WO2020130969A1

WO2020130969A1 - A laser diffuse optical tomography device used in back projection geometry

Info

Publication number: WO2020130969A1
Application number: PCT/TR2019/050485
Authority: WO
Inventors: Murat Canpolat
Original assignee: Akdeniz Universitesi
Priority date: 2018-12-21
Filing date: 2019-06-21
Publication date: 2020-06-25
Also published as: EP3897361A1; EP3897361A4; TR201820052A1

Abstract

The invention relates to a laser diffuse optical tomography (LDOT) device that is used in back reflection geometry, that has been developed to detect and locate tissue mass and tumours. The inventive optical device involves multiple fiber optic cables directing lasers to the relevant tissue from the laser source; the laser scatters with diffusion and the laser reflecting of the surface is collected by multiple detector fibers which are measured by photodiodes. The measured light intensity is used in a reconstruction algorithm and the tomographical image of the relevant area of the tissue is formed based on blood spatial distribution. The inventive device is especially used for the diagnosis of breast tumours.

Description

A LASER DIFFUSE OPTICAL TOMOGRAPHY DEVICE

USED IN BACK PROJECTION GEOMETRY

TECHNICAL FIELD

PRIOR ART

Tomographic images are three dimensional (3D), and they are used to obtain information about the inner structures of objects. In the case of the laser breast diffuse optical tomography (LBDOT) device, near infrared light with a wave length of 700-900 nm is used, and a tomographic image is formed with the LMDOT device by two different methods. The first involves light intensities that are sent from multiple sources to the turbid environment, that are collected and measured by multiple detectors after they pass through the turbid environment (US 6738658B2) . The light intensities that pass through the turbid environment are measured by way of photodiodes or charge coupled devices (CCD) . A 3D image is formed with the results of the measurements by way of algorithms such as "back projection", "algebraic reconstruction technique", or "least square method". The second method involves the laser sent from multiple sources directed towards the turbid environment reflecting from the surface after being diffused. The returning laser is collected by multiple detector optic fibers and the intensities are measured by photodiodes. (US201110091064A1 ) .

With diffuse optical tomography (DOT) devices, light is sent via multiple sources, and multiple detectors measure the intensity. As the light sending efficiency of each source and the light collection efficiency of each detector is not the same, source and detector calibration must be carried out. All light intensities must be equalised in the source calibration. The light collection efficiency is equalised during the detector calibration. Therefore, the measurements are independent of the device and only dependant on the turbid environment's properties. In the calibrations developed for DOT devices utilised in back reflection geometry, the calibration values of the source and detector are entered into the reconstruction algorithms as a parameter and calculated (WO 01/192241 Al) .

The invention in question describes a laser diffuse optical tomography device for the diagnosis of breast tumours.

BRIEF DESCRIPTION AND PURPOSES OF THE INVENTION

The present invention is a laser diffuse optical tomography device used in back reflection geometry; its purpose is to form an image of the relevant area, in which a tumour diagnosis is to be made, with an area of 5x5 cm2, and a depth of 2.5-3 cm, and therefore, effectively diagnose the tumour and determine its location . Due to the fact that the number of source-detector pairs is high (2500), the 3D images formed by way of reconstruction algorithms has a high spatial resolution.

The inventive device is compact, easy to use, and does not discomfort the patient while in use.

BRIEF DESCRIPTION OF THE FIGURES Figure 1. Image of the LMDOT device while in use.

Figure 2. Schematic image of the LMDOT device.

Figure 3. Open design of the LMDOT device.

Figure 4. Detailed view of the optic switch of the LMDOT device.

Figure 5. Image of the main electronic card and the aluminium block over the detector.

Figure 6. Image of the end of the optic fibers used as detectors in the grooves on the aluminium block and the main electronic card .

Figure 7. Image of the front face of the optic probe and the array of fiber optic cables.

