Patent Publication Number: US-2021186337-A1

Title: Internal body temperature measurement device and internal body temperature measurement method

Description:
CROSS-REFERENCE TO RELATED APPLICATIONS 
     This application is a national phase entry of PCT Application No. PCT/JP2019/022568, filed on Jun. 6, 2019, which claims priority to Japanese Application No. 2018-121861, filed on Jun. 27, 2018, which applications are hereby incorporated herein by reference. 
    
    
     TECHNICAL FIELD 
     The present invention relates to an in-vivo temperature measurement device and an in-vivo temperature measurement method for measuring a core temperature of a living body. 
     BACKGROUND 
     In recent years, social jet-lag has been a problem. This is a problem that causes various physical and mental disorders due to the disagreement between the social time and the circadian time or the circadian system of each person who live a life and leads to lifestyle-related diseases. The circadian time can be known from various endocrine substances or vital information. The endocrine substances require several hours for measurement and cause both mental and physical loads. 
     In a living body, a temperature region not being affected by a change in outside-air temperature exists in a part located beyond a certain depth between the epidermis and a core (hereinafter, the temperature of such a part being referred to as “core temperature”). It is known that measurement of changes in core temperature as vital information is useful for grasping the circadian system. 
     The temperature of the core is measured by a method of inserting a probe of a thermometer into the body or swallowing the thermometer, but it can be said that such a method is not good in terms of hygiene and causes a large physical and mental burden. Therefore, a non-invasive method from outside of the body is required for measurement, and it can be said that a percutaneous temperature measurement method is particularly useful for easy and daily body temperature management (for example, see Non-Patent Literature 2). 
     Conventionally, a percutaneous thermometer has been used to measure the body temperature under the armpit or in the oral cavity, but it cannot be always said to reflect the core temperature for the following reasons. The reason is that it takes a time for the temperature to be transmitted from the core to the skin because thermal capacity and thermal resistance of the subcutaneous tissue change due to the amount of a blood flowing in the capillaries. Further, since the percutaneously measured temperatures are different from each other, the core temperature may not be reflected. 
     Therefore, there has been proposed a method of correcting the core temperature taking into consideration the time taken for the temperature to be transmitted from the core to the skin. However, a formula is established in such a method assuming that the temperature is in a sufficiently stable thermal equilibrium state, resulting in a cause of error in measuring the core temperature which changes every moment. Since the outside-air temperature, the deep body temperature, and the thermal resistance of the subcutaneous tissue change with time, it can be said that the living body is always in a non-thermal equilibrium state. Therefore, accuracy may be insufficient in the estimation of the core temperature using the conventional estimation model. 
     Citation List 
     Non-Patent Literature 
     
         
         Non-Patent Literature 1: Akio Nakayama, “New Physiology System Volume 22”, Igaku-Shoin Ltd. (1987) 
         Non-Patent Literature 2: Shinya Nakagawa et al., “Wearable Core Temperature Thermometer implemented by the MEMS Heat Flux Sensor”, Transactions E of The Institute of Electrical Engineers of Japan, Volume 135 (2015), No. 8, p. 343-348. 
       
