Optical tissue phantom and method of forming the same

Abstract

An optical tissue phantom (OTP) is provided, comprising: a matrix comprising a hot melt adhesive; and a light scattering agent and a light absorbing agent dispersed in the matrix. A method of forming the OTP is also provided.

Description

Technical Field

[0001] This invention relates to an optical tissue phantom and a method for forming the same. Background Technology

[0002] Optical tissue phantoms (OTPs) play a crucial role in diagnosing various pathological conditions and in testing, calibrating, and validating medical imaging instruments and image reconstruction algorithms. Conventional OTPs are prone to degradation and loss of optical properties over time, and once fabricated, they are not easily adjustable. Previous techniques for forming OTPs were slow, taking more than a day and requiring numerous steps.

[0003] Therefore, there is a need for an improved optical tissue phantom and its formation method. Summary of the Invention

[0004] The present invention seeks to solve these problems and / or provide an improved optical tissue phantom and a method for forming the same.

[0005] According to a first aspect, an optical tissue phantom (OTP) is provided, the optical tissue phantom (OTP) comprising:

[0006] - A matrix containing hot melt adhesive; and

[0007] - Light scattering agents and light absorbers dispersed in the matrix.

[0008] The light scattering agent may include metal oxides, polymers, or combinations thereof. The light absorbing agent may include ink, toner, toner, or combinations thereof.

[0009] According to one particular aspect, the OTP may contain 0.1-0.5% (w / v) of the light-scattering agent.

[0010] According to one particular aspect, the OTP may contain 0.001-0.004% (v / v) of the light absorber.

[0011] According to one specific aspect, the scattering coefficient (μs') of the OTP at 850 nm can be 10-20 cm⁻¹. -1 The scattering coefficient (μs') of the OTP at 808 nm can be 12-18 cm⁻¹. -1 .

[0012] According to one specific aspect, the absorption coefficient (μa) of the OTP at 850 nm can be 0.02-0.08 cm⁻¹. -1 The absorption coefficient (μa) of the OTP at 808 nm can be 0.01-0.07 cm⁻¹.-1 .

[0013] According to a second aspect, a method for forming an optical tissue phantom (OTP) is provided, the OTP comprising: a matrix containing a hot-melt adhesive and a light scattering agent and a light absorbing agent dispersed in the matrix, the method comprising:

[0014] - Mix hot melt adhesive, light scattering agent and light absorber to form a mixture;

[0015] - Heat the mixture for a predetermined period of time;

[0016] - Repeat the mixing and heating process; and

[0017] - After the repetition, the mixture is cooled to form the OTP.

[0018] According to one particular aspect, the method may include melting the hot melt adhesive prior to the mixing.

[0019] Depending on a specific aspect, the repetition may be more than once.

[0020] According to one particular aspect, the mixing may include vacuum mixing.

[0021] According to one specific aspect, the mixing may include premixing the light scattering agent and the light absorbing agent. The premixing may include dispersing the light scattering agent and the light absorbing agent in water to form a dispersion. The method may include drying the dispersion.

[0022] According to one specific aspect, the heating can be carried out at a temperature of 120-210°C.

[0023] According to one specific aspect, the predetermined time period can be 15-30 minutes.

[0024] According to one specific aspect, the cooling can be carried out at a temperature of 20-30°C. Attached Figure Description

[0025] To enable a full understanding and easy implementation of the invention, exemplary embodiments will now be described by way of non-limiting examples, with reference to the accompanying illustrative drawings. In the drawings:

[0026] Figure 1 A schematic diagram of the general steps for making an optical tissue phantom is shown;

[0027] Figure 2 shows the measured optical parameters of optical tissue phantoms with different amounts of TiO2; Figure 2(a) shows the time-point spread function (TPSF) measured by time-domain near-infrared spectroscopy (TD-NIRS) (wavelengths = 808 nm and 850 nm, SD = 2.5 cm); Figure 2(b) shows the scattering coefficient (μs'); and

[0028] Figure 3 shows the optical parameters of optical tissue phantoms with different amounts of ink; Figure 3(a) shows the time point spread function (TPSF) measured by time-domain near-infrared spectroscopy (TD-NIRS) (wavelengths = 808 nm and 850 nm, SD = 2.5 cm); Figure 3(b) shows the absorption coefficient (μa). Detailed Implementation

[0029] As explained above, there is a need for an improved optical tissue phantom and a method for its formation.

