 (LPDM) and the glass window 214.
  • the optical probe 106 is configured to direct the OCT signal through the dichroic mirror 212 to enable the RS and the OCT signals to be co-aligned and incident onto the tissue 108 simultaneously.
  • the OCT signal is deflected by the OCT mirror 232 at an orthogonal angle to direct the OCT signal to the dichroic mirror 212 although the angle may not be strictly 90° and other angles may be possible as long as the OCT signals are aligned with the RS signals to enable the OCT and the RS signals to be incident onto the tissue 108 simultaneously.
  • the optical probe 106 is therefore configured to co-align the RS and OCT signals along the co-aligned axis 210 by using the dichroic mirror (LPDM) 212 which is configured to allow the OCT signal to transmit through while deflecting the Raman signal to enable a co-alignment of the RS and OCT signals along the co- aligned axis 210 to enable the co-aligned RS and OCT signals to incident simultaneously on the tissue 108.
  • the apparatus 100 comprises at least one OCT scanning mirror provided at the proximal end of the OCT medium 230 to enable lateral scanning of the OCT signal on the tissue 108.
  • the at least one OCT scanning mirror comprises XY galvo scanning mirrors located at the proximal side of the OCT medium 218 (e.g. at a back-focal plane of an OCT objective in the OCT imaging system 104).
  • the at least one OCT scanning mirror is located at the OCT imaging system 104.
  • FIG. 2B shows an image of the optical probe 106 of Figure 2A.
  • the optical probe 106 includes a handheld housing body 222 for housing the various components of the optical probe 106 and the dimension of the housing body 222 is -120 mm in length with a head size 222 of ⁇ 13 mm x 8 mm, making it suitable to be handheld and/or for in vivo tissue measurements on human organs, such as the oral cavity, cervix, and skin, or for intraoperative monitoring (e.g., brain operation).
  • the optical probe 106 comprises an aperture 224 at a side of the optical probe 106 where the co-aligned RS and the OCT signals exits and incident onto the tissue 108 simultaneously.
  • the optical probe 106 may therefore be considered as a side-viewed optical probe 106 since the RS and OCT signals are 'bent' orthogonally to be co-aligned.
  • the handheld optical probe 106 developed enables simultaneous acquisition of tissue FP/HW Raman spectra and OCT images in vivo from the tissue 108.
  • the optical probe 106 may be used in characterisation of oral tissues (i.e. alveolar process, lateral tongue, and floor of the mouth, accounting for 80% of all cases of OCSCC) in the oral cavity.
  • Figures 3A and 3B illustrate using the optical probe 106 of Figure 2B to access an oral cavity for in vivo characterisation of oral tissues.
  • Figure 3A illustrates characterisation of a buccal region of the oral cavity of a human subject
  • Figure 3B illustrates characterisation of a ventral tongue surface in the oral cavity of the human subject.
  • Both oral tissue biochemical and morphological information can be harvested in vivo in real-time by using the handheld optical probe 106.
  • Figure 4 shows in vivo OCT images of an oral cavity as obtained from the optical probe 106 of Figure 1A. More specifically, (i) to (viii) of Figure 4 show OCT images take from (i) a hard palate; (ii) a soft palate; (iii) a floor; (iv) a buccal region; (v) a ventral tongue surface; (vi) a lip; (vii) a dorsal tongue surface; and (viii) a tooth in an oral cavity of the healthy human subject.
  • the scale bars in the horizontal and vertical directions of the OCT images as shown in Figure 4 are 1 mm and 400 ⁇ respectively.
  • Figure 5 shows in vivo fingerprint and high-wavenumber (FP/HW) Raman spectra derived from the apparatus 100 of Figure 1A.
  • the corresponding in vivo FP/HW Raman spectra from the oral cavity are acquired in real-time under OCT imaging guidance of Figures 4(i) - 4(viii).
