The present invention relates to an apparatus for measuring biological light which non-invasively supports diagnosis of disorder.
An apparatus for measuring biological light is capable of non-invasively measuring local changes in hemoglobin in a living organism. This is a method of measuring a changing amount of hemoglobin by irradiating a test subject with light beams having wavelengths from the visible range to the infrared range, and by detecting, with a single photodetector, the light beams of plural signals having passed through the inside of the test subject. This method is characterized by restraining less a test subject than such cerebral function measuring techniques as MRI and PET.
As for one of clinical applications of this apparatus, it has been reported that the change pattern in hemoglobin in the frontal lobe of a patient of such psychiatric disorders as depression and schizophrenia has a specific characteristic that is not observed in those of healthy normal subjects (Non-Patent Documents 1 and 2). Specifically, there have been found characteristics in which an integral (area) of the temporal wave of hemoglobin of each of test subjects performing a given task is large for healthy normal subjects, small for depression patients, and moderate for schizophrenia patients. In addition, it is observed that the hemoglobin in the schizophrenia patients increases again to form a second peak after task. According to a method disclosed in WO 2005/025421 A1, characteristic parameters are firstly extracted from the wave of a measured hemoglobin change. Then, the Mahalanobis distances between these characteristic parameters and data in a database of disorders are calculated to obtain disorder deciding scores. The scores thus obtained are displayed. In this method, the database of disorders used as the reference for decision are classified and categorized in accordance with the names of disorders given by the user.
[Patent Document 1] WO 2005/025421 A1
[Patent Document 2] WO 2006/132313 A1
[Non-Patent Document 1] Fukuda Masato et al., “Near-infrared spectroscopy as a laboratory test for diagnosis and treatment of psychiatric disorders in clinical practice” Brain Science and Mental Disorders, vol. 14, no. 2 (2003), pp. 155-71.
[Non-Patent Document 2] Fukuda Masato, “Dynamics of Local Cerebral Blood Flow in the Frontal Lobe in Psychoneurotic Disorders—Study Using Optical Topography” Japan Society for the Promotion of Science Grants-in-Aid, Report of Research Results Fiscal Years 2001 to 2002 (Heisei 13 to 14).
The above-described techniques, however, has an aspect of failing to separate the normal controls from the non-normal controls with sufficient accuracy. Moreover, in some cases, categories for separating disorders from each other are not formed based on characteristics of wave in a simple manner.
The present invention focuses on measured area dependency of the temporal wave. Without restricting the measurement area to the frontal lobe, the present invention measures the hemoglobin in plural areas, such as the frontal lobe, the right and left temporal lobes, and the parietal lobe. Then, disorders are classified by using, as characteristic parameters, the slope immediately after task start, the integral (area) during task, the second peak area after task, the center of balance for the entire wave, and the like, which are obtained from the measured temporal waves of hemoglobin. In this way, the normal controls can be separated from the non-normal controls more effectively. In addition, employing stratified classification of disorders enables category formation in a simper manner.
The present invention makes it possible to non-invasively provide information to support diagnosis of disorders.
For an embodiment, disorder decision using an apparatus according to the present invention is performed on a total of 107 test subjects of the following four groups: a normal control group; a schizophrenia patient group; a depression patient group; and a bipolar disorder patient group.
The apparatus for supporting diagnosis of disorders according to the present invention quantifies the above-mentioned characteristics, and automatically classifies the waves on the basis of the quantified characteristics.
