USOO8406838B2

(12) United States Patent (10) Patent No.: US 8.406,838 B2

Kato (45) Date of Patent: Mar. 26, 2013
(54) APPARATUS FOR EVALUATING 6,587,703 B2 7/2003 Cheng et al.
BIOLOGICAL FUNCTION, A METHOD FOR 6,640,130 B1 10/2003 Freeman et al.
6,723,047 B1 4/2004 Yamamoto et al.
EVALUATING BIOLOGICAL FUNCTION, A 6,901,284 B1 5/2005 Maki et al.
LIVING BODY PROBE, A LIVING BODY 7,065,392 B2 6/2006 Kato
PROBE MOUNTING DEVICE, A LIVING 7,187,962 B2 3/2007 Shingo
BODY PROBE SUPPORT DEVICE AND A 2004.0054271 A1* 3, 2004 Maki et al. .. ... 600,341
LIVING BODY PROBE MOUNTING 2004/0242979 A1* 12/2004 Kawasaki ..................... 600,323
ACCESSORY FOREIGN PATENT DOCUMENTS
JP O9-135825 5, 1997
(76) Inventor: Toshinori Kato, Tokyo (JP) JP 09-149903 6, 1997
JP O9-238914 9, 1997
(*) Notice: Subject to any disclaimer, the term of this JP 2000-237194 9, 2000
patent is extended or adjusted under 35 JP 2002-177281 6, 2002
U.S.C. 154(b) by 1656 days. JP 2003-10188 1, 2003
JP 2003-75331 3, 2003
JP 2003-144437 5, 2003
(21) Appl. No.: 11/655,998 WO WOOOf 74572 12/2000
WO WOO3,068070 8, 2003
(22) Filed: Jan. 22, 2007
* cited by examiner
(65) Prior Publication Data
Primary Examiner — Eric Winakur
US 2008/O262327 A1 Oct. 23, 2008 Assistant Examiner — Chu Chaun (JJ) Liu
(74) Attorney, Agent, or Firm — Jacobson Holman PLLC
Related U.S. Application Data
(63) Continuation of application No. PCT/JP2005/013327, (57) ABSTRACT
filed on Jul. 20, 2005. The apparatus for evaluating biological function of the
present invention has living body probes 1, a behavioral infor
(30) Foreign Application Priority Data mation measuring part 2 and an apparatus body 3, and it
utilizes near-infrared spectroscopy to evaluate biological
Jul. 20, 2004 (JP) ................................. 2004-211012 function; apparatus body 3 has a controller 8 for calculating
(based on light information from living body probes 1) a
(51) Int. Cl. variety of parameters derived from two-dimensional dia
A6B 5/1455 (2006.01) grams showing relationships between changes in oxyhemo
(52) U.S. Cl. ........ 600/322; 600/310; 600/323; 600/324; globin and changes in deoxyhemoglobin and two-dimen
6OO/328 sional diagrams showing relationships between absolute
(58) Field of Classification Search .................. 600/310, amounts of oxyhemoglobin and absolute amounts of deoxy
600/322,323,326, 328, 340, 344, 476, 32: hemoglobin, a behavioral information input part for entering
356/39, 40 behavioral information measured by means of behavioral
See application file for complete search history. information measuring part 12, and a display part 10 for
performing various types of image displays based on various
(56) References Cited parameters calculated by means of controller 8 and/or behav
ioral information entered in the behavioral information input
U.S. PATENT DOCUMENTS part.
5,803,909 A 9, 1998 Maki et al.
5,853,370 A * 12/1998 Chance et al. ................ 600,323 29 Claims, 92 Drawing Sheets

Ho Y-axis)
Ab (y-axis)
Atibtyraxis

to saxis

2- point
ox-axis

Sco X-axis)
U.S. Patent Mar. 26, 2013 Sheet 1 of 92 US 8.406,838 B2

Figure 1.

(A)

0.4 stimulus application period

--> -- oxy-Hb 7
0.3 -- deoxy-Hb 2
0.2

(B)
stimulus application period
---0-- Oxy-Hb
-- deoxy-Hb

Measurement time (Sec)

U.S. Patent Mar. 26, 2013 Sheet 2 of 92 US 8.406,838 B2

Figure 2
Behavioral
information
measuring part

Sampling speed Behavioral

information
living body probe -i.ghts intensity
adjustor adjuster input part

Light-emitting
element

Light-receiving
element
U.S. Patent Mar. 26, 2013 Sheet 3 of 92 US 8.406,838 B2

Figure 3
U.S. Patent Mar. 26, 2013 Sheet 4 of 92 US 8.406,838 B2

Figure 4

(B)
U.S. Patent Mar. 26, 2013 Sheet 5 Of 92 US 8.406,838 B2

Figure 5

(B)
U.S. Patent Mar. 26, 2013 Sheet 6 of 92 US 8.406,838 B2

Figure 6

Gyrus-probe angle

5' 8O

NS 1
SO
O'