Figure 8. Image of the array of source fibers on the front face of the optic probe used as the source, and the detector fibers used as the detector

Figure 9. Image of the laser sent from the source optic fibers to the tissue and the returning laser, and the representations of photon orbits within the tissue. REFERENCE NUMBERS GIVEN IN THE FIGURES

10) Laser diffuse optical tomography (LDOT) device

20) Optic probe

21) Optic probe front face

22) Source optic fiber front face

23) Detector optic fiber front face 30) Tissue

40) Optic switch step motor

50) Fiber optic cable

51) Fiber optic cable connecting the laser to the device

52) Source optic fiber

53) Detector optic fiber

60) Aluminium block

61) Optic switch

70) Main electronic card

71) Integrated circuit

72) Microprocessor

80) Aluminium block over the detector

81) Groove

90) Photodiode

91) Power source of the motherboard

92) Output of the motherboard that controls the step motor and optic selector

93) Connecting cable

94) Computer 95) Computer monitor

100) Representations of photon orbits within the tissue

101) Laser sent to the tissue

102) Laser returning from the tissue 110) Laser source

DETAILED DESCRIPTION OF THE DEVICE

This invention relates to an optical device that enables the determination of whether a mass, in a patient with a mass, is a tumour, a cyst or a hamartoma, and the determination of the location of the mass/tumour. The inventive optical device, is essentially a laser diffuse optic tomography (LDOT) device (10) that has been developed to determine whether a mass in a patient with a mass, is a tumour, a cyst or a hamartoma, and to determine the location of the tumour.

The laser diffuse optic tomography (LDOT) device (10), is used by gently touching the device to the tissue in which there is the possibility of the existence of a mass. The operation method of the laser diffuse optic tomography (LDOT) device (10) on the tissue (30) is illustrated in Figure 1. The LDOT device (10), touches the tissue (30) by way of an optic probe (20) . As illustrated in Figure 2, the inventive LDOT device (10) comprises a diode laser source (110), an optic probe (20) that enables the contact between the tissue (30) and the LDOT device (10), fiber optic cables (50) on the front face of the probe (21) that conduct the laser to the optic probe (20) and that collect the returning laser from the tissue (30), the main electronic card (70), an optic switch (61), an optic switch step motor (40), the aluminium block (60) housing the optic switch (61), the integrated circuit (71), the microprocessor (72), photodiodes (90), a computer (94), a connection cable, and a computer monitor. The output of the motherboard that controls the step motor and optic switch (92) conveys the information that conducts the laser to the source optic fibers (52) for specific periods of time, from the motherboard (70) to the step motor (40) .

During the measurement conducted for the purpose of diagnosis, the optic probe front face (21) of the laser diffuse optic tomography (LDOT) device (10) is fully in contact with the tissue (30) . The connected fiber optic cables (50) are located on the front face of the optic probe (21) . One end of the fiber optic cables (50) is connected to the optic probe (201), and the other is connected to the aluminium block (80) and the optic switch on the detector. Some of the aforementioned fiber optic cables (50) are detector optic fibers (53) and are located in the grooves (81) on the aluminium block (80) . The photodiodes (90) are placed inside the grooves (81) on the aluminium block (80) . Therefore, the light carried by each detector optic fiber (53) is conducted to a single photodiode (90) . While at least a single fiber optic cable (50) enters one end of the grooves (81), the other end of the grooves (81) are connected to the photodiodes (90) located on the electronic card (70) illustrated in Figure 5 with a lock- key relationship. Due to the connection of the grooves (81) and the photodiodes (90), the connection of the optic probe (20) and the main electronic card (70) is enabled by way of detector fiber optics (53) . The main electronic card (70), as illustrated in Figure 4, is located under the aluminium block (80) on which the electronic components are located.

The front face of the optic probe (21) of the optic probe (20) has been illustrated in Figure 7. Fiber optic cables (50) are located in the front surface of the optic probe (21) . Some of the fiber optic cables (50) located on the front face of the optic probe (21) convey the laser to the tissue (30), and the rest collect the laser that is returning from the tissue (30) after having been diffused, and conveys it to the photodiodes (90) that are located on the main electronic card (70) and that are used as sensors. Of the aforementioned fiber optic cables (50), the ones that convey the laser to the optic probe (20) are source optic fibers (52), and the ones that collect the returning laser and convey it to the photodiodes (90) are detector optic fibers (53) .

As seen in the general view of the LDOT device (10) in Figure 1, the laser is conducted from the laser source to the source optic fiber (52) located on the optic switch and the optic probe (20) by way of the fiber optic cable (51) . The laser (101) conveyed to the tissue (30) by way of the source optic fibers (52) is diffused in the tissue (30) .