Subsequently, the configuration of the apparatus will be described in more detail by referring to
The apparatus for supporting diagnosis of disorders according to the present invention includes: plural light sources 102a to 102d; a modulator; plural means for light emission; and plural means for light reception. The plural light sources 102a to 102d emit light beams having different wavelengths (780-nm wavelength for light sources 102a and 102c and 830-nm wavelength for light sources 102b and 102d). The modulator includes oscillators 101a to 101d (101c and 101d) to respectively modulate the intensities of the light beams emitted from the plural light sources 102a and 102b (102c and 102d), the oscillators 101a to 101d (101c and 101d) having different frequencies from each other. The means for light emission include couplers 104a and 104b each of which couples together the light beams whose intensities have been modulated, via optical fibers 103a and 103b (103c and 103d), respectively, and emits the coupled light beams through optical fibers for light emission 105a (105b). The means for light emission irradiates different positions of the scalp of the object to be tested, that is, of a test subject 106, with the light beams from the couplers 104a and 104b, respectively. The means for light reception respectively include: plural optical fibers for light reception 107a to 107d; and photoreceivers 108a to 108f provided respectively in the optical fibers for light reception 107a to 107d. An end of each of the optical fibers for light reception 107a to 107d is located in the vicinity of each of the positions irradiated by the plural means for light emission. The distance between each light irradiation position and the end of each of the optical fibers for light reception 107a to 107d is kept constant (e.g., 30 mm in this case). The six optical fibers for light reception 107a to 107f collect the light that has passed through the living organism, and the light having passed through the living organism and then collected by the optical fibers for light reception 107a to 107f are subjected to photoelectric conversion respectively by the photoreceivers 108a to 108f. The means for light reception detect the light reflected inside of the test subject, and convert the detected light to electric signals. Photoelectric conversion elements are used as the photoreceivers 108. Photomultiplier tubes and photodiodes are some examples of such photoelectric conversion elements.
The electric signals that represent the intensities of the light having passed through the living organism and are subjected to the photoelectric conversion by the photoreceivers 108a to 108f (hereinafter, the electric signal will be referred to as “living-organism-passed-light intensity signal”) are inputted into lock-in amplifiers 109a to 109h. Note that the photoreceivers 108c and 108d detect the intensities of the light having passed through the living organism and been collected respectively by the optical fibers for light reception 107c and 107d, each which is positioned equidistantly from both of the optical fibers for light emission 105a and 105b. Accordingly, the signal detected by the photoreceiver 108c (108d) is divided into two different lines, and the signals of the two lines are inputted respectively into the lock-in amplifiers 109c and 109e (109d and 1090. The intensity modulating frequencies of the oscillators 101a and 101b are inputted as the reference frequencies into the lock-in amplifiers 109a to 109d whereas the intensity modulating frequencies of the oscillators 101c and 101d are inputted as the reference frequencies into the lock-in amplifiers 109e to 109h. Consequently, the lock-in amplifiers 109a to 109d output, separately, the living-organism-passed-light intensity signals corresponding to the light sources 102a and 102b whereas the lock-in amplifiers 109e to 109h outputs, separately, the living-organism-passed-light intensity signals corresponding to the light sources 102c and 102d.
The passed-light intensity signals of various wavelengths separately outputted by the lock-in amplifiers 109e to 109h are subjected to analog-to-digital conversion by an analog-to-digital converter (AJD converter) 110. Then, the resultant signals are sent to a calculator for controlling measurement 111. The calculator for controlling measurement 111 uses the passed-light intensity signals to calculate, from the detection signals at the detection points, the relative changing amount of the oxyhemoglobin concentration, that of the deoxyhemoglobin concentration, and that of the total hemoglobin concentration. The calculation is performed in accordance with relies on the method described in Non-Patent Document 1. The relative changing amounts thus obtained are stored, in a storage, as time-series data for the plural measurement points. Although
The foregoing description is based on an embodiment where plural kinds of light are separated by a modulation method, but this is not the only possible form. For example, a time-division method may be employed, instead. Specifically, plural kinds of light are discriminated from one another by emitting the plural light at different timings.
A part for input 30, the part for calculating characteristics 20, the part for recording 50, the part for decision 40 are all located in a calculator 112. The part for input 30 is used to input information that is necessary to decide the disorder. The information is inputted using an input screen as shown in
The part for calculating characteristics analyzes the characteristic parameters on the basis of the wave data of the measured local changing amount of oxyhemoglobin, that of deoxyhemoglobin, and the measured total changing amount of hemoglobin. The wave data and the characteristic parameters, together with the information on the measured areas, are sent to the part for recording located in the calculator 112. The part for recording temporarily stocks the measurement information on the test subjects so as to make the execution of the subsequent processing possible. In addition, if there is a definitive diagnosis for a test subject, the part for recording may also function as a database to store the measurement information. The information stocked in the database may be used for automatically adjusting the parameters, which will be described later. In addition, the information stocked in the database may also be used for diagnosing a patient by use of this apparatus. The part for decision located in the calculator 112 makes the decision of disorders by a method that will be described later. The display 60 displays the result of the decision.
