Calibrator for calibrating collagen content determination and method and system for measuring collagen content

Abstract

The invention relates to a calibration piece for calibrating collagen content determination and a method and a system for measuring collagen content. The method comprises the following steps: performing energy scanning on a measured object containing collagen through energy CT equipment to obtain CT scanning data of the measured object; a collagen scan content is extracted from the CT scan data based on a characteristic parameter of collagen and a characteristic parameter of a pure substance that may be contained in the measured object. The calibration member comprises a plurality of sets of collagen-pure substance component mixtures, each pure substance component comprises a pure substance, and for each pure substance component, at least two sets of collagen-pure substance component mixtures with different collagen contents are provided. And when the calibration piece is subjected to energy scanning by the energy CT equipment, obtaining a corresponding relationship between the collagen scanning content and the actual collagen content for at least two groups of collagen-pure substance component mixtures with the same pure substance component, and obtaining the actual collagen content based on the extracted collagen scanning content and the corresponding relationship.

Description

Technical Field

[0001] This invention relates to the field of medical testing, and more specifically to calibration devices for calibrating collagen content determination, and methods and systems for measuring collagen content. Background Technology

[0002] Collagen (also known as collagen protein) is essential for living organisms. Especially for the human body, collagen is the most abundant protein, found throughout various tissues and organs. It is a crucial structural protein component of connective tissues such as skin, bone and cartilage, teeth, tendons, ligaments, and blood vessels. It participates in physiological functions including cell morphology, proliferation, differentiation, adhesion, migration, individual development, reproduction, information transmission, blood clotting, and tissue repair. It is also related to skin aging and the prevention and treatment of certain diseases. Therefore, measuring the collagen content in the human body is essential in clinical testing.

[0003] While various analytical methods commonly used in biochemistry and analytical chemistry can quantify collagen, they are extremely cumbersome. High-performance liquid chromatography (HPLC), another method, not only requires specialized equipment, increasing complexity, but also has significant limitations. Furthermore, none of these methods can perform detection on living organisms; ex vivo samples must be obtained first for analysis.

[0004] In addition to collagen, the human body often contains other elements (for example, calcium in bones and iron in the liver), which further increases the difficulty of accurately measuring the collagen content in various parts of the body.

[0005] Therefore, there is an urgent need for a new technology that can conveniently and accurately measure the collagen content of an object. Summary of the Invention

[0006] The present invention aims to overcome the aforementioned and / or other problems in the prior art. By employing the collagen content measurement method and system of the present invention, and using an energy-based CT (computed tomography) device to perform an energy scan on a measurement object containing collagen and other pure substances, the collagen content of the measurement object can be directly extracted from the obtained CT scan data—something that has never been achieved with any existing technology. Furthermore, by scanning the calibration piece provided by the present invention for calibrating collagen content determination, the collagen content measurement method and system of the present invention can further improve measurement accuracy.

[0007] According to a first aspect of the present invention, a method for measuring collagen content is provided, which may include the steps of: a) performing an energy scan on a measurement object containing collagen using an energy CT device to obtain CT scan data of the measurement object; and b) extracting the collagen scan content of the measurement object from the CT scan data of the measurement object based on characteristic parameters of collagen and characteristic parameters of pure substances that may be contained in the measurement object.

[0008] According to a second aspect of the invention, a system for measuring collagen content is provided, which may include an energy CT device and a computing unit. The energy CT device is configured to perform an energy scan on a measurement object containing collagen to obtain CT scan data of the measurement object. The computing unit is configured to extract the collagen scan content of the measurement object from the CT scan data of the measurement object based on characteristic parameters of collagen and characteristic parameters of pure substances that may be contained in the measurement object.

[0009] Because collagen is not a pure substance, its characteristic parameters have always been difficult to determine. However, through extensive experiments and calculations, the inventors have for the first time determined the characteristic parameters of collagen. This breakthrough has made it possible to obtain the collagen content in a measured object using energy-based CT scanners. The multi-level energy of energy-based CT scanners allows the CT scan data obtained by scanning a measured object to contain energy scan data corresponding to multiple energy levels. This energy scan data is correlated with the characteristic parameters and content of each component in the measured object. Therefore, based on the characteristic parameters of collagen and the characteristic parameters of other known pure substances, the collagen content can be obtained from the CT scan data. Because it is obtained directly from the CT scan data, it is also referred to as "collagen scan content" in this paper.

[0010] As mentioned above, because collagen is not a pure substance, it does not have a true corresponding chemical formula. However, the inventors discovered that the characteristic parameters of collagen can be determined by simulating a chemical formula for collagen.

[0011] The chemical formula for the above simulation can be any of the following: C M C 5M H 9M N M O 3M C 6M H 14M N 2M O 3M C 169858 M H 990099M N 29979M O 403125M Na 870M P 323M S 624M Cl 846M K 256M Or C 82431M H 950495M N 15703M O 465000M Na 2175M P 7104M S 2807M Cl 846M , where M > 0.

[0012] The inventors also discovered that the characteristic parameters of collagen have corresponding ranges under different energy voltages, and the minimum and maximum values ​​of these ranges are respectively the characteristic parameters. min and characteristic parameters max Where 0 < characteristic parameter min <1, 0 < Feature parameters max <1, characteristic parameters min < Feature parameters max Furthermore, as the energy voltage increases, the characteristic parameters... min and the feature parameters max They are all monotonically decreasing.

[0013] Specifically, when the energy voltage is in the range of 40keV to 140keV, the characteristic parameters min The characteristic parameter is within the range of 0.20750 to 0.13740. max It falls within the range of 0.28324 to 0.15214.

[0014] According to a third aspect of the present invention, a calibration device for calibrating collagen content determination is provided, comprising a mixture of multiple sets of collagen-pure substance components, each pure substance component comprising a pure substance, and for each pure substance component, at least two sets of collagen-pure substance component mixtures with different collagen contents are provided. When the calibration device is energy-scanned by an energy CT device, at least two sets of CT scan data are obtained for at least two sets of collagen-pure substance component mixtures with the same pure substance component. Collagen scan content is extracted from the at least two sets of CT scan data based on characteristic parameters of collagen and characteristic parameters of the pure substances in the pure substance components. A correspondence between collagen scan content and actual collagen content is obtained based on the extracted collagen scan content and the collagen content of each of the at least two sets of collagen-pure substance component mixtures.