  • Results of the OCT images obtained in Figure 4 will be discussed in conjunction with the FP/HW Raman spectra acquired in Figure 5 below to illustrate the utility of the RS-OCT optical probe 106 coupled with the FP/HW RS system 102 and SS-OCT system 104 for real-time in vivo Raman measurements of epithelial tissues under OCT imaging guidance.
  • FIG. 4(i) an OCT image of a masticatory mucosa (i.e. a hard palate mucosa) of the oral cavity is shown.
  • the corresponding FP/HW Raman spectrum of the hard palate is shown in Figure 5.
  • the hard palate exhibits intense FP/HW Raman signals mainly associated with bone minerals (i.e. phosphate stretching vibration at 959 cm -1 of hydroxyapatite), indicating a dense collagen fibrous attachment of mucosa to an underlying bone structure of the hard palate. This can be compared with observations in the hard palate OCT imaging (see e.g.
  • Figure 4(i) which reveals strong and interlaced bundles of collagen fibers and thereby confirming the existence of these dense collagen fibers in the hard palate.
  • OCT imaging identifies a -150 ⁇ thick epithelium layer (EL) overlying a -200 ⁇ lamina intestinal (LP) with a clear boundary. This is consistent with histopathology reports.
  • the results of Figure 4(i) and Figure 5 demonstrate that complementary tissue biochemical and morphological information can be harvested in vivo in real-time by using the hybrid RS-OCT technique (e.g. using the apparatus 100 and the optical probe 106 for hybrid RS and OCT measurements/characterisation).
  • FIG. 4(H) to 4(v) display OCT images acquired from the soft palate, the floor of the mouth, the buccal and the ventral surface of the tongue, respectively.
  • the soft-palate is characterized by a non-keratinized epithelium (EL) (-330 ⁇ ) shown as a transparent strip on top of a laminar muscular (LP) in Figure 4(H).
  • EL non-keratinized epithelium
  • FIG. 4(iii) shows a clear contrast between a superficial epithelium layer (EL) and a lamina intestinal (LP) of the floor of the mouth.
  • the OCT image of the buccal is shown in Figure 4(iv).
  • a non-keratinized epithelium (EL) of the buccal with a thickness of approximately 200 to 350 ⁇ is identified on top of a lamina intestinal (LP) of the buccal.
  • a cluster of connective tissue layers within -600 ⁇ depth of the laminalitis (LP) are also found.
  • the epithelium (EL) thickness of the ventral surface of the tongue changes from a slightly thinner epithelium (EL) (-140 ⁇ ) on the right side of the OCT image to a thicker epithelium (EL) (-230 ⁇ ) on the left side.
  • the lamina intestinal (LP) of the ventral tongue is characterized by a rich blood supply and fiber-rich regions, leading to a high reflection from dispersed locations along the lamina intestinal (LP).
  • the relative smaller thickness of the ventral tongue epithelium (EL) (-140 - 230 ⁇ ) and the laminalitis (LP) ( ⁇ 230 ⁇ ) makes the submucosa (SM) visible in the OCT image of the ventral tongue.
  • the blood vessels (BV) are shown as darker regions in OCT images due to high absorption coefficients of hemoglobin in the vessels.
  • the OCT images ( Figures 4(H) - 4(v)) recorded using the optical probe 106 are in good agreement with the histology images of the oral cavity, casting light on the structures of the lining mucosa of the oral cavity.
  • the FP/HW Raman spectra acquired offer exclusive insights of the biochemical components in the oral cavity.
  • Raman peak intensity ratio calculations can be used to quantify the FP/HW Raman spectra difference observed.
  • the protein to lipid Raman peak ratio i.e., /2940 /2850
  • gradually increases mouth floor: 0.96, soft palate: 1.10, ventral tongue: 1.70, and buccal: 1.88 in the oral lining mucosa, signifying various different protein and lipid contents of the different tissue sites in the oral lining mucosa.
  • the gradually increasing protein-to-lipid Raman peak ratio for the oral lining mucosa can be explained by an increase in the collagen content and a relatively decreased oleic acid content (the ratios of collagen to oleic acid contribution are: 1.24 (mouth floor), 1.65 (soft palate), 1.68 (ventral tongue), and 1.93 (buccal)).