As shown in Figure 5, one end of the detector optic fibers (53) that collects the light returning from the tissue (30) and conducts it to the photodiodes (90) is attached to the grooves (81) in the aluminium block (80) above the detector. In the inventive device, the photodiodes (90) that are used as sensors on the main electronic card (70) are placed in the grooves (81) (Figure 6) . The photodiode (90) outputs are conducted to at least one DDC232 integrated circuit on the main electronic card (70) . There, the data is made digital and the photodiode (90) currents are turned into voltage at different integration times and transferred to a computer (94) as output.

The source optic fibers (52) conveying the laser to the optic probe (20), and the detector optic fibers (53) that collect the light returning from the tissue (30) and convey it to the photodiodes (90) are located on a matrix on the optic probe front face (21) . The diameters of the fiber optic cables (50) used in the optic probe (20) are 1-3 mm and the centre to centre distance between the closest source-detector pairs is 1-10. The locations of the source fibers (22) and the detector fibers (23) are visible on the optic probe front face (21) . The source optic fiber (52) connected to the optic probe front face (22) of the optic probe (20) ends at the source optic probe front face (22) . Likewise, the detector optic fibers (53) end at the detector optic fiber front face (23) . Therefore, the contact between the tissue (30) and the detector optic fibers (53) that collect the back reflecting light from the tissue (30) and conveys it to the photodiodes (90), is established while the source optic fibers (52) on the front face of the optic probe (21) convey the light to the optic probe (20) .

Figure 9 schematically illustrates the representative photon orbits within the tissue of the laser (101) that is conveyed to the tissue (30) by way of the source optic fibers (52), and the laser (102) that is returning after diffusion in the tissue (30), and illustrates an example of five separate detector optic fibers (53) collecting them. This illustration is only a representation, and the number of source optic fibers (52) and detector optic fibers (53) may change and the representative photon orbits within the tissue may increase or decrease accordingly .

In the structural representation illustrated in Figure 9, when the laser (101) conveyed to the tissue is selected as a source; while the depth to which the laser (102) returning from the tissue that is collected by the detectors is swallow, as the source-detector distance increases, the penetration depth of the laser orbits within the tissue (30) increases. The depth to which the laser (102) returning from the tissue that is collected by detectors close to the source is always smaller than the depth to which the laser (102) returning from the tissue that is collected by detectors far from the source.

In the inventive LDOT device (10); lasers are conveyed to the tissue (30) from multiple sources, and the laser is diffused within the tissue (30), and the back projecting laser is collected by multiple detector optic fibers and the intensity is measured by way of photodiodes (90) . The measured light intensities are used in a reconstruction algorithm and a 3D tomographic image is formed that determines the location of the tumour or mass.

The working principle of the inventive developed LDOT device (10) comprises the following steps;

- Directing a laser by a diode laser source (110) to the optic switch (61) by way of a fiber optic cable (51),

- Conveying the laser by way of the fiber optic cable (51) to the source optic fibers (52) and the optic switch (61) in order, that are attached to the laser source (110) and that convey the laser to the device, and conveying the laser to different locations on the object and the optic probe front face (21) and the source optic probe front face (22),

- Conveying the laser to subject that is to be diagnosed for mass/tumours by way of the source optic fibers (52) that end at the optic probe front face (21) at the source fibers (22) ,

- Collecting the laser that is back reflected by the subject that is to be diagnosed for mass/tumours after it is received by the detector optic fibers (53) located in the detector fibers (23) on the optic probe front face (21), - conveying the optic fibers (53) to the main electronic card (70) that carries photodiodes (90),

- converting the photodiode (90) current outputs into voltage at different integration times by at least one integrated circuit, and transmitting to a computer (94),

- carrying out the source-detector calibration of the measurements taken from the subject by dividing them with the result of the measurement taken in a homogenous turbid environment ,

- using "simultaneous iterative reconstruction technique (SIRT)", "truncated conjugate gradient (CG) " or "truncated singular value decomposition (TSVD)" methods to form a 3D image of the part of the subject that is under the optic probe (20) and determining the mass/tumour and its location,

The subject mentioned in the inventive method is a tissue, especially a breast.