[0015] The collagen content measurement method of the present invention may further include the following steps: c) performing an energy scan on the above-mentioned calibrator of the present invention using the energy CT device to obtain CT scan data of at least two sets of collagen-pure substance mixtures with different collagen contents for pure substances that may be contained in the measured object; d) extracting the collagen scan content from the at least two sets of CT scan data based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object; e) obtaining a correspondence between the collagen scan content and the actual collagen content based on the extracted collagen scan content and the collagen content of each of the at least two sets of collagen-pure substance mixtures; and f) obtaining the actual collagen content in the measured object based on the collagen scan content of the measured object extracted in step b) and the correspondence between the collagen scan content and the actual collagen content. Accordingly, in the collagen content measurement system of the present invention, the energy CT device may be further configured to: perform energy scanning on the above-mentioned calibrator of the present invention to obtain CT scan data of at least two sets of collagen-pure substance mixtures with different collagen contents for pure substances that may be contained in the measured object; the calculation unit may be further configured to: extract collagen scan content from the at least two sets of CT scan data based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object; obtain a correspondence between collagen scan content and actual collagen content based on the extracted collagen scan content and the actual collagen content of each of the at least two sets of collagen-pure substance mixtures; and obtain the actual collagen content in the measured object based on the extracted collagen scan content and the correspondence between collagen scan content and actual collagen content.

[0016] Although, as described above, the present invention has been able to obtain the collagen content in a measured object based on CT scan data obtained from scanning the object with an energy CT device by pioneering the determination of collagen characteristic parameters, the inventors have also designed a calibration device specifically for calibrating collagen content determination in order to further improve the measurement accuracy.

[0017] The inventors discovered that for mixtures containing collagen and other pure substances, the actual collagen content in the mixture has a one-to-one, approximately linear relationship with the collagen scan content obtained from CT scan data using the method and system of the present invention under the same energy CT device. Based on this significant discovery, the inventors designed a calibration device that cleverly incorporates multiple mixtures of collagen-pure substance components with varying collagen contents. By performing an energy scan on the calibration device, the correspondence between the collagen scan content obtained from the CT scan data and the actual collagen content in the different mixtures can be determined. With this correspondence and the determined collagen characteristic parameters as described above, the collagen content of any object containing collagen and the same pure substance component can be conveniently and accurately measured by scanning with the energy CT device.

[0018] It should be noted that even with the same energy CT scanner, the system parameters can change over time. This can lead to different CT scan data even when scanning mixtures with the same collagen and pure component content, resulting in different collagen scan values ​​extracted from these data. The aforementioned calibration device effectively corrects for the errors caused by these system parameter changes. By scanning the calibration device with the current energy CT scanner, a precise correspondence between the collagen scan value and the actual collagen content under the current system parameters can be obtained.

[0019] The calibration device of this invention is specifically designed for the above-mentioned collagen content measurement. Existing technologies, because they cannot perform collagen measurements using CT equipment, do not have calibration devices designed to include mixtures of multiple collagen-pure substance components, with each pure substance component comprising one pure substance, and for each pure substance component, at least two mixtures of collagen-pure substance components with different collagen contents. However, it should be noted that the calibration device of this invention is not limited to the above-mentioned collagen content measurement; it can also be scanned with an energy CT device before or after the collagen content measurement to obtain the correspondence between the scanned collagen content and the actual collagen content. The shorter the time interval between the calibration performed before or after the subsequent collagen content measurement, the higher the accuracy of the measurement.

[0020] Furthermore, the calibration components of the present invention may include various types, such as phantoms and mixed solutions of collagen-pure components.

[0021] Taking a phantom as an example, as mentioned earlier, due to the inability of existing technology to perform collagen measurements using CT equipment, there has never been a calibration phantom for collagen determination. However, this invention provides such a calibration phantom, which may include multiple regions, each region having a material body containing a collagen-pure substance component. Each pure substance component includes one pure substance, and for each pure substance component, there are at least two sets of collagen-pure substance component material bodies with different collagen contents. By scanning this phantom, an energy CT device can obtain a high-precision correspondence between the scanned collagen content and the actual collagen content for a collagen mixture containing a certain pure substance component, as needed. By scanning any object containing collagen and the pure substance component with this energy CT device, the collagen content of the object can be conveniently and accurately obtained based on the correspondence and the characteristic parameters of collagen.

[0022] As previously stated, the inventors discovered through numerous experiments that there is a corresponding relationship between the actual collagen content in a mixture containing collagen and other pure substances and the collagen scan content obtained based on CT scan data using the method and system of this invention. This correspondence can be represented by a linear function: y = kx + b, where y is the actual collagen content and x is the collagen scan content.

[0023] According to a fourth aspect of the present invention, a computer-readable storage medium is provided having encoded instructions recorded thereon, which, when executed, enable the method of the present invention for measuring collagen content.

[0024] According to a fifth aspect of the present invention, a computer program product is provided, comprising a computer program that, when executed, enables the method of the present invention for measuring collagen content.

[0025] Other features and aspects of the invention will become clearer from the following detailed description taken in conjunction with the accompanying drawings. Attached Figure Description

[0026] The invention can be better understood by describing exemplary embodiments of the invention in conjunction with the accompanying drawings, in which: Figure 1 A flowchart of a method for measuring collagen content according to an embodiment of the present invention is shown; Figure 2 A schematic diagram of a calibration piece for calibrating collagen content determination according to an embodiment of the present invention is shown; Figure 3 This demonstrates scanning using an energy CT scanner. Figure 2 The straight line showing the relationship between the scanned collagen content and the actual collagen content obtained by fitting the calibration piece shown in the figure; Figure 4 A flowchart illustrating a variation of the method for measuring collagen content according to an embodiment of the present invention is shown; Figures 5-7 The regression lines between the collagen scan content obtained from measuring collagen-calcium chloride mixed solutions using the collagen content measurement method of this invention under different scanning conditions and calcium concentrations were compared with the actual collagen content of the collagen-calcium chloride mixed solutions; and Figure 8 A schematic block diagram of a system for measuring collagen content according to an embodiment of the present invention is shown. Detailed Implementation

[0027] The present invention will be further described below with reference to specific embodiments and accompanying drawings. More details are set forth in the following description in order to provide a full understanding of the present invention. However, the present invention can obviously be implemented in many other ways different from those described herein. Those skilled in the art can make similar extensions and derivations based on actual application situations without departing from the spirit of the present invention. Therefore, the scope of protection of the present invention should not be limited by the content of this specific embodiment.