IS's
90'
X* 90'
15
Direction of gyrus
U.S. Patent Mar. 26, 2013 Sheet 7 Of 92 US 8.406,838 B2

Figure 7

nOe.ITeul3D. (G)

xeºrteauneo (O)

Iear?ezuyeno (g)

rITe?îuneo
U.S. Patent Mar. 26, 2013 Sheet 8 of 92 US 8.406,838 B2

Figure 8

b O) (A)

"A

b 5 (C)

b Di (D)
U.S. Patent Mar. 26, 2013 Sheet 9 Of 92 US 8.406,838 B2

Figure 9

la lb la b

(A) (B)

,sae<
U.S. Patent Mar. 26, 2013 Sheet 10 of 92 US 8.406,838 B2

Figure 10

Hb (Y-axis)

Athlb (y' -axis)

N
thb (Y-axis)

Measurement point C

HbOz (X-axis)

SCO2 (X-axis)
U.S. Patent Mar. 26, 2013 Sheet 11 of 92 US 8.406,838 B2

8.
U.S. Patent Mar. 26, 2013 Sheet 12 of 92 US 8.406,838 B2

Figure 12

C)

.
G
O
C
?
C
O
X
CD
C
D
ton
>
X
O

Capillary Vein

Figure 13

E
C

Event - 4
U.S. Patent Mar. 26, 2013 Sheet 13 of 92 US 8.406,838 B2

Figure 14

(A) É
<

A HbO)

(B)
c
SE
K

A HbO)
U.S. Patent US 8.406,838 B2

Figure 15
U.S. Patent Mar. 26, 2013 Sheet 15 Of 92 US 8.406,838 B2

Figure 16

Maximum Watering-the-garden effect

Total Hb/ScC2 increase
mMmm
TotalHb

Total Hb/ScOz decrease S.

Maximum FORCE effect
(A)

Deoxyhb)
(thb) =OxyHb-i-DeoxyHb

(ScC2) = (OxyHb-DeoxyHb)

Oxyhb

(B)
U.S. Patent Mar. 26, 2013 Sheet 16 of 92 US 8.406,838 B2

*
U.S. Patent Mar. 26, 2013 Sheet 17 Of 92 US 8.406,838 B2

Figure 18

(A)
vector components causing
Hb-axis (concentration: mol/l) variation in the moment of inertia
AP (A Pt Hb, A Fth, AT t Hb)
Measurement point q: AP, AF, AT
tho-axis Measure
point p
Components of oxygen exchange
rotational motion
( A LSc0, A Nsco, AKsco,)
HbO2-axis (Concentration: mol/l)
6 Angle
ScO-axis

(B)
Vector components causing
Hb-axis (concentration: mol/l) variation in the moment of inertia
Pd (Pt Hb -- A PtHb, Ft. Kb AFt Hb, Tt Hb -- A T thL )
Measurement
point 9 P, F, T
Po
K-angle
components of oxygen exchange rotational motion
(ALsco, - LSc0, Nsco, ANsco, Ksc 0, - A KSco.)
HbO2-axis (concentration: mol/l)

ScOz-axis
U.S. Patent Mar. 26, 2013 Sheet 18 of 92 US 8.406,838 B2

Figure 19

Hb-axis (concentration: mol/light functional pixel.)

thb-axis

Movement of center of gravity coordinates G

r

HbO-axis (concentration: mol/light functional pixel)

ScO2-axis
U.S. Patent Mar. 26, 2013 Sheet 19 of 92 US 8.406,838 B2

Figure 20

Ho-axis
(concentration:
mol/light functional pixel)
thb-axis

Movement of center of rotation C

ibO-axis
(concentration: mol/light functional pixel)

ScC2-axis
U.S. Patent Mar. 26, 2013 Sheet 20 Of 92 US 8.406,838 B2
U.S. Patent US 8.406,838 B2

Figure 22

(g)v
U.S. Patent US 8.406,838 B2

Figure 23
U.S. Patent Mar. 26, 2013 Sheet 23 of 92 US 8.406,838 B2

Figure 24

*
·
·
*
·
...
«
?i
,
•
4.
…
„

3A-T(3)nTe
U.S. Patent Mar. 26, 2013 Sheet 24 of 92 US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 25 Of 92 US 8.406,838 B2