  • the ratios of collagen to oleic acid contribution are: 1.24 (mouth floor), 1.65 (soft palate), 1.68 (ventral tongue), and 1.93 (buccal)).
  • different water contents are found as indicated by the varying ratios of the Raman peaking at 3250 cm “1 and 3400 cm “1 (mouth floor: 0.80, soft palate: 1.01 , ventral tongue: 1.06, and buccal: 1.16), which is likely to be caused by differences in local structures of hydrogen-bonded networks in the epithelium of the lining mucosa.
  • FIG. 4(vii) shows a mucosa of the dorsum of the tongue with a clear separation between an epithelium (EL) and an underlying lamina propria (LP).
  • the dorsal tongue has no submucosa (SM) but is directly attached to the muscular body of the tongue.
  • Filiform lingual papillae (FLP) are also identified in the OCT image of Figure 4(vii). While the OCT images show clear contrast between different parts of the specialized oral mucosa, the FP/HW RS is capable of revealing the corresponding biochemical constituents as shown in Figure 5.
  • the OCT imaging shows the blood vessels (BV) within the lamina propria (LP) of the lip (see e.g. Figure 4(vi)), while the Raman spectrum sheds light on the lip component at the molecular level as indicated by a Raman peak at 1579 cm -1 which signifies a presence of hemoglobin (see e.g. Figure 5).
  • FIG. 4(viii) shows an OCT image of a front tooth which is scanned perpendicular to a dorsal facial surface of the front tooth by using the optical probe 106.
  • the tooth OCT image reflects a morphology and structure of a human tooth, showing a clearly visible facial enamel (E), dentin (D), and dentil-enamel junction (DEJ).
  • the thickness of the tooth enamel (E) can be obtained from the OCT image, which is measured at -1000 ⁇ and is similar to previous reports.
  • the FP/HW Raman spectrum of the tooth can also be acquired along a central axis of the tooth (representative of a central axis shown in the tooth OCT image), providing complementary information on the biochemical constituents of the tooth.
  • a central axis of the tooth depictative of a central axis shown in the tooth OCT image
  • presence of a prominent tooth Raman peak at 959 cm “1 (v s (P-0) of hydroxyapatite) indicates hydroxyapatite as a main component of the tooth.
  • a broad Raman spectral band of water OH stretching vibrations peaking at -3250 and -3400 cm -1 ) is also observed in the Raman spectrum of the tooth.
  • tissue optical properties e.g. a total attenuation coefficient
  • tissue biochemical information obtained from FP/HW Raman spectra among different oral tissues can be performed using the hybrid RS- OCT apparatus 100 of Figure 1A. This is discussed in more detail below. This advantageously enhances in vivo tissue diagnosis and characterisation of the oral cavity.
  • Tissue FP/HW Raman spectra and OCT images were simultaneously acquired in vivo from clinically relevant anatomical locations of oral tissues (i.e. alveolar process, lateral tongue, and floor of the mouth, accounting for 80% of all cases of OSCC) in an oral cavity of a human subject.
  • oral tissues i.e. alveolar process, lateral tongue, and floor of the mouth, accounting for 80% of all cases of OSCC
  • a total of 26 normal healthy human subjects (8 females and 18 males, mean average ages of 32) were recruited for in vivo Raman-OCT measurements of their oral cavities. Exclusion criteria include smokers, regular alcohol consumers and subjects suffering from systemic or oral mucosal diseases.
  • all subjects underwent extensive mouthwash to reduce confounding factors (e.g. food debris, microbial coatings etc.).
  • a total of 6 anatomic locations i.e. left and right sides of an alveolar process: left and right sides of a lateral tongue; left and right sides of a floor of a mouth
  • the inter-anatomical morphological and biochemical variations of different normal tissues in the oral cavity were assessed using the hybrid RS-OCT technique.
  • the one-way analysis of variance (ANOVA) with Fisher post hoc least significant difference (LSD) analysis was used to elucidate the statistically different Raman-active components among the different sites (i.e. the alveolar process, the lateral tongue and the floor of the mouth) in the oral cavity.