By way of calibration method of the LDOT device (10) operation method, the light sending and collecting efficiencies of the sources and the detectors are normalised by way of the calibration method, the measurement values are made to be independent of the distance between the source and detector. Calibrated data aroused as perturbation data in reconstruction algorithms to create 3D images. An optically homogenous environment is taken as a reference and the 3D image is formed depending on the blood dispersal within the tissue by way of the perturbation values of the measurements taken from the tissue being calculated.

While the LDOT device (10) is working, as a laser is conveyed from each source optic fiber (52) to the tissue (30), the detector optic fibers (53) collect the back reflecting laser after it has been diffused within the tissue (30) and convey it to the photodiodes (90) . The photodiode (90) outputs on the LDOT device's (10) main electronic card (70) are conducted to at least two analogue digital converter DDC232 integrated circuits (71) on the main electronic card (70) . Switches, integral acceptor circuits, analogue digital converters (preferably 20 bits) and triggering devices are located on the DDC232 integrated circuits (71) . Within the DDC232 integrated circuit (71), there are 2 integral acceptor circuits for each photodiode. These integral acceptor circuits are current voltage converters that can operate continuously. The integration time varies between 1-900 ms. Different integration time is used for each detector. Data logging and the control of DDC232 integrated circuits (71) is carried out on a microprocessor (72) . For source-detector pairs that are close neighbours a short integration time in which the measured values are not saturated is used, whereas for distant source-detector pairs long integration time is used to be able to receive a high enough signal. Therefore, the dynamic data gathering space of the system is increased. Table 2 contains the circuit card current/power measurement values.

Table 2. Circuit card current/power measurement

* The circuit supply voltage for the measurements in Table is

12.02 V.

Calibration of the device

A measurement is taken in a homogenous turbid environment for calibration purposes, M_cai . The measurement of the breast, M_breast/ is divided by the measurement taken in the homogenous turbid environment and calibration is made for each source-detector pair (R M_breast/M_cai) .

For the formation of a tomographic image from the calibrated breast measurements, reconstruction techniques are used. For this technique the perturbation data of each of the source- detector pairs needs to be calculated. The perturbation data is the difference between the measurement taken from the breast in the presence of a tumour and the measurement taken from the breast when there is no tumour. As to consecutive measurements cannot be taken from the breast in this way, perturbation must be approximately calculated in a different way. In the aforementioned invention, the calibration data is used directly as perturbation values. These values give the optical change in a homogenous environment of the breast containing tumour. The obtained perturbation data are used in the y = Ax E? (1)

equation obtained by way of the Rytov approach from the diffusion equation, y is the perturbation data in Mxl format and M is the total number of measurements. A is the weight matrix and its dimension is MxN. N, is the is the voxel number within the volume that is being imaged. The x in the equation is the difference between the attenuation coefficient of the voxel and the background and its dimension is Nxl .

Equation 1, in open format is expressed as such:

In this context, 6y(r_si, r_d2) is the perturbation measurement that forms due to the absorption of the laser that is sent from the first source and collected by the second detector, in the tissue (30) . wi,2_;i, in the second column of the middle matrix, is the coefficient value of the first voxel value of the weight matrix of the laser that is sent from the primary source and collected by the secondary detector and 6p_a(r2) is the difference of absorption coefficient depending on the background of the voxel in the position of, r2. An optically homogenous opaque environment with the values of p_a and m₃ ' is used in background calibration. . The weight matrix in Equation 2 is obtained by the linearization of the diffusion equation by way of the Rytov approach. The wavelength of the laser source (110) that is used is 810 nm, and the absorption of light at this wavelength by Intralipid and water is low, while its absorption by blood is high. Due to the increase in blood build-up in areas with tumours, the absorption of light increases and the intensities measured by photodiodes (90) decreases. The solution of Equation 2gives the differences in the absorption coefficients of each voxel, which is the 6 _a(r) values. To this end, "simultaneous iterative reconstruction technique (SIRT)", "truncated conjugate gradient (CG) " and "truncated singular value decomposition (TSVD)" methods are used to form a three dimensional (3D) image of the area of the breast under the probe, and the location of the tumour is determined.

Due to the fact that the distance between the source/detectors on the optic probe (20) on the inventive LMDOT device (10), being 0.5- 7 cm, the spatial distribution of the blood in the tissue to a depth of 2.5- 3 cm as of the surface of the breast is observable .