Note that the calculator 111 and the calculator 112 are depicted as different calculators in
Although not yet become academically-established, there is a reported fact that language dysfunction (locally existing in the left temporal lobe in most cases) and a functional decline of the frontal lobe are observed in schizophrenia patients and that a functional decline of the frontal lobe and the like are observed in depression patients. It is possible that different disorders cause the functional declines and/or the dysfunction of different areas and of different degrees to take place. This is why the present invention employs the classification based on the data measured in plural areas. The test subjects herein are first classified into two groups: a Type 1 group and a non-Type 1 group. Then, those in the non-Type 1 group are classified into three groups: a Type 2/Type 3 group; a Type 4 group; and a Type 5 group. Finally, those in the Type 2/Type 3 group are classified into two groups: a Type 2 group and a Type 3 group. Note that, as will be shown below, the Type 1 group includes mainly the normal control subjects (hereinafter, sometimes abbreviated as “NC”). Each of the Type 2 group and the Type 5 group includes mainly the schizophrenia patients (hereinafter, sometimes abbreviated as “SC”). The Type 3 group includes the bipolar disorder patients (hereinafter, sometimes abbreviated as “BP”). The Type 4 group includes mainly the depression patients (hereinafter, sometimes abbreviated as “DP”). The use of the data for the appropriate measured areas for each stage characterizes the present invention.
X
—1=C1*integral (area)+C2*slope+C3*second peak area+C4*center of balance (1)
Using the data measured at the frontal lobe and assuming that C1=0.33, C2=0.13, C3=−0.62, C4=−0.70, and thr_1=0.482, it was decided that 36 of all the 107 cases belonged to the Type 1 group. While 67% of the normal control subjects were decided to belong to the Type 1 group, only 6% of the non-normal control subjects were decided to belong to the Type 1 group. When C4 was fixed at zero, the assumption that C1=0.56, C2=0.42, C3=−0.71, and thr_1=0.191 resulted in the highest coincidence ratio with the diagnosis labels. In this case, it was decided that 46% of the normal control subjects and 31% of the non-normal control subjects belonged to the Type 1 group. When, in addition, C3 was fixed at zero, it was decided that 21% of the normal control subjects and the 48% of the normal control subjects belonged to the Type 1 group. When the data measured in the right and left temporal lobes, it was decided that no more than 32 of all the 107 cases belonged to the Type 1 group irrespective of the values of C1, C2, C3, C4, and thr_1. It was decided that only 49% of the normal control subjects, at most, belonged to the Type 1 group. In this case, it was decided that 19% of the non-normal control subjects belonged to the Type 1 group. These facts reveal that the use of the data measured in the frontal lobe is important for separating the Type 1 group from the non-Type 1 group and that the center of balance and the second peak area are the important characteristic parameters.
X
—23=D1*integral (area)+D2*slope+D3*second peak area+D4*center of balance (2)
Using the data measured at the frontal lobe and assuming that D1=0.15, D2=0.15, D3=0.98, D4=0.0, thr_1=0.129, it was decided that 18 of all the 38 cases belonged to the Type 2 group. When each Type group was identified with the label of its main component disorder, the final coincidence ratios of the subjects of each disorder with the diagnosis label were: 67% for NC; 70% for C; 68% for DP; and 66% for BP. When D3 was fixed at zero, the assumption that D1=0.55, D2=0.76, D3=0.0, D4=0.34, and thr_1=0.349 resulted in the highest average coincidence ratio with the diagnosis labels, but the highest average coincidence ratio was no higher than 39%. In addition, the second peak area is the important characteristic parameter for separating the Type 2 group from the Type 3 group.