[0028] Unless otherwise defined, the technical or scientific terms used in the claims and description shall have the ordinary meaning understood by one of ordinary skill in the art to which this invention pertains. The terms "first," "second," and similar terms used in the description and claims of this application do not indicate any order, quantity, or importance, but are merely used to distinguish different components. The terms "an" or "a" and similar terms do not indicate a quantity limitation, but rather indicate the presence of at least one. The terms "comprising" or "including" and similar terms mean that the element or object preceding "comprising" or "including" encompasses the element or object listed following "comprising" or "including" and its equivalents, and do not exclude other elements or objects. The terms "connected" or "linked" and similar terms are not limited to physical or mechanical connections, nor are they limited to direct or indirect connections.

[0029] According to an embodiment of the present invention, a method for measuring collagen content is provided.

[0030] Figure 1 A flowchart of a method 100 for measuring collagen content according to an embodiment of the present invention is shown. Figure 1 As shown, the method 100 may include steps 110 and 120.

[0031] In step 110, the measurement object containing collagen can be energy scanned using an energy CT device to obtain CT scan data of the measurement object.

[0032] Energy CT equipment can be, for example, dual-energy CT equipment, tri-energy CT equipment, or CT equipment with more energy levels. When performing an energy scan, a dual-energy CT equipment can acquire scan data from two different energies of X-rays (e.g., 80 keV and 140 keV); a tri-energy CT equipment can acquire scan data from three different energies of X-rays; and so on. Different substances exhibit different attenuation characteristics under X-rays of different energies.

[0033] A pure substance is a substance that can be expressed by a definite chemical formula, and can include elements (e.g., sodium (Na), calcium (Ca), etc.) or compounds (e.g., calcium chloride (CaCl2), etc.). For example, a measuring object containing collagen could be a human tendon, which, in addition to collagen, is very likely to contain calcium. Another example is a measuring object containing collagen, which could be a human liver, which, in addition to collagen, is very likely to contain iron.

[0034] Taking the pure substance contained in the measured object as an example, dual-energy (such as 80 keV and 140 keV) CT equipment can be used to perform energy scanning on the measured object. Of course, tri-energy CT equipment, quad-energy CT equipment or even CT equipment with more energy levels can also be used to perform energy scanning on the measured object to ensure that the CT scan data obtained can reflect the different attenuation of collagen and calcium at at least two different energies.

[0035] Returning to method 100, next, in step 120, the collagen scan content of the measured object can be extracted from the CT scan data of the measured object based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object.

[0036] Taking the example of measuring an object containing collagen and calcium, the CT scan data obtained in step 110 includes attenuation data corresponding to two energies: 80 keV and 140 keV. Mathematical modeling of these two sets of attenuation data yields two equations corresponding to 80 keV and 140 keV, respectively. These equations are related to the content of collagen and calcium (expressed as, for example, concentration, with units of mg / ml) and the characteristic parameters (mass attenuation coefficients) of collagen and calcium at energies of 80 keV and 140 keV, respectively.

[0037] For example, we can obtain the system of equations (1): CT 80KeV =Collagen content Collagen feature parameters 80KeV +Ca content Ca characteristic parameters 80KeV CT 140KeV = Collagen content Collagen feature parameters140KeV +Ca content Ca characteristic parameters 140KeV

[0038] The above CT 80KeV and CT 140KeV The images show CT scan data (linear attenuation coefficient, which can be calculated from CT values) of the measured object at energies of 80 keV and 140 keV, respectively, and the Collagen characteristic parameters. 80KeV and Collagen feature parameters 140KeV These are the characteristic parameters (mass decay coefficient) of collagen at energies of 80 keV and 140 keV, respectively, and the Ca characteristic parameter. 80KeV and Ca characteristic parameters 140KeV The values ​​of these parameters (mass decay coefficients) represent the characteristic parameters of calcium at energies of 80 keV and 140 keV, respectively. By substituting these parameter values ​​into the two equations above, the collagen content and calcium content can be obtained.

[0039] However, calcium is a pure substance with a clearly defined molecular formula (Ca), its composition is known, and its characteristic parameters at different energies are also known. Collagen, on the other hand, is not a pure substance, and its specific composition cannot be determined. Therefore, its characteristic parameters have always been difficult to determine, which has become a major technical obstacle to separating collagen from other pure substances using energy-based CT equipment. After extensive experiments and calculations, the inventors finally overcame this difficulty and, for the first time, calculated the characteristic parameters of collagen at different energies.

[0040] As mentioned above, collagen does not have a true corresponding chemical formula. The inventors boldly simulated a chemical formula for collagen to determine its characteristic parameters. There are many such simulated chemical formulas, for example: C... M C 5M H 9M N M O 3M C 6M H 14M N 2M O 3M C 169858M H 990099M N 29979M O 403125M Na 870M P 323M S 624M Cl 846M K 256M Or C 82431M H 950495M N 15703M O 465000 M Na 2175M P 7104M S2807M Cl 846M Where M > 0. Collagen can be simulated as any of the chemical formulas in the examples above, and the characteristic parameters of collagen can be obtained based on that chemical formula. These simulated chemical formulas are not the actual chemical formulas of collagen, but the collagen content calculated by substituting the collagen characteristic parameters obtained from them into the above equations is very close to the actual collagen content. This also shows that the characteristic parameters obtained from these simulated chemical formulas are very close to the actual characteristic parameters of collagen.