[0030] In summary, the present invention provides an optical tissue phantom (OTP) and a method for forming the same. This OTP advantageously exhibits improved uniformity, resulting in reduced incident light scattering and increased accuracy and reliability in use. The method advantageously includes simple steps and is faster than conventional methods, providing controllable, repeatable, and accurate performance in the formed OTP, as well as a simple and low-cost fabrication process. Furthermore, the shape of the OTP can be easily formed and reformed, for example, using a mold. The OTP can be easily melted and reformed to have different properties simply by adjusting the proportions of the components.

[0031] According to a first aspect, an optical tissue phantom (OTP) is provided, the optical tissue phantom (OTP) comprising:

[0032] - A matrix containing hot melt adhesive; and

[0033] - Light scattering agents and light absorbers dispersed in the matrix.

[0034] In this disclosure, unless otherwise expressly stated, the use of the singular form includes the plural form. It should be noted that, as used in the specification and appended claims, the singular forms “a,” “an,” and “the” include the plural referent unless the context clearly specifies otherwise. Furthermore, the terms “including,” “comprising,” and “having,” as well as other forms such as “include,” “comprise,” and “have,” are not considered limiting.

[0035] In this disclosure, hot melt adhesives are defined as adhesives that become soft, moldable, or molten liquid at high temperatures and solidify upon cooling. Hot melt adhesives may be transparent.

[0036] In this disclosure, the term "light scattering agent" refers to any material capable of causing a deviation in the light path. In this disclosure, the term "light absorbing agent" refers to any material capable of absorbing radiant energy from light. In this disclosure, the term "light" refers to electromagnetic radiation of any wavelength.

[0037] The matrix may also contain any additives suitable for extending shelf stability and improving optical transparency and mechanical properties, including but not limited to fillers, stabilizers, etc.

[0038] Hot melt adhesives can be in the form of rods, pellets, or combinations thereof. Advantageously, hot melt adhesives maintain high stability after melting, cooling, and hardening, and are also non-toxic, thus environmentally friendly. Hot melt adhesives can include ethylene-vinyl acetate (EVA) copolymers, ethylene-acrylate copolymers, polyolefins, polyamides, styrene block copolymers, polycarbonates, or combinations thereof. Specifically, hot melt adhesives can include ethylene-vinyl acetate (EVA) copolymers. EVA copolymers advantageously have low absorption and scattering properties, thus making them suitable for OTP matrices with adjustable optical properties. They also maintain high stability after cooling and hardening, allowing for convenient long-term storage and transportation.

[0039] EVA copolymers can have any suitable ratio of ethylene to vinyl acetate. For example, EVA copolymers can contain 10-70% (w / w) vinyl acetate.

[0040] According to one specific aspect, light scattering agents may include metal oxides, polymers, or combinations thereof. Specifically, light scattering agents may include titanium dioxide, aluminum oxide, barium oxide, polystyrene, or combinations thereof. Light scattering agents may be in any suitable form, including but not limited to powders, microparticles, or combinations thereof.

[0041] According to one specific aspect, a light absorber may include ink, toner, toner, or a combination thereof. For example, a light absorber may be a particulate ink absorber, a molecular ink absorber, or a combination thereof. Ink may be a gel, sol, or solution containing at least one colorant. Ink may contain dyes, pigments, or a combination thereof.

[0042] Depending on one specific aspect, an OTP may contain 0.1-0.5% (w / v) of a light-scattering agent. Specifically, an OTP may contain 0.2-0.4% (w / v) of a light-scattering agent.

[0043] OTP can have any suitable scattering coefficient (μs') that mimics human tissue. For example, the scattering coefficient (μs') of OTP at 850 nm can be 10-20 cm⁻¹. -1 Specifically, the scattering coefficient (μs') of OTP at 850 nm can be 11-19 cm⁻¹. -1 12-18 cm -1 13-17 cm -1 14-16 cm -1 More specifically, the scattering coefficient (μs') of OTP at 850 nm can be 10⁻¹⁸ cm⁻¹. -1 The scattering coefficient (μs') of OTP at 808 nm can be 12-18 cm⁻¹. -1 Specifically, the scattering coefficient (μs') of OTP at 808 nm can be 13-17 cm⁻¹. -1 14-16 cm -1 More specifically, the scattering coefficient (μs') of OTP at 808 nm can be 13-16 cm⁻¹. -1 .