  • Partial least squares (PLS)- discriminant analysis (DA) and leave one- tissue site out, cross-validation (LOOCV) were applied on both the Raman spectra and the OCT images obtained using the hybrid RS-OCT technique to classify the different sites of the oral cavity.
  • PLS Partial least squares
  • DA discriminant analysis
  • LOOCV cross-validation
  • the multivariate statistical analysis was performed using in-house written scripts in the Matlab programming environment (Mathworks, Inc., Natick, MA).
  • Figure 6 shows in vivo OCT images of an oral cavity obtained using the optical probe 106 of Figure 1A. More specifically, (i) to (vi) of Figure 6 show representative OCT images taken from (i) a left side of an alveolar process; (ii) a right side of the alveolar process; (iii) a left side of a lateral tongue; (iv) a right side of the lateral tongue; (v) a left side of a floor of a mouth; and (vi) a right side of the floor of a mouth.
  • the morphology of the different tissue sites exhibits significant differences (e.g. thickness variability, distinct epithelia types, muscularity, vascularity, bone etc.).
  • SD standard deviation
  • Figure 8 shows calculated results of a difference between the in vivo FP/HW Raman spectra in Figure 7 (i.e. (i) lateral tongue - floor of mouth; (ii) alveolar process - floor of mouth; and (iii) alveolar process - lateral tongue) ⁇ 1 SD (shaded area).
  • the difference Raman spectra i.e. lateral tongue - floor of mouth, alveolar process - floor of mouth, and alveolar process - lateral tongue
  • a hierarchical clustering dendrogram analysis (data not shown) performed based on the FP/HW spectra of the alveolar process (left and right sides), the lateral tongue (left and right side), the floor of the mouth (left and right sides) shows that the alveolar process, the lateral tongue and the floor of the mouth can be generally clustered into 3 distinct groupings, with no significant differences found between the left and right sides of the same anatomical locations.
  • Figure 9 shows representative attenuation coefficients distribution derived from the OCT images of Figure 6. More specifically, Figures 9(i) to 9(vi) show representative attenuation coefficients distribution for (i) the left side of the alveolar process; (ii) the right side of the alveolar process; (iii) the left side of the lateral tongue; (iv) the right side of the lateral tongue; (v) the left side of the floor of the mouth; and (vi) the right side of the floor of the mouth.
  • the optical attenuation coefficients associated with different tissue morphologies can be derived from the OCT images of Figure 6 using the equation below: where ⁇ ( ⁇ ) is the depth-dependent optical attenuation coefficient; /(z) is the intensity of the OCT image recorded, and D is the OCT imaging depth.
  • ⁇ ( ⁇ ) is the depth-dependent optical attenuation coefficient
  • /(z) is the intensity of the OCT image recorded
  • D is the OCT imaging depth.
  • the total RS-OCT dataset acquired is randomly split into 2 parts: that is, 80% of the total dataset is used for training (838 in vivo Raman spectra and OCT images: 264 for the alveolar process; 271 for the lateral tongue; and 303 for the floor of the mouth) from 21 normal human subjects; while the remaining 20% of the total RS-OCT dataset is used for predictive testing (211 in vivo Raman spectra and OCT images: 67 for the alveolar process; 68 for the lateral tongue; and 76 for the floor of the mouth) from 5 normal human subjects.
  • Figure 10 shows a bar histogram ⁇ 1 SD of the relative frequency of various attenuation coefficients for the alveolar process, the lateral tongue and the floor of the mouth using the results obtained in Figure 9.
  • the histogram distributions of optical attenuation coefficients corresponding to the Raman sampling areas are intriguingly different for the different tissue sites.
  • Results of PLSDA and LOOCV implemented on the attenuation coefficients histogram ( Figure 10) are shown in Table 1 below.