[0041] The characteristic parameters of a substance differ under different energy voltages, and collagen is no exception. This invention determines its characteristic parameters by simulating collagen as a chemical formula. Because different simulated chemical formulas exist, the characteristic parameters of collagen are not a single value under different energy voltages, but rather a corresponding range: [characteristic parameters] min , Feature parameters max ], where 0 < feature parameter min <1, 0 < Feature parameters max <1, characteristic parameters min <Feature parameters max Any value within this range can be used as a characteristic parameter of collagen at the corresponding energy voltage. Substituting this characteristic parameter into the above equation set (1) will allow the collagen content to be calculated.

[0042] As the energy voltage increases, the characteristic parameters min and the feature parameters max They will decrease monotonically, respectively. For example, when the energy voltage is in the range of 40keV to 140keV, the characteristic parameters... min The characteristic parameter monotonically decreases from 0.20750 to 0.13740. max It decreases monotonically from 0.28324 to 0.15214. Table 1 below shows the range of characteristic parameters of collagen at various energy voltages.

[0043]

[0044] Table 1: Range of collagen characteristic parameters under different energy voltages

[0045] However, when a chemical formula is used to simulate collagen, the characteristic parameters of collagen at various energy voltages can be a single value. For example, if the chemical formula C... 169858M H 990099M N 29979M O 403125M Na 870M P 323M S 624M Cl 846M K 256MBy simulating collagen, we can obtain the characteristic parameters of collagen under various energy voltages, as shown in Table 2 below.

[0046]

[0047] Returning to step 110, still using the example of measuring the content of collagen and calcium in an object, and using the chemical formula C... 169858M H 990099 M N 29979M O 403125M Na 870M P 323M S 624M Cl 846M K 256M To simulate collagen, the characteristic parameters of collagen at energy voltages of 80 keV and 140 keV are obtained as 0.18118 and 0.15204, respectively. The characteristic parameters of calcium at energy voltages of 80 keV and 140 keV are known, at 0.36550 and 0.17730, respectively. The collagen content can then be calculated from the above equation set (1).

[0048] Undoubtedly, the inventor's determination of collagen characteristic parameters is a breakthrough, enabling the collagen content measurement method of this invention to conveniently determine the collagen content of the object to be measured simply by scanning the object with an energy CT device, which is something that no existing collagen content measurement technology can do.

[0049] Furthermore, the inventors have discovered that when scanning conditions change (including, for example, changes in calcium content), for mixtures containing collagen and other pure substances (e.g., calcium chloride), the actual collagen content in the mixture correlates well with the collagen scan content measured using the collagen measurement method of the present invention under the same energy CT equipment, exhibiting a good linear fit, wherein R... 2 =0.969~0.997 (R) 2 The coefficient of determination (closer to 1 indicates a better fit) is p < 0.001 (p < 0.05 indicates statistical significance; a smaller p-value suggests a stronger likelihood that the result is due to a true effect rather than random error). This indicates that the actual collagen content has an approximately linear relationship with the collagen scan content measured using the collagen measurement method of this invention under the same energy CT equipment. Based on this significant discovery, the inventors specifically designed a calibration device for calibrating collagen content determination.

[0050] Figure 2 The diagram schematically illustrates such a calibration element 200, which may comprise a mixture of multiple sets of collagen-pure components (mixture 1 to mixture 2). n (where n is a positive integer greater than 1). Each pure substance component (pure substance component 1 ~ pure substance component 2)n This includes a pure substance, and for each pure substance component, there are at least two mixtures of collagen-pure substance components with different collagen contents. While the collagen contents differ, the contents of the pure substance components may be the same or different. For example, Figure 2 Mixture 1 and Mixture 2 shown are both combinations of (collagen + pure component 1), containing different amounts of collagen (content 1 and content 2 respectively), but the amount of pure component 1 is the same in both (content 1). For example, Figure 2 Mixtures 4 and 5 shown are both combinations of (collagen + pure component 2), with different collagen contents (content 2 and content 3 respectively) and different contents of pure component 2 (content 1 and content 2 respectively).

[0051] For example, calcium, iron, and sodium chloride can each be considered a pure substance component. If the pure substance component includes three substances (calcium), (iron), and (sodium chloride), then there are at least two mixtures with different collagen contents (collagen + calcium), at least two mixtures with different collagen contents (collagen + iron), and at least two mixtures with different collagen contents (collagen + sodium chloride). As mentioned earlier, the content of the pure substance components can be the same or different depending on the collagen content. For example, for two mixtures with different collagen contents (collagen + calcium), the calcium content is different from each other.

[0052] When Figure 2 The calibration piece 200 was scanned using an energy CT scanner, as shown in the figure, to obtain the results corresponding to mixture 1 to mixture 2. n CT scan data for each of the following (CT scan data 1 ~ CT scan data) n For at least two sets of collagen-pure substance mixtures with the same pure substance component, any two sets can be selected from their CT scan data. For example, for mixtures 1, 2, and 3, which all contain pure substance component 1, any two of their corresponding CT scan data can be selected (e.g., CT scan data 1 and CT scan data 3). Collagen scan content can be extracted from CT scan data 1 and CT scan data 3 based on the characteristic parameters of collagen and the characteristic parameters of the pure substance in pure substance component 1, for example, collagen scan content 1 and collagen scan content 3. Based on two points (collagen scan content 1, actual collagen content 1) and (collagen scan content 3, actual collagen content 3) with collagen scan content on the horizontal axis and actual collagen content on the vertical axis, a straight line representing the correspondence between collagen scan content and actual collagen content can be fitted, such as... Figure 3 As shown in the image.

[0053] Taking the pure substance component 1 as calcium and scanning with a dual-energy (80 keV and 140 keV) CT device as an example, the attenuation data corresponding to the two energies of 80 keV and 140 keV contained in the CT scan data 1 can be mathematically modeled to obtain the following set of equations (2): CT scan data 1 80KeV =Collagen content Collagen feature parameters 80KeV +Ca content Ca characteristic parameters 80KeV CT scan data 1 140KeV = Collagen content Collagen feature parameters 140KeV +Ca content Ca characteristic parameters 140KeV

[0054] The characteristic parameters of collagen at energies of 80 keV and 140 keV can be determined as previously described, and will not be repeated here. The collagen content obtained by solving the above system of equations (2) is the collagen scanning content 1 extracted from CT scan data 1.