[0044] According to one specific aspect, an OTP may contain 0.001-0.004% (v / v) of a light absorber. Specifically, an OTP may contain 0.0015-0.0035% (v / v) or 0.002-0.003% (v / v) of a light absorber. The absorption coefficient (μa) of the OTP at 850 nm may be 0.02-0.08 cm⁻¹. -1 Specifically, the absorption coefficient (μa) of OTP at 850 nm can be 0.03-0.07 cm⁻¹. -1 0.04-0.06 cm -1 The absorption coefficient (μa) of OTP at 808 nm can range from 0.01 to 0.07 cm⁻¹. -1 Specifically, the absorption coefficient (μa) of OTP at 808 nm can be 0.02-0.06 cm⁻¹. -1 0.03-0.05 cm -1 .

[0045] OTP can be advantageously and easily adjusted by modifying the amounts of hot melt adhesive, light scattering agent, and light absorber to replicate the optical properties of various human tissues.

[0046] According to a second aspect, a method for forming an optical tissue phantom (OTP) is provided, the OTP comprising: a matrix containing a hot-melt adhesive and a light scattering agent and a light absorbing agent dispersed in the matrix, the method comprising:

[0047] - Mix hot melt adhesive, light scattering agent and light absorber to form a mixture;

[0048] - Heat the mixture for a predetermined period of time;

[0049] - Repeat the mixing and heating process; and

[0050] - After the repetition, the mixture is cooled to form the OTP.

[0051] Hot melt adhesives, light scattering agents, and light absorbers can be as described above.

[0052] Mixing and heating can be performed sequentially. For example, mixing can be performed before heating. Therefore, mixing and heating during repetition can also be sequential, such that mixing can be performed before heating during repetition. Mixing can be performed for any time period suitable to ensure a homogeneous mixture. For example, mixing can be performed for 1–10 minutes. Specifically, mixing can be performed for 2–9 minutes, 3–8 minutes, 4–7 minutes, or 5–6 minutes.

[0053] According to one particular aspect, the method may include melting the hot melt adhesive prior to mixing. Melting can be carried out at any temperature suitable for liquefying the hot melt adhesive. For example, melting can be carried out at 120-210°C. Specifically, melting can be carried out at temperatures of 130-200°C, 140-190°C, 150-180°C, and 160-170°C. Even more specifically, melting can be carried out at temperatures of 120-180°C. To facilitate melting, the hot melt adhesive can be reduced to smaller fragments.

[0054] Depending on one specific aspect, the mixing and heating may be repeated more than once. Specifically, the repetition can be two or three times. Thus, there can be two, three, or four cycles of mixing and heating. Repetition advantageously reduces the amount of bubbles and improves the homogeneity of the heated mixture. Repeated mixing and heating advantageously causes any bubbles in the mixture to burst due to temperature changes.

[0055] According to one particular aspect, mixing may include vacuum mixing. In this disclosure, vacuum mixing refers to mixing in an environment where the pressure is below atmospheric pressure. Vacuum mixing causes air bubbles present in the mixture to dissipate due to the pressure difference with the environment, and prevents the formation of bubbles due to the introduction of excess air by reducing the amount of air. Vacuum mixing can advantageously improve mixing efficiency by reducing or even eliminating repetition.

[0056] According to one specific aspect, mixing may include premixing the light scattering agent and the light absorbing agent. Premixing may include dispersing the light scattering agent and the light absorbing agent in water to form a dispersion. Dispersion may take place for 1–10 minutes. Specifically, dispersion may take place for 2–9 minutes, 3–8 minutes, 4–7 minutes, or 5–6 minutes.

[0057] The dispersion can be dried prior to mixing. Drying can be carried out at a temperature of 100-150°C. Premixing advantageously improves the dispersibility of the light absorber in the hot melt adhesive by promoting uniform interaction between the light absorber particles and water. Specifically, in the dispersion, the light absorber particles are suspended in water, and water acts as a medium to separate and uniformly distribute the particles. This interaction is influenced by surface chemistry, where stabilizers (e.g., surfactants or dispersants) in the formulation reduce particle aggregation by generating repulsive forces or steric hindrance between the particles.