  • OCT Training Data Set OCT Testing Data Set (20% of (80% of total dataset) total dataset
  • Table 1 Confusion matrix detailing the multiclass classification results of OCT attenuation coefficients for different oral tissues using the PLS-DA with leave-one tissue site-out, cross- validation methodology.
  • Table 1 shows that the 3 tissue sites can generally be well separated with varying sensitivities (the alveolar process: 75.0%, the lateral tongue: 78.2%, the floor of the mouth: 47.2%), and specificities (the alveolar process: 96.2%, the lateral tongue: 67.7%, the floor of the mouth: 85.0%). Further implementation of the OCT diagnostic models developed on the testing dataset gives predictive sensitivities (the alveolar process: 86.6%, the lateral tongue: 67.6%, the floor of the mouth: 47.4%), and specificities (the alveolar process: 95.8%, the lateral tongue: 70.6%, the floor of mouth: 83.0%), indicating the inter-anatomical morphological differences of the oral cavity.
  • Figure 11 shows a one-way analysis of variance (ANOVA) of the alveolar process, the lateral tongue and the floor of the mouth over an entire FP/HW Raman spectral range (i.e. 800-1800 cm “1 , and 2800-3600 cm “1 ) using the Raman spectra of Figure 7.
  • ANOVA one-way analysis of variance
  • LSD least significant difference
  • Figure 12 displays a histogram of statistically different Raman peak intensities (mean ⁇ 1SD) from both the FP and the HW ranges at 853 cm “1 , 960 cm “1 , 1078 cm “1 , 1265 cm “1 , 1302 cm “1 , 1445 cm “1 , 1655 cm “1 , 2850 cm “1 , 2885 cm “1 , 2940 cm “1 , 3250 cm “1 and 3400 cm “1 , confirming the capability of the hybrid RS-OCT technique to reveal different biochemical and biomolecule constituents (e.g. proteins, lipids, DNA and water) for the different locations of the oral cavity in vivo.
  • the difference spectra ⁇ 1 SD in Figure 8 and the ANOVA analysis in Figure 11 resolve the inter-anatomical biochemical variability, suggesting that different oral tissue sites exhibit unique Raman spectral profiles.
  • Table 2 shows that the FP/HW Raman spectra could differentiate the alveolar process, the lateral tongue and the floor of the mouth with sensitivities of 90.2%, 77.5%, 48.8%, and specificities of 95.8%, 72.1 %, 88.8%, respectively.
  • the Raman diagnostic model developed on the training dataset was implemented, showing that the alveolar process, the lateral tongue and the floor of the mouth could be differentiated with sensitivities of 89.6%, 72.1 %, 51.3%, and specificities of 93.8%, 74.8%, 86.7%, respectively.
  • the analysis results of FP/HW Raman spectra ( Figure 7) reveal the inter-anatomical biochemical differences among the different oral tissues in vivo.
  • Table 3 Confusion matrix detailing the multiclass classification results of the integrated Raman spectroscopy and OCT attenuation coefficients for different oral tissues using the PLS-DA with leave-one tissue site-out, cross-validation methodology [0080]
  • the results in Table 3 show that the alveolar process, the lateral tongue and the floor of the mouth could be differentiated with sensitivities of 99.6%, 82.3%, 50.2%, and specificities 97.0%, 75.1 %, 92.1 %, respectively using the hybrid RS-OCT technique implemented on the training dataset.
  • the alveolar process shows a significantly (P ⁇ .0001 ) intensive Raman peak at 960 cm -1 (v s (P— O) of hydroxyapatite) than either the lateral tongue or the floor of the mouth (see e.g. Figure 12), signifying that the alveolar process is mainly characterized by the bone minerals.
  • the observation of the intensive bone Raman peak is also consistent with the OCT images of the alveolar process which reveals the bone structure below the top gingival (see e.g. Figures 6(i) and 6(H)).
  • the OCT images reveals that the alveolar process mainly comprises the top gingival and the underlying bone structure (see e.g.
  • lipids content in addition, relative contributions by the lipids content to the Raman spectra of the lateral tongue and the floor of the mouth are much higher than that of the alveolar process as indicated by a significantly reduced Raman peak at 1078 cm -1 (v(C— C) of lipids) (see e.g. Figure 12).