[0055] Similarly, mathematical modeling can be performed on the attenuation data corresponding to the two energies of 80 keV and 140 keV contained in CT scan data 3, resulting in the following set of equations (3): CT scan data 3 80KeV =Collagen content Collagen feature parameters 80KeV +Ca content Ca characteristic parameters 80KeV CT scan data 3 140KeV = Collagen content Collagen feature parameters 140KeV +Ca content Ca characteristic parameters 140KeV

[0056] Similarly, the Collagen content obtained by solving the above system of equations (3) is the collagen scan content 3 extracted from the CT scan data 3.

[0057] Existing calibration kits have never included mixtures of multiple collagen-pure component groups as described in the calibration kit of this invention. Each pure component group comprises one pure substance, and for each pure component group, there are at least two mixtures of collagen-pure component groups with different collagen contents. With the ability to obtain collagen characteristic parameters, energy CT equipment can easily obtain a highly accurate correlation between the scanned collagen content and the actual collagen content for a specific pure component and collagen combination simply by scanning the novel calibration kit. This ensures that collagen content measurements are closer to actual values.

[0058] It should be noted that, despite the above combination Figure 2 and Figure 3 The described embodiment is based on fitting two points to obtain the correspondence between the scanned collagen content and the actual collagen content. However, it can be understood that the more points the fitting is based on, the closer the fitted straight line will be to the true correspondence between the scanned collagen content and the actual collagen content.

[0059] With the aforementioned specially designed calibration device, the method 100 for measuring collagen content according to an embodiment of the present invention may further include steps 130 to 160, such as... Figure 4 As shown.

[0060] In step 130, the calibration piece of the present invention can be energy scanned by the energy CT device to obtain CT scan data of at least two sets of collagen-pure substance mixtures with different collagen contents for pure substances that may be contained in the measured object.

[0061] As described above Figure 2 The calibration component 200 of the present invention may include a mixture of multiple sets of collagen-pure components (mixture 1 to mixture 2). n Each pure substance component (pure substance component 1 to pure substance component 2) n The sample includes a pure substance, and for each pure substance component, there are at least two sets of collagen-pure substance mixtures with different collagen contents. Taking the sample containing collagen and calcium as an example, scanning the aforementioned calibration piece 200 with an energy CT device (still using a dual-energy CT device of 80 keV and 140 keV as an example) yields at least two sets of CT scan data for collagen-calcium mixtures with different collagen contents, for example, CT scan data 1 and CT scan data 3 corresponding to mixture 1 and mixture 3, respectively.

[0062] In step 140, the collagen scan content can be extracted from the at least two sets of CT scan data based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object.

[0063] As described above Figure 2 andFigure 3 As mentioned above, thanks to the inventor's determination of collagen characteristic parameters, by mathematically modeling the attenuation data corresponding to 80 keV and 140 keV contained in CT scan data 1 and CT scan data 3, the collagen scan content 1 and collagen scan content 3 can be obtained respectively.

[0064] Next, in step 150, the correspondence between collagen scan content and actual collagen content can be obtained based on the extracted collagen scan content and the actual collagen content of each of the mixtures of the at least two sets of collagen-pure substance components.

[0065] Still in the same combination as above Figure 2 and Figure 3 Based on the aforementioned collagen scan content 1 and collagen scan content 3, as well as the actual collagen content (actual collagen content 1 and actual collagen content 3) in mixtures 1 and 3, two points can be obtained: (collagen scan content 1, actual collagen content 1) and (collagen scan content 3, actual collagen content 3). A straight line representing the correspondence between collagen scan content and actual collagen content can be fitted using these two points. Similarly, the more points the fitting is based on, the closer the fitted straight line will be to the true correspondence between collagen scan content and actual collagen content.

[0066] Alternatively, a linear function y=kx+b can be used to directly represent the correspondence between the scanned collagen content and the actual collagen content, where y is the actual collagen content and x is the scanned collagen content.

[0067] By substituting the x-coordinate and y-coordinate of the two points (collagen scan content 1, actual collagen content 1) and (collagen scan content 3, actual collagen content 3) into the above y=kx+b, we can calculate: k = (actual collagen content 3 - actual collagen content 1) / (scanned collagen content 3 - scanned collagen content 1). b = Actual collagen content 1 - Scanned collagen content 1 (Actual collagen content 3 - Actual collagen content 1) / (Collagen scan content 3 - Collagen scan content 1).

[0068] Steps 130-150 above can be used to obtain for the first time the correspondence between the collagen scan content and the actual collagen content when scanning a mixture of collagen and a certain pure substance component (e.g., collagen + calcium) with the energy CT device. This is to facilitate the subsequent determination of the collagen content in any mixture of the same composition (e.g., collagen + calcium) based on this correspondence. Alternatively, steps 130-150 above can be used to calibrate the previously obtained correspondence between the collagen scan content and the actual collagen content when scanning a mixture of collagen and a certain pure substance component (e.g., collagen + calcium) with the energy CT device, so as to ensure that the collagen content of the measured object can be obtained based on a more accurate correspondence between the collagen scan content and the actual collagen content.

[0069] Next, in step 160, the collagen scan content (e.g., collagen scan content) of the measured object extracted in step 120 can be used as a basis. 测量物体 The actual collagen content in the measured object is obtained by comparing the collagen scan content obtained in step 150 with the actual collagen content.

[0070] For example, it can be Figure 3 Find the horizontal axis representing the collagen scan content on the straight line obtained by fitting. 测量物体 The point on the y-axis theoretically represents the actual collagen content of the measured object, so using it as the collagen content for measurement is almost identical to the actual value. Alternatively, x can be represented as the collagen scan content. 测量物体 Substitute the values ​​into the linear function y=kx+b above to calculate the actual collagen content of the measured object.

[0071] Although the collagen scan content obtained through steps 110 and 120 can already be used as the collagen content determination value, steps 130 to 160 above can further improve the measurement accuracy of the collagen content determination method of the present invention, so that the obtained collagen content determination value is closer to the actual value.

[0072] It should be noted that the numbering of the steps above is for ease of description only and does not mean that steps 110-160 must be performed in the order of the numbers. For example, steps 110-120 can be performed after or before steps 130-150, or simultaneously with steps 130-150.