[0058] During the drying of the dispersion, the premixed state ensures that the reagent particles are fully separated and uniformly distributed. As water evaporates, the particles maintain this uniform distribution, resulting in a homogeneous and stable dried light absorber layer. This process minimizes agglomeration, improves consistency, and provides a basis for the uniform distribution of the light absorber within the hot melt adhesive.

[0059] Heating can be performed at any temperature suitable for keeping the hot melt adhesive in the molten stage without negatively impacting shelf-life stability. According to one specific aspect, heating can be performed at temperatures of 120-210°C. Specifically, heating can be performed at temperatures of 130-200°C, 140-190°C, 150-180°C, and 160-170°C. Even more specifically, melting can be performed at temperatures of 120-180°C.

[0060] Heating the mixture for a predetermined period of time can be performed for any suitable time period. Depending on one specific aspect, the predetermined period of time can be 15-30 minutes. Specifically, heating can be performed for 20-25 minutes. As mentioned above, there can be two, three, or four cycles of mixing and heating. Therefore, the method can include a total heating time of 30-120 minutes, depending on the number of cycles and the predetermined period of time within each cycle.

[0061] Cooling of the mixture can be carried out at any suitable temperature. Depending on the specific aspect, cooling can be carried out at a temperature of 20-30°C. Cooling can be carried out at room temperature, thus advantageously eliminating the need for specialized equipment and saving energy. Cooling can be carried out for 30-60 minutes. Specifically, cooling can be carried out for 35-55 minutes or 40-50 minutes.

[0062] Therefore, the entire process of forming an OTP can take 60-180 minutes. Specifically, the OTP formation process can take 70-170 minutes, 80-160 minutes, 90-150 minutes, 100-140 minutes, or 110-130 minutes. Even more specifically, the OTP formation process can take 100-140 minutes. Thus, the method is advantageously much faster than previous methods.

[0063] The present invention has now been generally described, and it will be more readily understood by referring to the following embodiments, which are provided by way of example and are not intended to be limiting.

[0064] Example

[0065] Example 1

[0066] Materials and methods

[0067] Black ink (1 µL) (Kin's liquid ink) was used as a light absorber to modify the absorption coefficient, and titanium dioxide (TiO2) powder (0.1 g) (AEROXIDE® TiO2 P 25) was used as a light scattering agent to control the reduced scattering coefficient. 85.53 mL of EVA (ethylene-vinyl acetate copolymer) hot melt adhesive (Delixi Electric, China, hot melt adhesive sticks) was used as the phantom matrix.

[0068] Figure 1 The diagram illustrates a general method for phantom fabrication. The EVA hot melt adhesive sticks used have a diameter of 11 mm and a length of 150 mm, resulting in a volume of 14.255 mL per stick. An aluminum foil container with a diameter of 6.5 cm and a height of 4 cm is used. First, six EVA sticks are broken into small pieces to facilitate melting. The pieces are then placed in the aluminum foil container, which is placed on a heating platform set to a constant temperature of 180°C. The adhesive is heated for 30 minutes to melt it.

[0069] Add TiO2 and ink to the molten gel and mix manually with a glass rod for 5 minutes. Then heat the mixture for another 20 minutes, followed by vigorous stirring to ensure homogeneity. Repeat this 20-minute heating cycle. Finally, allow the mixture to cool naturally for 45 minutes.

[0070] Three other sets of experiments were conducted using 0.2 g, 0.3 g, and 0.4 g of TiO2, respectively.

[0071] Example 2

[0072] Materials and methods

[0073] Three sets of experiments were conducted using 1 µL, 2 µL, and 3 µL of ink, respectively. In each experiment, 2 mL of water was added to TiO2 powder (0.1 g) and ink in an aluminum foil container with a diameter of 6.5 cm and a height of 4 cm to promote thorough mixing of the ink and titanium dioxide powder. The resulting solution was evaporated to remove the water, leaving a well-mixed combination of ink and titanium dioxide powder.

[0074] Next, add 6 EVA hot melt adhesive sticks (85.53 mL) and melt them at 180°C. Stir the mixture to achieve homogeneity. Then reheat the mixture for 20 minutes. Finally, allow the mixture to cool naturally for 45 minutes.