  • the lowest lipids content associated with the alveolar process is possibly a result of the alveolar process being mainly consists of the collagen-rich gingiva and the underlying bone enriched with bone minerals.
  • the abundant phospholipids contained within the superficial layers of the lateral tongue and the floor of the mouth account for their significantly boosted lipid Raman intensities as compared to the alveolar process.
  • the increased protein content of the alveolar process can be explained by its high keratin content within the top gingiva.
  • the HW Raman spectra shows a gradually reduced protein content along with a significantly increased lipid content for the tissue sites across the alveolar process, the lateral tongue and the floor of mouth. This observation is in good agreement with the observation of the FP range as discussed above.
  • the significantly reduced water contribution to the Raman spectra was found in the lateral tongue and the floor of the mouth (see e.g. Figure 12). This is possibly due to the increased lipid content of the lateral tongue and the mouth floor which reduces their water permeability. Their reduced water content is reflected by the reduced Raman peaks at 3250 and 3400 cm -1 assigned to the OH stretching vibrations as shown in Figure 12.
  • the alveolar process, the lateral tongue and the floor of the mouth could be differentiated using the hybrid RS-OCT technique (see e.g. Tables 1 - 3).
  • the enhanced clustering accuracy using the hybrid RS-OCT technique can be explained by its capability to simultaneously uncover both the rich biochemical and biomolecular information (i.e. proteins, lipids, DNA and water content, etc.) with FP/HW RS and complementary tissue morphology information (e.g. attenuation coefficients) represented by the OCT imaging technique.
  • the alveolar process is classified with a significantly higher sensitivity than other anatomical locations, signifying that the alveolar process has a unique morphology (see e.g. Figures 6 to 8) and molecular profile (see e.g. Figures 9 to 12) compared to the lateral tongue and the floor of the mouth.
  • the results obtained using the optical probe 106 for in vivo characterisation of oral tissues indicate that biochemical and morphological variations of different oral tissue sites should be taken into account for development of accurate tissue diagnosis and characterisation in the oral cavity.
  • Combining the spatially co- registered tissue Raman spectra and optical attenuation coefficients acquired with the hybrid RS-OCT technique, better differentiation (e.g. higher sensitivity and specificity) among different anatomical tissue locations in the oral cavity can be provided as compared to using the RS or the OCT technique alone.
  • the optical probe 106 is a clinically useful tool for enhancing real-time in vivo detection and diagnosis of oral disease (e.g. pre-cancer and/or early cancer) or a tissue abnormality in the oral cavity.
  • oral disease e.g. pre-cancer and/or early cancer
  • the hybrid RS-OCT technique can be used to differentiate oral malignant lesions from normal tissue as well as for determining/demarcating tumour margins for/during surgical operations in the oral cavity.
  • Other multivariate algorithms e.g. support vector machine
  • can also be applied to integrate the biochemical and morphological/vascular information e.g.
  • the vascularity acquired with Doppler OCT and so on harvested using the hybrid RS-OCT technique for further enhanced detection of oral malignancies (e.g. oral cancer of epithelial origin, salivary gland tumours, tumour vascularity).
  • oral malignancies e.g. oral cancer of epithelial origin, salivary gland tumours, tumour vascularity.
  • the in vivo RS-OCT measurements may also be applied to a series of head and neck patients to evaluate the clinical merits of the optical probe 106 for improving in vivo diagnosis and characterisation of early cancer in the oral cavity in clinical settings.