    
     SUMMARY 
     Technical Problem 
     Embodiments of the present invention have been made to solve the above-described problems, and an object thereof is to provide an in-vivo temperature measurement device capable of more accurately estimating a core temperature that changes every moment. 
     Means for Solving the Problem 
     In order to solve the above-described problems, an in-vivo temperature measurement device according to embodiments of the present invention includes: a plurality of thermal resistors; first temperature sensors and second temperature sensors provided at both ends of the thermal resistors, respectively; a storage unit that stores an estimation model of a core temperature of a living body that takes into consideration a non-thermal equilibrium state of the living body, and thermal resistance values of the thermal resistors; and an arithmetic circuit that, based on a plurality of temperatures measured by the first temperature sensors and the second temperature sensors, estimates the core temperature of the living body using the estimation model and the thermal resistance values of the thermal resistors, wherein the first temperature sensors are provided on the thermal resistors to be closer to the living body and measures a first temperature indicating an epidermis temperature of the living body, the second temperature sensors are provided on the thermal resistors to be opposite to the living body and measure a second temperature at a position away from the living body, and the thermal resistance values of the plurality of thermal resistors are different from one another. 
     In the in-vivo temperature measurement device according to embodiments of the present invention, the arithmetic circuit may include: a time count unit that counts measurement times at which the first temperature sensors and the second temperature sensors measure the plurality of temperatures; and an estimation unit that, based on the plurality of temperatures measured by the first temperature sensors and the second temperature sensors at the measurement times, estimates the core temperature of the living body using the estimation model and the thermal resistance values of the thermal resistors, and the arithmetic circuit may generate time-series data in which the measurement time and the core temperature estimated by the estimation unit are associated with each other. 
     In the in-vivo temperature measurement device according to embodiments of the present invention, the number of the plurality of thermal resistors may be at least three. 
     In the in-vivo temperature measurement device according to embodiments of the present invention, the estimation model may be represented by a following expression: 
     
       
         
           
             
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     wherein, TC indicates the core temperature at the measurement time t, RSi (i=1, 2, 3) indicates the thermal resistance values of the thermal resistors, TSi indicates the first temperatures measured by the first temperature sensors, Ti=(TSi(t)−TUi(t)), (TUi indicates the second temperatures measured by the second temperature sensors), and TSi′=dTSi(t)/dt. 
     An in-vivo temperature measurement method according to embodiments of the present invention includes: a temperature measurement step of measuring a plurality of temperatures with first temperature sensors and second temperature sensors provided at both ends of a plurality of thermal resistors, respectively; and an arithmetic step of estimating, using an estimation model of a core temperature that takes into consideration a non-thermal equilibrium state of a living body stored in a storage unit, and thermal resistance values of the thermal resistors, the core temperature of the living body based on the plurality of temperatures measured in the temperature measurement step, wherein the first temperature sensors are provided on the thermal resistors to be closer to the living body and measures a first temperature indicating an epidermis temperature of the living body, the second temperature sensors are provided on the thermal resistors to be opposite to the living body and measure a second temperature at a position away from the living body, and the thermal resistance values of the plurality of thermal resistors are different from one another. 
     Effects of Embodiments of the Invention 
     According to embodiments of the present invention, based on a plurality of temperatures measured by a plurality of temperature sensors provided at both ends of a plurality of thermal resistors, respectively, a core temperature of a living body is estimated using an estimation model of the core temperature that takes into consideration a non-thermal equilibrium state in the living body. Accordingly, it is possible to more accurately estimate the core temperature that changes every moment. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG. 1  is a diagram schematically illustrating a temperature distribution of subcutaneous tissue of a living body. 
         FIG. 2  is a diagram showing a thermal model of human body for explaining a principle of embodiments of the present invention. 
         FIG. 3  is a diagram showing an equivalent circuit of  FIG. 2 . 
         FIG. 4  is a diagram showing a thermal model of human body for explaining a principle of embodiments of the present invention. 
         FIG. 5  is a diagram showing an equivalent circuit of  FIG. 4 . 
         FIG. 6  is a block diagram showing a configuration of an in-vivo temperature measurement device according to an embodiment of the present invention. 
         FIG. 7  is a block diagram showing the configuration of the in-vivo temperature measurement device according to the embodiment of the present invention. 
         FIG. 8  is a flowchart for explaining an operation of the in-vivo temperature measurement device according to the embodiment of the present invention. 
         FIG. 9A  is a diagram for explaining measurement of a core temperature with the in-vivo temperature measurement device according to the embodiment of the present invention. 
         FIG. 9B  is a diagram illustrating a result measured by the in-vivo temperature measurement device according to the embodiment of the present invention. 
     