[0075] Characterization

[0076] Time-resolved near-infrared spectroscopy (TD-NIRS)

[0077] The measuring instrument used was time-domain or time-resolved near-infrared spectroscopy (TD-NIRS). The phantom was illuminated with laser pulses with a resolution ranging from tens to hundreds of picoseconds. A 'time-point spread function (TPSF)' was constructed from the time-series intensity of the escape light at picosecond resolution. The spread equation modeled the light pulses traveling through the uniform semi-infinite phantom. By analyzing the shape, attenuation, and time delay of the TPSF signal, the absolute values ​​of optical properties such as absorption and scattering parameters were derived.

[0078] The detector was securely attached to the surface of the phantom and secured with a strap. The distance between the light source and the detector was 2.5 cm. Measurements were performed in a dark room to minimize ambient light noise.

[0079] Results and discussion

[0080] Example 1

[0081] Time-resolved near-infrared spectroscopy (TD-NIRS)

[0082] The TPSF data measured by the TD-NIRS system are provided in Figure 2(a). As shown in Figure 2(b), the scattering coefficient exhibits a clear linear increase with increasing TiO2 content.

[0083] Example 2

[0084] Time-resolved near-infrared spectroscopy (TD-NIRS)

[0085] The TPSF data measured by the TD-NIRS system are shown in Figure 3(a). As shown in Figure 3(b), the absorption coefficient exhibits a clear linear increase.

[0086] In the TPSF signal of the EVA+ ink bulk motif (Figure 3(a)), the peak shifts slightly to an earlier time delay as the ink concentration increases. This shift occurs because the increase in ink volume improves the absorption coefficient of the bulk motif. Consequently, the path length of photons from the light source is shortened, resulting in a shorter photon capture time and causing the peak to shift to the left.

[0087] A volumetric mold formed using 0.1 g of TiO2 and 2 µL of ink exhibits optical properties that approximate those of normal human breast tissue, with a measured μa of 0.0512 cm⁻¹. -1 And μs' is 9.0516 cm. -1 .

[0088] Although exemplary embodiments have been described above, those skilled in the art will understand that various changes can be made without departing from the present invention.

Claims

1. An optical tissue phantom (OTP), the optical tissue phantom (OTP) comprising: - A matrix containing hot melt adhesive; and - Light scattering agents and light absorbers dispersed in the matrix.

2. The OTP according to claim 1, wherein the light scattering agent comprises a metal oxide, a polymer, or a combination thereof.

3. The OTP according to claim 1, wherein the light absorber comprises ink, toner, toner, or a combination thereof.

4. The OTP according to claim 1, wherein the OTP comprises 0.1-0.5% (w / v) of the light scattering agent.

5. The OTP of claim 1, wherein the OTP comprises 0.001-0.004% (v / v) of the light absorber.

6. The OTP according to claim 1, wherein the scattering coefficient (μs') of the OTP at 850 nm is 10-20 cm⁻¹. -1 .

7. The OTP according to claim 1, wherein the scattering coefficient (μs') of the OTP at 808 nm is 12-18 cm⁻¹. -1 .

8. The OTP according to claim 1, wherein the absorption coefficient (μa) of the OTP at 850 nm is 0.02-0.08 cm⁻¹. -1 .

9. The OTP according to claim 1, wherein the absorption coefficient (μa) of the OTP at 808 nm is 0.01-0.07 cm⁻¹. -1 .

10. A method for forming an optical tissue phantom (OTP), the optical tissue phantom (OTP) comprising: a matrix comprising a hot melt adhesive and a light scattering agent and a light absorbing agent dispersed in the matrix, the method comprising: - Mix hot melt adhesive, light scattering agent and light absorber to form a mixture; - Heat the mixture for a predetermined period of time; - Repeat the mixing and heating process; as well as - After the repetition, the mixture is cooled to form the OTP.

11. The method of claim 10, wherein the method comprises melting the hot melt adhesive prior to the mixing.

12. The method of claim 10, wherein the repetition is repeated more than once.

13. The method of claim 10, wherein the mixing comprises vacuum mixing.

14. The method of claim 10, wherein the mixing comprises premixing the light scattering agent and the light absorbing agent.

15. The method of claim 14, wherein the premixing comprises dispersing the light scattering agent and the light absorbing agent in water to form a dispersion.

16. The method of claim 15, wherein the method comprises drying the dispersion.

17. The method of claim 10, wherein the heating is performed at a temperature of 120-210°C.

18. The method of claim 10, wherein the predetermined time period is 15-30 minutes.

19. The method of claim 10, wherein the cooling is performed at a temperature of 20-30°C.

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