As has been described thus far, in this embodiment, the highest coincidence ratio with the diagnosis label was obtained when the data on the frontal lobe, the data on the left temporal lobe and the data on the frontal lobe were used at the first, second, and third stages, respectively. When other combinations of measured areas were used, the best coincidence ratio resulted from a case where: the data on the frontal lobe, the data on the left temporal lobe, and the data on the right temporal lobe were used at the first, second, and third stages, respectively. Nonetheless, in this case, the coincidence ratios with the diagnosis labels were: 67% for NC; 65% for SC; 55% for DP; and 67% for BP. The average coincidence ratio of this case was not as high as the average coincidence ratio of the case where: the data on the frontal lobe, the data on the left temporal lobe, and the data on the frontal lobe were used at the first, second, and third stages, respectively.
The apparatus of the present invention has a function of accumulating data in the database. The data in the database may change, and thus the apparatus has a system for automatically adjusting the classification model along with the change. Description of this system will be given next. Note that automatic adjustment refers to a function of optimizing the parameters used in each model with respect to the data in the database.
Firstly, the optimization of the model described in
Subsequently, the optimization of the model described in
pNC(j,n)+pS(j,n)+pD(j,n)+pBP(j,n)=1
The optimization is executed by selecting the thresholds that make the existing probabilities of the disorders as disproportionate as possible in each of the Type groups. The entropy sum E(j) corresponding to the combination j of thresholds (thr_a, thr_b) can be expressed by the following equations.
In the above equations, pn represents the proportion of the data included in the Type n when the combination j of thresholds is employed. Here, the combination of the thresholds that results in the minimum entropy sum E(j) is assumed to give the best classification (i.e., the best clustering). Minimizing the entropy corresponds to the threshold selection that makes the existing probabilities of the disorders as disproportionate as possible in each of the Type groups.
Lastly, the optimization of the model described in
Subsequently, another embodiment that is different from the above-described embodiment will be described. In the apparatus configuration shown in
The classification of this embodiment was executed by using a data combination that is changed depending on the disorder. This is because the inventors considered the fact that, in the classification used in the previous embodiment, the measured data combinations that resulted in the highest coincidence ratios of the disorders with the diagnosis labels differed from one diagnosis to another. A classification was executed on a total of 121 test subjects (specifically, 55 NC subjects, 30 SC patients, 26 DP patients, and 10 BP patients) in the order of BP→SC→DP and NC. Which piece of data had to be used at each stage was determined on the basis of the coincidence ratios of various data combinations with diagnosis labels shown in Table 1. FRONT, LEFT, and RIGHT in Table 1 refer respectively to the frontal lobe, the left temporal lobe, and the right temporal lobe. In addition, the highest coincidence ratio for each group is shown in boldface. For BP, the data on the right temporal lobe were used at the first stage (a classification model shown in
Lastly, an example of simple classifications of disorder will be described below. In clinical practice, there is a simple case where two different disorders have to be distinguished from each other. For example, there is a case where depression and bipolar disorder have to be distinguished from each other. By using the normalized parameters (integral (area), slope, and center of balance), the following calculation is performed:
Z=2*integral (area)+5*slope−2*center of balance
In this event, the values obtained by calculating by use of the data measured in the frontal lobe, the data measured in the left temporal lobe, the data measured in the right temporal lobe are expressed respectively by Z_front, Z_left, and Z_right. For depression patients, a relationship (Z_front+Z_left)/2<Z_right tends to hold true. For bipolar disorder patients, a relationship (Z_front+Z_left)/2>Z_right tends to hold true. By use of these relationships, 20 depression patients and 15 bipolar disorder patients were classified. Fifteen of the 20 depression patients were decided correctly whereas ten of the 15 bipolar disorder patients were decided correctly.
As has been described thus far, the use of the data measured in plural areas allows an effective classification of disorders to be executed.
The present invention can be used for an apparatus for supporting and checking diagnosis of disorders such as psychiatric disorders.
Number | Date | Country | Kind |
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2007-133766 | May 2007 | JP | national |
Filing Document | Filing Date | Country | Kind | 371c Date |
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PCT/JP2008/051628 | 2/1/2008 | WO | 00 | 5/13/2010 |