    
    
     DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS 
     A preferred embodiment of the present invention will be described in detail below with reference to  FIGS. 1 to 9B . 
     Principle of Embodiments of Invention 
     First, a principle of the an in-vivo temperature measurement device according to embodiments of the present invention will be described with reference to  FIGS. 1 to 5 . 
       FIG. 1  is a diagram schematically illustrating a temperature distribution of subcutaneous tissue of a living body. As shown in  FIG. 1 , a region of a core temperature exists in a part of the living body located beyond a certain depth in a depth direction from the epidermis to the subcutaneous tissue, the core temperature not being affected by a change in outside-air temperature. A temperature in such a region is measured as a core temperature T C . Usually, an epidermis temperature T S  is lower than the core temperature T C , and a temperature gradient occurs from the core to the epidermis. 
       FIG. 2  is a diagram showing a thermal model of human body (AA′B′B). The thermal model of human body includes a region from the region where the core of the living body is located to the outside air. Specifically, the thermal model of human body shown in  FIG. 2  indicates the core where a heat source of the living body exists, the subcutaneous tissue of the living body, a heat insulating material (thermal resistor) existing in contact with the outside of the living body, a temperature at each part up to the outside air of the heat insulating material, a thermal resistance, and a thermal capacity. 
     A temperature in the core region of the living body, in which the heat source exists, is represented by the core temperature T C . A temperature passing through the subcutaneous tissue from the heat source is represented by the epidermis temperature T S . The subcutaneous tissue includes a thermal resistance R B  and a thermal capacity C B . Further, a temperature passing through the heat insulating material provided outside in contact with the epidermis of the living body is represented by an upper surface temperature T U . The heat insulating material includes the thermal resistance R S  and the thermal capacity C S . In addition, a temperature in air is represented by an air temperature T A . 
       FIG. 3  is an equivalent circuit in which the thermal model of human body shown in  FIG. 2  is depicted as an RC series circuit. As shown in  FIG. 3 , in a technique for measuring the core temperature T C  of a conventional example, the core temperature T C  is derived from the epidermis temperature T S  and the upper surface temperature T U  when respective capacitors in the equivalent circuit are fully charged and enter a steady state (for example, see Non-Patent Literature 2). From the thermal resistance R B  of the subcutaneous tissue, the thermal resistance R S  of the heat insulating material (thermal resistor), the epidermis temperature T S , and the upper surface temperature T U , the core temperature T C  can be calculated using Expression (1) below. 
     
       
         
           
             
               
                 
                   
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     Using two thermal resistance values, for example, a thermal resistance value RSi of a first thermal resistor and a thermal resistance value R S2  of a second thermal resistor as known thermal resistance R S  of the heat insulating material in Expression (1) described above, two expressions are created to cancel out the unknown thermal resistance R B  of the subcutaneous tissue. However, as described above, the thermal resistance R B  of the subcutaneous tissue, the thermal resistance R S  of the heat insulating material, the epidermis temperature T S , the upper surface temperature T U , and the core temperature T C  are actually not in a steady state. Therefore, it is considered that each of the values changes with time, and a new estimation model is constructed. 
       FIGS. 4 and 5  are diagrams showing a newly constructed thermal model of human body and an equivalent circuit thereof. 
     As shown in  FIGS. 4 and 5 , a voltage V CB (t) applied to a thermal capacity C B (t) of the subcutaneous tissue is expressed by Expression (2) below. Further, Expression (2) is modified to derive Expression (3) indicating a core temperature T C (t). 
     
       
         
           
             
               
                 
                   
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     Using three thermal resistance values different from one another, for example, a thermal resistance value R S1  of a first thermal resistor, a thermal resistance value R S2  of a second thermal resistor, and a thermal resistance value R S3  of a third thermal resistor as known thermal resistance R S  of the heat insulating material in Expression (3) described above, three expressions are created to cancel out the unknown thermal resistance R B (t) of the subcutaneous tissue and the thermal capacity C B (t) of the subcutaneous tissue. 
     More specifically, using Expression (3) described above, a determinant indicated by Expression (4) below is created using an epidermis temperature T S1 (t) and an upper surface temperature T U1 (t) in the first thermal resistor (R S1 ), an epidermis temperature T S2 (t) and an upper surface temperature T U2 (t) in the second thermal resistor (R S2 ), and an epidermis temperature T S3 (t) and an upper surface temperature T U3 (t) in the third thermal resistor (R S3 ). 
     