[0073] Furthermore, as the system parameters of an energy CT scanner may shift after a period of use, the energy CT scan data may deviate from previous energy CT scan data. Therefore, to ensure higher accuracy of the collagen scan content-actual collagen content correspondence when measuring collagen content in an object using an energy CT scanner, the object and the calibration piece of this invention can be scanned simultaneously with energy CT, or the calibration piece of this invention can be scanned with the same energy CT scanner before each collagen content measurement of the object, so as to calibrate the collagen scan content-actual collagen content correspondence to a state suitable for the current system parameters.

[0074] However, it is understandable that, depending on the actual situation, it is not always necessary to recalibrate the correspondence between the scanned collagen content and the actual collagen content using the calibration kit of this invention every time collagen content is measured using an energy-based CT scanner. Instead, the correspondence obtained from the most recent calibration using the calibration kit of this invention can be used directly. For example, the time since the last calibration may be relatively recent, or recalibration may be sufficient to meet the accuracy requirements for collagen content measurement, or the time for measuring collagen content may be tight.

[0075] Optionally, the calibration component of the present invention can be a phantom. According to one embodiment of the present invention, the phantom may include multiple regions, each region having a material body of a collagen-pure substance component, each pure substance component comprising one pure substance, and for each pure substance component having at least two sets of collagen-pure substance component material bodies with different collagen contents. Since prior art has never attempted to use energy CT equipment for collagen content determination, no calibration phantom has ever been specifically designed as this invention to contain multiple collagen-pure substance component material bodies with different collagen contents for each pure substance component. This phantom can be conveniently used with various energy CT devices to calibrate the correspondence between the collagen scan content and the actual collagen content of various pure substance component + collagen combinations corresponding to that energy CT device to a state as close as possible to the actual value.

[0076] Optionally, the calibration component of the present invention can also be a mixed solution of collagen and pure substance components. In the absence of a phantom, for a specific combination of pure substance component (hereinafter referred to as "pure substance component Z") and collagen, multiple sets of mixed solutions of collagen and pure substance component Z with different collagen contents can be prepared, and these multiple sets of mixed solutions of collagen and pure substance component Z can be scanned using an energy CT scanner to obtain the correspondence between the collagen scan content and the actual collagen content of the pure substance component Z + collagen combination corresponding to the energy CT scanner.

[0077] The above-described phantom embodiments are equivalent to solid-state calibration devices, and the above-described embodiments of the collagen-pure substance component mixture solution are equivalent to liquid-state calibration devices. However, it is understood that the calibration devices of the present invention are not limited to the two embodiments described above. Any entity comprising a mixture of multiple sets of collagen-pure substance components (each pure substance component includes one pure substance, and for each pure substance component there are at least two sets of collagen-pure substance components with different collagen contents) and whose collagen scan content versus actual collagen content can be obtained by energy-sensitive CT scanning can serve as the calibration device of the present invention. Furthermore, when using the phantom calibration device for calibration, energy-sensitive CT scanning data from only certain regions can be used as needed to obtain a collagen scan content versus actual collagen content correspondence sufficient to fit the desired pure substance component-collagen combination that meets the accuracy requirements. Similarly, when calibrating using a calibrator for a mixed solution of collagen-pure components, energy CT scan data from only a few groups of the mixed solutions of collagen-pure components can be used as needed to obtain a correlation between the collagen scan content and the actual collagen content of the desired pure component-collagen combination that meets the accuracy requirements.

[0078] Figures 5-7 The regression line relationship between the collagen scan content obtained by measuring the collagen-calcium chloride mixed solution using the collagen content measurement method of the present invention under different scanning conditions and the actual collagen content (actual collagen content) of the collagen-calcium chloride mixed solution was compared. The collagen and calcium chloride contents in the collagen-calcium chloride mixed solution are shown in Table 3 below.

[0079]

[0080] When measuring the collagen content of a collagen-calcium chloride mixed solution using the collagen content measurement method of the present invention, the above 24 groups of collagen-calcium chloride mixed solutions were scanned under different scanning conditions as shown in Table 4 below using the same dual-energy CT device (tube voltage 80 / 140kV, energy scanning mode).

[0081]

[0082] Figures 5-7 The data shows no significant difference in the slope of the curves under different scanning parameters (pitch, tube current) and different CaCl2 concentrations. Figure 5For comparisons under different pitches ((A) CaCl2 concentration of 10 mg / ml, tube current of 230 mA; (B) CaCl2 concentration of 10 mg / ml, tube current of 315 mA; (C) CaCl2 concentration of 10 mg / ml, tube current of 400 mA; (D) CaCl2 concentration of 20 mg / ml, tube current of 230 mA; (E) CaCl2 concentration of 20 mg / ml, tube current of 315 mA; (F) CaCl2 concentration of 20 mg / ml, tube current of 400 mA; (G) CaCl2 concentration of 40 mg / ml, tube current of 230 mA; (H) CaCl2 concentration of 40 mg / ml, tube current of 315 mA; (I) CaCl2 concentration of 40 mg / ml, tube current of 400 mA), Figure 6 For comparison under different tube currents ((A) CaCl2 concentration of 10 mg / ml, pitch of 0.984:1; (B) CaCl2 concentration of 10 mg / ml, pitch of 0.516:1; (C) CaCl2 concentration of 20 mg / ml, pitch of 0.984:1; (D) CaCl2 concentration of 20 mg / ml, pitch of 0.516:1; (E) CaCl2 concentration of 40 mg / ml, pitch of 0.984:1; (F) CaCl2 concentration of 40 mg / ml, pitch of 0.516:1), Figure 7 For comparisons under different CaCl2 concentrations ((A) tube current 230mA, pitch 0.984:1; (B) tube current 315mA, pitch 0.984:1; (C) tube current 400mA, pitch 0.984:1; (D) tube current 230mA, pitch 0.516:1; (E) tube current 315mA, pitch 0.516:1; (F) tube current 400mA, pitch 0.516:1), the hypothesis H0 was that the slopes of the regression lines were equal under all these different scanning conditions. The calculated p-values ​​were all greater than 0.05. Therefore, it can be concluded that the above hypothesis H0 cannot be rejected. Thus, it can be considered that the slopes of the regression lines under different scanning parameters (pitch, tube current) and different CaCl2 concentrations are not significantly different and are consistent; the regression lines are nearly parallel, indicating that the collagen content measurement method of this invention has extremely high measurement accuracy and stability.