Landscapes

  • Physics & Mathematics (AREA)
  • Health & Medical Sciences (AREA)
  • Spectroscopy & Molecular Physics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Physics & Mathematics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Public Health (AREA)
  • Biomedical Technology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Biophysics (AREA)
  • Engineering & Computer Science (AREA)
  • Veterinary Medicine (AREA)
  • Radiology & Medical Imaging (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Dentistry (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Investigating, Analyzing Materials By Fluorescence Or Luminescence (AREA)
  • Investigating Or Analysing Materials By Optical Means (AREA)

Abstract

L'invention concerne une sonde optique à main et un procédé de caractérisation in vivo d'un tissu. La sonde optique comprend une entrée de source de spectroscopie Raman (RS) agencée pour fournir un signal RS; une source d'entrée de tomographie par cohérence optique (OCT) conçue pour fournir un signal OCT; et un dispositif optique conçu pour co-aligner le signal RS et le signal OCT pour qu'ils frappent simultanément le tissu.
PCT/SG2018/050256 2017-05-25 2018-05-24 Appareil, sonde optique et procédé de caractérisation in vivo d'un tissu Ceased WO2018217171A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
SG10201704278V 2017-05-25
SG10201704278V 2017-05-25

Publications (1)

Publication Number Publication Date
WO2018217171A1 true WO2018217171A1 (fr) 2018-11-29

Family

ID=64396907

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/SG2018/050256 Ceased WO2018217171A1 (fr) 2017-05-25 2018-05-24 Appareil, sonde optique et procédé de caractérisation in vivo d'un tissu

Country Status (1)

Country Link
WO (1) WO2018217171A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114795120A (zh) * 2021-11-22 2022-07-29 北京航空航天大学 一种多模态成像装置

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040260183A1 (en) * 2003-02-05 2004-12-23 Lambert James L. Non-invasive in vivo measurement of macular carotenoids
US20090021724A1 (en) * 2007-07-20 2009-01-22 Vanderbilt University Combined raman spectroscopy-optical coherence tomography (rs-oct) system and applications of the same
EP2913663A1 (fr) * 2014-02-28 2015-09-02 IMEC vzw Spectromètre optique à portée adaptée
CN105406333A (zh) * 2015-12-23 2016-03-16 长春理工大学 基于ASE泵浦的1.7μm波段可调谐拉曼光纤激光器

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20040260183A1 (en) * 2003-02-05 2004-12-23 Lambert James L. Non-invasive in vivo measurement of macular carotenoids
US20090021724A1 (en) * 2007-07-20 2009-01-22 Vanderbilt University Combined raman spectroscopy-optical coherence tomography (rs-oct) system and applications of the same
EP2913663A1 (fr) * 2014-02-28 2015-09-02 IMEC vzw Spectromètre optique à portée adaptée
CN105406333A (zh) * 2015-12-23 2016-03-16 长春理工大学 基于ASE泵浦的1.7μm波段可调谐拉曼光纤激光器