       
         
           
             
               
                 
                   
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     Solving Expression (4) described above, the core temperature T C (t) is expressed by Expression (5) below. Here, Expression (5) satisfies following conditions: T i =(T Si (t)−T Ui (t)), T Si ′=dT Si (t)/dt, (i=1, 2, 3). 
     
       
         
           
             
               
                 
                   
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     As described above, the in-vivo temperature measurement device according to embodiments of the present invention is configured to measure the epidermis temperatures T S1  to T S3  and the upper surface temperatures T U1  to T U3  measured by the thermal resistors (thermal resistance values R S1  to R S3 ) and to obtain an estimation value of the core temperature T C  by applying the measured temperatures to Expression (5) which is the newly constructed estimation model of the core temperature T C . 
     Embodiment 
     An in-vivo temperature measurement device  1  according to embodiments of the present invention will be described in detail below. 
       FIGS. 7 and 8  are block diagrams showing a configuration of the in-vivo temperature measurement device  1  according to the present embodiment. The in-vivo temperature measurement device  1  includes, on a sheet-shaped base  15 , a core temperature measurement instrument  10 , an arithmetic circuit  11 , a memory  12 , a communication circuit  13  functioning as an I/F circuit with the outside, and a battery  14  for supplying power to the arithmetic circuit  11  and the communication circuit  13 . 
     The core temperature measurement instrument  10  includes three heat flux sensors  101 ,  102 , and  103 . The heat flux sensors  101 ,  102 , and  103  are devices that measure heat transfer per unit time or per unit area. 
     The heat flux sensors  101 ,  102 , and  103  include thermal resistors  101   r ,  102   r ,  103   r , and temperature sensors (second temperature sensors)  101   u ,  102   u , and  103   u  and temperature sensors (first temperature sensors)  101   s ,  102   s , and  103   s  which are provided at both ends of the thermal resistors  101   r ,  102   r , and  103   r , respectively. 
     The thermal resistors  101   r ,  102   r , and  103   r  provided in the heat flux sensors  101 ,  102 , and  103 , respectively, are made of heat insulating materials having different thickness and materials and have different thermal resistance values R S1 , R S2 , and R S3 , respectively. 
     The temperature sensors  101   s ,  102   s , and  103   s  are provided on the thermal resistors  101   r ,  102   r , and  103   r  to be closer to a living body  2 , respectively, and measure the epidermis temperature T S  (first temperature) of the living body  2 . 
     The temperature sensors  101   u ,  102   u , and  103   u  are provided on the thermal resistors  101   r ,  102   r , and  103   r  to be opposite to the living body  2 , respectively, and measure the upper surface temperature T U  (second temperature) at a position away from the living body  2 . 
     As the temperature sensors  101   s  to  103   s  and  101   u  to  103   u , for example, a known thermistor or a thermopile using a thermocouple can be used. 
     The arithmetic circuit  11  includes a time count unit  11   o  and an estimation unit  11 . The arithmetic circuit  11  estimates the core temperature T C (t) of the living body  2  based on the epidermis temperature T S (t) measured by the temperature sensors  101   s  to  103   s  and the upper surface temperature T U (t) measured by the temperature sensors  101   u  to  103   u . More specifically, the estimation unit  111  estimates the core temperature T C  by substituting the epidermis temperatures T S1 , T S2 , and T S3  measured by the temperature sensors  101   s  to  103   s  and the upper surface temperatures T U1 , T U2 , and T U3  measured by the temperature sensors  101   u  to  103   u  at a measurement time t of the time count unit  110  into Expression (5) representing the estimation model described above. 
     The arithmetic circuit  11  generates and outputs time-series data of the estimated core temperature T C  of the living body  2 . The time-series data is data in which the measurement time and the estimated core temperature T C  are associated with each other. 