[0083] Table 5 below shows the consistency test results of two researchers using the collagen content measurement method of the present invention to determine collagen content. The ICC range is 0.990~1.000 (ICC is the class correlation coefficient, used to assess the consistency of measurements; ICC < 0.4 is considered poor consistency, ICC 0.4-0.75 is considered good consistency, and ICC ≥ 0.75 is considered excellent consistency). Table 6 below shows the consistency test results of the same researcher using the collagen content measurement method of the present invention to determine collagen content twice. The ICC range is 0.993~0.999. The above experiments demonstrate that the collagen content measurement method of the present invention has good repeatability and stability.

[0084]

[0085]

[0086] Thanks to the inventors filling the long-standing gap in the industry regarding the determination of collagen characteristic parameters, the collagen content measurement method of this invention achieves, for the first time, the determination of collagen content in mixtures containing collagen and other purified substances using energy-sensitive CT (ESCT) equipment. Furthermore, based on the inventors' groundbreaking discovery of the approximately linear relationship between the scanned collagen content and the actual collagen content obtained from ECT scan data, the collagen content measurement method of this invention can further improve the accuracy of the measured collagen content. By scanning the calibration piece of this invention with a current ECT device to obtain the correspondence between the scanned collagen content and the actual collagen content corresponding to collagen + a certain purified substance, the collagen content of any object containing collagen + the stated purified substance can be conveniently and accurately measured using this ECT equipment. Compared to other existing methods for collagen content determination, this invention undoubtedly represents a qualitative leap in many aspects, including measurement accuracy, measurement efficiency, cost-effectiveness, and applicability.

[0087] In particular, in clinical testing, the human body contains more than just collagen; for example, tendons contain calcium, and the liver contains iron. The presence of these other elements can affect the accuracy of collagen content measurement. The collagen content measurement method of this invention can accurately separate collagen from other elements in energy-sensitive CT scan data, thereby measuring a highly accurate collagen content. This invention effectively meets the clinical need for collagen content measurement in various parts of the human body, especially by providing non-invasive collagen content measurement, offering reliable data for subsequent clinical decisions regarding physiological repair and disease prevention, and possessing extremely high clinical application value.

[0088] According to embodiments of the present invention, a computer-readable storage medium is also provided, on which encoded instructions are recorded, which, when executed, implement the method for measuring collagen content described above. The computer-readable storage medium may include hard disk drives, floppy disk drives, optical disc read / write (CD-R / W) drives, digital universal disk (DVD) drives, flash memory drives, and / or solid-state storage devices, etc.

[0089] According to embodiments of the present invention, a computer program product is also provided, comprising a computer program that, when executed, implements the method for measuring collagen content according to the present invention. The computer program product can be implemented using various programming languages, such as C, C++, Java, Python, JavaScript, etc., to adapt to different development environments and platform requirements.

[0090] According to an embodiment of the present invention, a system for measuring collagen content is also provided.

[0091] Figure 8 A schematic block diagram of a system 800 for measuring collagen content according to an embodiment of the present invention is shown. Figure 8 As shown, the system 800 may include an energy CT device 820 and a computing unit 840.

[0092] The energy CT device 820 can be configured to perform energy scanning on a measurement object containing collagen to obtain CT scan data of the measurement object.

[0093] The computing unit 840 can be configured to extract the collagen content of the measured object from the CT scan data of the measured object based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object.

[0094] Alternatively, the computing unit 840 can determine its characteristic parameters by simulating collagen as a chemical formula.

[0095] Alternatively, the simulated chemical formula can be any of the following: C M ; C 5M H 9M N M O 3M ; C 6M H 14M N 2M O 3M ; C 169858M H 990099M N 29979M O 403125M Na870M P 323M S 624M Cl 846M K 256M ;or C 82431M H 950495M N 15703M O 465000M Na 2175M P 7104M S 2807M Cl 846M , Where M > 0.

[0096] Optionally, the characteristic parameters of the collagen have corresponding ranges under different energy voltages: [characteristic parameters] min , Feature parameters max ], where 0 < feature parameter min <1, 0 < Feature parameters max <1, characteristic parameters min < Feature parameters max Furthermore, as the energy voltage increases, the characteristic parameters... min and the feature parameters max They are all monotonically decreasing.

[0097] Optionally, when the energy voltage is in the range of 40keV to 140keV, the characteristic parameters... min The characteristic parameter is within the range of 0.20750 to 0.13740. max It falls within the range of 0.28324 to 0.15214.

[0098] Optionally, the energy CT device 820 may be further configured to: perform energy scanning on the calibration element 200 of the present invention to obtain CT scan data of at least two sets of collagen-pure substance mixtures with different collagen contents for pure substances that may be contained in the measured object. Furthermore, the calculation unit 840 may be further configured to: extract collagen scan content from the at least two sets of CT scan data based on characteristic parameters of collagen and characteristic parameters of pure substances that may be contained in the measured object; obtain a correspondence between collagen scan content and actual collagen content based on the extracted collagen scan content and the actual collagen content of each of the at least two sets of collagen-pure substance mixtures; and obtain the actual collagen content in the measured object based on the extracted collagen scan content and the correspondence between collagen scan content and actual collagen content.

[0099] Optionally, the correspondence between the scanned collagen content and the actual collagen content is: y = kx + b, where y is the actual collagen content and x is the scanned collagen content.

[0100] The system described above for measuring collagen content can implement the method for measuring collagen content according to the present invention as described above. Many of the design concepts and details applicable to the method for measuring collagen content of the present invention are also applicable to the system described above for measuring collagen content, and the same beneficial technical effects can be obtained, which will not be repeated here.

[0101] The various aspects of the present invention have been described above through exemplary embodiments. However, it should be understood that various modifications can be made to the above exemplary embodiments without departing from the spirit and scope of the invention. For example, if suitable results can be achieved if the described techniques are performed in a different order and / or if components in the described system, architecture, device, or circuit are combined in different ways and / or replaced or supplemented by other components or their equivalents, then correspondingly, these modified other embodiments also fall within the scope of protection of the claims.