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
EGODAGE K. D. ET AL.: "The combination of optical coherence tomography and Raman spectroscopy for tissue characterization", J. OF BIOMEDICAL PHOTONICS & ENG, vol. 1, no. 2, 30 June 2015 (2015-06-30), pages 169 - 177, XP055562850, [retrieved on 20180817] *
VARKENTIN A. ET AL.: "Trimodal system for in vivo skin cancer screening with combined optical coherence tomography-Raman and colocalized optoacoustic measurements", J. BIOPHOTONICS, vol. 11, no. 6, 26 February 2018 (2018-02-26), pages 1 - 12, XP055562855, [retrieved on 20180817] *
WANG J. ET AL.: "Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique", J BIOPHOTONICS, vol. 11, 2 November 2017 (2017-11-02), pages 1 - 9, XP055562851, [retrieved on 20180817] *
WANG J. ET AL.: "Development of a hybrid Raman spectroscopy and optical coherence tomography technique for real-time in vivo tissue measurements", OPT. LETT., vol. 41, no. 13, 27 June 2016 (2016-06-27), pages 3045 - 3048, XP055562848, [retrieved on 20180817] *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN114795120A (zh) * 2021-11-22 2022-07-29 北京航空航天大学 一种多模态成像装置
WO2023088110A1 (fr) * 2021-11-22 2023-05-25 北京航空航天大学 Appareil d'imagerie multimodale
US12343110B2 (en) 2021-11-22 2025-07-01 Beihang University Multi-modal imaging device

Similar Documents

Publication Publication Date Title
KR102053483B1 (ko) 라만 분광법에 관한 진단 기기 및 방법
Amelink et al. Non-invasive measurement of the morphology and physiology of oral mucosa by use of optical spectroscopy
Krafft et al. Biomedical applications of Raman and infrared spectroscopy to diagnose tissues
CN105190262B (zh) 诊断仪器和方法
US11419499B2 (en) Optical coherence tomography for cancer screening and triage
JP6230077B2 (ja) 光ファイバーラマン分光法を利用する内視鏡検査でのリアルタイム癌診断に関連する方法
JP4870356B2 (ja) 組織を測定するための高波数ラマン分光法の使用
US20070167836A1 (en) Multi modal spectroscopy
WO2013160780A1 (fr) Technique d'imagerie et de spectroscopie infrarouge à ondes courtes pour la classification d'inflammations et la différentiation des tumeurs et des inflammations dans des tissus humains à l'intérieur du corps
US20090326359A1 (en) Method of in vivo detection and/or diagnosis of cancer using fluorescence based dna image cytometry
US20240377627A1 (en) Method and apparatus for quantitative hyperspectral fluorescence and reflectance imaging for surgical guidance
Krafft et al. Diagnosis and screening of cancer tissues by fiber-optic probe Raman spectroscopy
Wang et al. Characterizing biochemical and morphological variations of clinically relevant anatomical locations of oral tissue in vivo with hybrid Raman spectroscopy and optical coherence tomography technique
Bratchenko et al. In vivo hyperspectral imaging of skin malignant and benign tumors in visible spectrum
WO2018217171A1 (fr) Appareil, sonde optique et procédé de caractérisation in vivo d'un tissu
RU2528087C1 (ru) Устройство для определения концентрации гемоглобина и степени оксигенации крови в слизистых оболочках
Zakharov et al. Combined autofluorescence and Raman spectroscopy method for skin tumor detection in visible and near infrared regions
Bratchenko et al. In vivo hyperspectral analysis of skin hemoglobin and melanin content for neoplasia detection
TWI588492B (zh) 陣列式近場光學高散射材料檢測方法
Borisova et al. Multispectral autofluorescence diagnosis of non-melanoma cutaneous tumors
Yu et al. Fiber optic Raman spectroscopy for in vivo detection of nonmuscle invasive bladder cancer at cystoscopy
Gambino et al. Ex vivo microstructural investigations of oral lichen planus lesions by spectral domain optical coherence tomography
Patil et al. Raman Spectroscopy: From Benchtop to Bedside
Chen et al. Real-time delineation of basement membrane in human oral and esophageal mucosa with micro-optical coherence tomography
Taroni et al. Time Domain Multi-Wavelength Diffuse Optics for Breast Cancer Management

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 18805084

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

122 Ep: pct application non-entry in european phase

Ref document number: 18805084

Country of ref document: EP

Kind code of ref document: A1