     The memory  12  stores information on the estimation model (Expression (5)) of the core temperature T C  which is constructed in advance. In addition, the memory  12  also stores the thermal resistance values R S1 , R S2 , and R S3  of the heat flux sensors  101 ,  102 , and  103 . The memory  12  can be realized by a predetermined storage region in a rewritable nonvolatile storage device (for example, a flash memory) provided in the in-vivo temperature measurement device  1 . 
     The communication circuit  13  outputs the time-series data of the core temperature T C  of the living body  2  generated by the arithmetic circuit  11  to the outside. Such a communication circuit  13  is an output circuit to which an USB or other cables can be connected when outputting data or the like in a wired manner, but, for example, a wireless communication circuit compliant with Bluetooth (registered trademark) may be used. 
     The sheet-shaped base  15  functions as a base on which the core temperature measurement instrument  10 , the arithmetic circuit  11 , the memory  12 , the communication circuit  13 , and the battery  14  are mounted, and also includes wirings through which these elements are electrically connected to each other. Considering that the in-vivo temperature measurement device  1  is connected onto the epidermis of the living body, a deformable flexible substrate is desirably used for the sheet-shaped base  15 . 
     Further, an opening is provided in a part of the sheet-shaped base  15 , and the heat flux sensors  101 ,  102 , and  103  are mounted on the base  15  so as to contact with the epidermis of the living body  2  through the opening. 
     Here, the in-vivo temperature measurement device  1  is realized by a computer. Specifically, the arithmetic circuit  11  is realized in a manner that a processor such as a CPU or a DSP executes various data processing according to a program stored in a storage device including the memory  12  such as a ROM, a RAM, and a flash memory provided in the in-vivo temperature measurement device  1 . The program for causing the computer to function as the in-vivo temperature measurement device  1  can be recorded in a recording medium or can also be provided through a network. 
     Operation of In-vivo Temperature Measurement Device 
     An operation of the in-vivo temperature measurement device  1  including the above-described configuration will be described below with reference to a flowchart of  FIG. 8 . The memory  12  stores, in advance, the estimation model (Expression (5)) of the core temperature T C  and the thermal resistance values R S1 , R S2 , and R S3  of the thermal resistors  101   r ,  102   r , and  103   r  of the respective heat flux sensors  101 ,  102 , and  103 . 
     Further, the base  15  of the in-vivo temperature measurement device  1  is disposed in contact with the epidermis of the living body  2  in advance. 
     First, the arithmetic circuit  11  reads, from the memory  12 , the estimation model (Expression (5)) of the core temperature T C  and the thermal resistance values R S1 , R S2 , and R S3  of the thermal resistors  101   r ,  102   r , and  103   r  included in the respective heat flux sensors  101 ,  102 , and  103  (step S 1 ). The arithmetic circuit  11  sets the read thermal resistance values R S1 , R S2 , and R S3  in the estimation model (Expression (5)). 
     Next, the temperature sensors  101   s  to  103   s  and  101   u  to  103   u  of the heat flux sensors  101 ,  102 , and  103  measure the epidermis temperatures T S1 , T S2 , and T S3  and the upper surface temperatures T U1 , T U2 , and T U3  (step S 2 ). The measured epidermis temperatures T S1 , T S2 , and T S3  and the upper surface temperatures T U1 , T U2 , and T U3  are sent to the arithmetic circuit  11 . 
     Then, the estimation unit  11  substitutes the epidermis temperatures T S1 , T S2 , and T S3  and the upper surface temperatures T U1 , T U2 , and T U3  measured in step S 2  into the estimation model of the above-described Expression (5) to estimate the core temperature T C  (step S 3 ). The estimated value of the core temperature T C  of the living body  2  is stored in the memory  12 . 
     Next, the arithmetic circuit  11  generates time-series data of the estimated core temperature T C  (step S 4 ). More specifically, the arithmetic circuit  11  repeatedly executes steps S 2  and S 3  to generate time-series data of the core temperature T C . The generated time-series data of the core temperature T C  is stored in the memory  12 . 