Claims

1. A calibration piece for calibrating collagen content determination, comprising a mixture of multiple collagen-pure substance components, each pure substance component comprising one pure substance, and for each pure substance component comprising at least two mixtures of collagen-pure substance components with different collagen contents. When the calibration piece is scanned by an energy CT device, at least two sets of CT scan data are obtained for at least two sets of collagen-pure substance mixtures with the same pure substance composition. Based on the characteristic parameters of collagen and the characteristic parameters of the pure substances in the pure substance composition, the collagen scanning content is extracted from the at least two sets of CT scan data respectively. Based on the extracted collagen scanning content and the collagen content of each of the at least two sets of collagen-pure substance mixtures, the correspondence between the collagen scanning content and the actual collagen content is obtained.

2. The calibration component as described in claim 1, characterized in that, The calibration component comprises a phantom and a mixed solution of collagen-pure components.

3. The calibration component as described in claim 2, characterized in that, The phantom includes multiple regions, each region having a material body of a collagen-pure substance component. Each pure substance component includes a pure substance, and for each pure substance component, there are at least two sets of collagen-pure substance material bodies with different collagen contents.

4. A method for measuring collagen content, comprising the following steps: a) Performing an energy scan on a collagen-containing object using an energy CT scanner to obtain CT scan data of the object; and b) Extract the collagen content of the measured object from the CT scan data of the measured object based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object.

5. The method as described in claim 4, characterized in that, The characteristic parameters of collagen were determined by simulating its chemical formula.

6. The method as described in claim 5, characterized in that, The chemical formula is any of the following: C M ; C 5M H 9M N M O 3M ; C 6M H 14M N 2M O 3M ; C 169858M H 990099M N 29979M O 403125M Na 870M P 323M S 624M Cl 846M K 256M ; or C 82431M H 950495M N 15703M O 465000M Na 2175M P 7104M S 2807M Cl 846M , Where M > 0.

7. The method as described in claim 4, characterized in that, The characteristic parameters of the collagen have corresponding ranges under different energy voltages: [characteristic parameters] min , Feature parameters max ], Where 0 < characteristic parameter min <1, 0 < Feature parameters max <1, characteristic parameters min Feature parameters max , As the energy voltage increases, the characteristic parameters min and the feature parameters max They are all monotonically decreasing.

8. The method as described in claim 7, characterized in that, When the energy voltage is in the range of 40keV to 140keV, the characteristic parameters min The characteristic parameter is within the range of 0.20750 to 0.13740. max It falls within the range of 0.28324 to 0.15214.

9. The method of any one of claims 4-8, further comprising the following steps: c) Perform energy scanning on the calibrator as described in any one of claims 1-3 using the energy CT device to obtain CT scan data of at least two sets of collagen-pure substance mixtures with different collagen contents for pure substances that may be contained in the measured object; d) Extract the collagen scan content from the at least two sets of CT scan data based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object; e) Based on the extracted collagen scan content and the collagen content of each of the at least two groups of collagen-pure component mixtures, obtain the correspondence between collagen scan content and actual collagen content; and f) Based on the collagen scan content of the measured object extracted in step b), the correspondence between the collagen scan content and the actual collagen content is obtained to obtain the actual collagen content in the measured object.

10. The method as described in claim 9, characterized in that, The correspondence between the scanned collagen content and the actual collagen content is: y = kx + b, where y is the actual collagen content and x is the scanned collagen content.

11. A system for measuring collagen content, comprising: An energy CT device is configured to perform energy scanning on a measurement object containing collagen to obtain CT scan data of the measurement object; as well as The calculation unit is configured to extract the collagen content of the measured object from the CT scan data of the measured object based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object.

12. The system as claimed in claim 11, characterized in that, The computational unit determines the characteristic parameters of collagen by simulating it as a chemical formula.

13. The system as described in claim 12, characterized in that, The chemical formula is any of the following: C M ; C 5M H 9M N M O 3M ; C 6M H 14M N 2M O 3M ; C 169858M H 990099M N 29979M O 403125M Na 870M P 323M S 624M Cl 846M K 256M ; or C 82431M H 950495M N 15703M O 465000M Na 2175M P 7104M S 2807M Cl 846M , Where M > 0.

14. The system as claimed in claim 11, characterized in that, The characteristic parameters of the collagen have corresponding ranges under different energy voltages: [characteristic parameters] min , Feature parameters max ], Where 0 < characteristic parameter min <1, 0 < Feature parameters max <1, characteristic parameters min Feature parameters max , As the energy voltage increases, the characteristic parameters min and the feature parameters max They are all monotonically decreasing.

15. The system as described in claim 14, characterized in that, When the energy voltage is in the range of 40keV to 140keV, the characteristic parameters min The characteristic parameter is within the range of 0.20750 to 0.13740. max It falls within the range of 0.28324 to 0.15214.

16. The system as claimed in any one of claims 11-15, characterized in that, The energy CT device is further configured as follows: Energy scanning is performed on the calibrator as described in any one of claims 1-3 to obtain CT scan data of at least two sets of collagen-pure substance mixtures with different collagen contents for pure substances that may be contained in the measured object; and The computing unit is further configured as follows: Collagen scan content was extracted from the at least two sets of CT scan data based on the characteristic parameters of collagen and the characteristic parameters of pure substances that may be contained in the measured object. Based on the extracted collagen scan content and the collagen content of each of the at least two groups of collagen-pure component mixtures, a correspondence between collagen scan content and actual collagen content is obtained; and The actual collagen content in the measured object is obtained based on the extracted collagen scan content and the correspondence between the collagen scan content and the actual collagen content.

17. The system as claimed in claim 16, characterized in that, The correspondence between the scanned collagen content and the actual collagen content is: y = kx + b, where y is the actual collagen content and x is the scanned collagen content.

18. A computer-readable storage medium having encoded instructions recorded thereon, which, when executed, implement the method as described in any one of claims 4-10.

19. A computer program product comprising a computer program that, when executed, implements the method as described in any one of claims 4-10.

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