Claims

1. A laser diffuse optic tomography (LDOT) device (10) operating in back reflection geometry for the purpose of the diagnosis and location of tissue (30) tumours characterised by; comprising a diode laser source (110) for conveying light to the tissue, an optic probe enabling the contact between the tissue (30) and the LDOT device (10), fiber optic cables (50) located on the front face of the probe (21) that convey the laser to the optic probe (20) and collect the laser back reflection from the tissue (30), a main electronic card (70) that controls the optic switch (61) carrying an integrated circuit (71), an optic switch that conveys the optic fiber cable (51) connected to the diode laser source (110), to the optic fiber cables (52) used as the source in order, an optic switch step motor (40), an aluminium block (60) that houses the optic switch (61), at least one integrated circuit (71) that converts the photodiode (90) current to voltage for different integration intervals and that contains an analogue digital converter, a microprocessor (73) that controls the integrated circuit (71) and that enables the connection between the electronic motherboard (70) and the computer (94), photodiodes (90) that measure the intensity of the light and that are used as sensors, a computer (94), a connecting cable, and a computer monitor.

2 . Laser diffuse optic tomography device (10) of Claim 1, characterised in that; the detector fiber optic cables (53) are located in the grooves (81) in the aluminium block (80) .

3 . Laser diffuse optic tomography device (10) of Claim 1, characterised in that; some of the fiber optic cables (50) are source optic cables (52) that convey the laser to the optic probe (20) .

4 . Laser diffuse optic tomography device (10) of Claim 1, characterised in that; some of the fiber optic cables (50) are detector fiber optic cables (53) that are used as a sensor by collecting the laser that is back reflecting after diffusion in the tissue (30), and conveying it to the photodiodes (90) on the main electronic card (70) .

5 . Laser diffuse optic tomography device (10) of Claim 4, characterised in that; the detector optic fibers have ends that are attached to the grooves (81) in the aluminium block (80) above the photodiodes.

6. Laser diffuse optic tomography device (10) of Claim 1, characterised by; comprising photodiodes (90) on the main electronic card (70), that are used as sensors.

7 . Laser diffuse optic tomography device (10) of Claim 6, characterised in that; the photodiodes (90) are located in grooves (81) .

8. Laser diffuse optic tomography device (10) of Claim 1, characterised by; comprising at least one DDC232 integrated circuit (71) on the main electronic card (70) .

9 . Operation method of laser diffuse optic tomography device (10) of Claim 1, characterised by; comprising the process steps of,

- directing emission of a diode laser source (110) to the optic switch (61) by way of a fiber optic cable (51),

- conveying the laser by way of the fiber optic cable

(51) to the source optic fibers (52) and the optic switch (61) in order, that are attached to the laser source (110) and that convey the laser to the device, and conveying the laser to different locations on the object and the optic probe front face (21) and the source optic probe front face (22) , - conveying the laser to subject that is to be diagnosed for mass/tumours by way of the source optic fibers (52) that end at the optic probe front face (21) at the source fibers (22 ) ,

- collecting the diffused back reflected laser from the subject that is to be diagnosed for mass/tumours by the detector optic fibers (53) located in the detector fibers (23) on the optic probe front face (21),

- conveying the optic fibers (53) to the main electronic card (70) that carries photodiodes (90),

- carrying out the source-detector calibration of the measurements taken from the subject by dividing them with the result of the measurement taken in a homogenous turbid environment,

- using "simultaneous iterative reconstruction technique (SIRT)", "truncated conjugate gradient (CG) " or "truncated singular value decomposition (TSVD)" methods to form a 3D image of the part of the subject that is under the optic probe (20) and determining the mass/tumour and its location.

10. Operation method of Claim 9, characterised in that; the subject is a tissue.

11. Operation method of Claim 10, characterised in that; the tissue is a breast.

12. Operation method of Claim 9, characterised by; the normalisation of the light sending and collecting efficiencies of the sources and detectors with the applied calibration method.

13. Operation method of Claim 9, characterised in that; the measured values are made independent of variances in the source-detector distances by way of the applied calibration method .

14. Operation method of Claim 9, characterised in that; the data that have been calibrated are used as perturbation data in reconstruction algorithms to create 3D images.

15. Operation method of Claim 9, characterised by; an optically homogenous environment is taken as a reference and the 3D image is formed depending on the blood spatial distribution within the breast by way of the perturbation values of the measurements taken from the tissue being calculated.