     Then, the arithmetic circuit  11  outputs the generated time-series data of the core temperature T C  to the outside through the communication circuit  13  (step S 5 ). For example, the time-series data of the core temperature T C  is displayed on a display screen of a smartphone or a tablet terminal via a communication network (not shown). 
     Measurement Result of In-Vivo Temperature Measurement Device 
     A result of the core temperature T C  measured by the in-vivo temperature measurement device  1  according to the present embodiment will be described below with reference to  FIGS. 9A and 9B . 
     As shown in  FIG. 9A , in the measurement of the core temperature T C  by the in-vivo temperature measurement device  1 , a reference temperature sensor T S  for measuring a reference temperature of the core as a heat source is used for comparison. Further, according to the conventional example for comparison, the core temperature T C  is measured based on the estimation model (for example,  FIGS. 2 and 3 ) in which only a thermal equilibrium state is defined. 
     Both the in-vivo temperature measurement device  1  of the present embodiment and the in-vivo temperature measurement device of the conventional example are installed on the surface of the skin phantom under the same conditions and measure the temperature. In  FIG. 9A , only the core temperature measurement instrument  10  of the in-vivo temperature measurement device  1  is schematically shown. 
       FIG. 9B  shows measurement results. In  FIG. 9B , a horizontal axis represents a measurement time (minute), and a vertical axis represents a core temperature T C  (° C.). As can be seen from  FIG. 9B , a measurement result “c” according to the conventional example has a large error with respect to a reference core temperature “r”. On the other hand, it can be seen that a measurement result “p” by the in-vivo temperature measurement device  1  of the present embodiment has a small error with respect to the reference core temperature “r”. 
     As described above, the in-vivo temperature measurement device  1  according to the present embodiment uses the estimation model in consideration with the non-thermal equilibrium state in the living body  2  to estimate the core temperature T C  using the epidermis temperatures T S1 , T S2 , and T S3  and the upper surface temperatures T U1 , T U2 , and T U3  measured by the temperature sensors  101   s  to  103   s  and  101   u  to  103   u . Therefore, it is possible to improve the measurement accuracy compared with the core temperature T C  estimated by the conventional estimation model in which only the thermal equilibrium state is defined, and to more accurately estimate the core temperature that changes every moment. 
     As a result, it is possible to evaluate physical and mental disorders due to social jet-lag, for example, to grasp the consistency or inconsistency between the time of sleep or wake-up and the biological rhythm of an individual. 
     In the embodiment described above, a case has been described in which the core temperature measurement instrument  10  and the arithmetic circuit  11  are configured in the same casing, but the arithmetic circuit  11  may be configured independently of the core temperature measurement instrument  10 . For example, the arithmetic circuit  11  may be configured to transmit the respective temperatures measured by the core temperature measurement instrument  10  to terminals, for example, a server device, PC, and a smartphone, through a communication network, and to perform an arithmetic process. 
     Although the embodiment of the in-vivo temperature measurement device and the in-vivo temperature measurement method of embodiments of the present invention has been described above, the present invention is not limited to the embodiment described above, and various modifications that can be envisioned by those skilled in the art can be made within the scope of the invention described in the claims. 
     REFERENCE SIGNS LIST 
     
         
         
           
               1  In-vivo temperature measurement device 
               2  Living body 
               10  Core temperature measurement instrument 
               11  Arithmetic circuit 
               12  Memory 
               13  Communication circuit 
               14  Battery 
               15  Base 
               101 ,  102 ,  103  Heat flux sensor 
               101   u ,  102   u ,  103   u ,  101   s ,  102   s ,  103   s  Temperature sensor 
               110  Time count unit 
               111  Estimation unit.