Figure 26
U.S. Patent Mar. 26, 2013 Sheet 26 of 92 US 8.406,838 B2

Figure 27
U.S. Patent Mar. 26, 2013 Sheet 27 Of 92 US 8.406,838 B2

Figure 28

Hb Differentials of thb (rate of change in thb)

t

Time Title

(A) (B)

(C)
U.S. Patent US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 29 Of 92 US 8.406,838 B2

Figure 30

aq?seaogf33pu.e?0gA8o0ue3s
U.S. Patent Mar. 26, 2013 Sheet 31 of 92 US 8.406,838 B2

Figure 32

Start

Measurement mounting
device mounted

iiving body probes set up S2

S3
Light irradiated from
light-emitting elements

Licht received by SA
light-receiving elements

Data analysis of 5
light functional pixel
data within channels

S6
Selection within
channels Are given
criteria satisfied?

Data analysis of
light functional pixel
data between channels

Selection along
channels. Are given
criteria satisfied ? N
y
Baseline data measured S9
with living body at rest
Data analysis and data
display.

S10
Data measured when a task
Data analysis and data
display is presented to
the living body.
U.S. Patent Mar. 26, 2013 Sheet 32 Of 92 US 8.406,838 B2

Figure 33

Site 1

Response time RT
(A)

Site 2

Site 1
(B)
U.S. Patent Mar. 26, 2013 Sheet 33 Of 92 US 8.406,838 B2

Figure 34

(A)

(B)

(C)
U.S. Patent Mar. 26, 2013 Sheet 34 of 92 US 8.406,838 B2

Figure 35

Integral values

(A)

Time (S)

Integral values

(B)

Time (S)

Integral values

(C)

Time (s)
U.S. Patent Mar. 26, 2013 Sheet 35 of 92 US 8.406,838 B2

{3.3
U.S. Patent Mar. 26, 2013 Sheet 36 of 92 US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 37 Of 92 US 8.406,838 B2

Figure 38

Measurement starting point

Minimum Absolute value

response time of inde
Behavior time (RT)
Origin. O
Time (t)

Figure 39

Ya

Measurement point K
U.S. Patent Mar. 26, 2013 Sheet 38 of 92 US 8.406,838 B2

Figure 40

Left/right:
Maximum both-sides correlation coefficient; n x in
X/ (in x n)) x 100

Display of r <0. 6

Display of r <0.99

Right network share (percent use)

Left 100% x7 in x (n-1))} x 100

Right maximum;
in x (n-1) : same-side correlation coefficient
U.S. Patent Mar. 26, 2013 Sheet 39 Of 92 US 8.406,838 B2

3.
U.S. Patent Mar. 26, 2013 Sheet 40 of 92 US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 41 of 92 US 8.406,838 B2

Figure 43

's taskA
3.

Seconds

-10 Seconds

-30 Deoxyhemoglobin task ratio = Task A / Task B (channel 9)

U.S. Patent Mar. 26, 2013 Sheet 42 of 92 US 8.406,838 B2

Figure 44

(€)
U.S. Patent Mar. 26, 2013 Sheet 43 of 92 US 8.406,838 B2

Figure 45

(E)
U.S. Patent Mar. 26, 2013 Sheet 44 of 92 US 8.406,838 B2

Figure 46
U.S. Patent Mar. 26, 2013 Sheet 45 of 92 US 8.406,838 B2

Figure 47 4 4

b
a

Centerline (venous Sinus)

(A)
U.S. Patent Mar. 26, 2013 Sheet 46 of 92 US 8.406,838 B2

Figure 48

?eueoreeTeano

aearTeguneo

Iºe?qoarTe
U.S. Patent Mar. 26, 2013 Sheet 47 of 92 US 8.406,838 B2

Figure 49

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es

we

See Steel
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U
g e-S a1

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G
ser

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D O
E. p

:s
Ns s.a D
c
4.
D
R
O) c

an

2 ? Ne

"cs
O

r
U.S. Patent Mar. 26, 2013 Sheet 48 of 92 US 8.406,838 B2

Figure 50
U.S. Patent Mar. 26, 2013 Sheet 49 Of 92 US 8.406,838 B2

Figure 51

Torus occipitalis

(A)

Point of intersection p of the line joining the left and

right outer ear canals and the line joining the glabella
and the torus occipitalis

Outer ear Canal

(B)
U.S. Patent Mar. 26, 2013 Sheet 50 Of 92 US 8.406,838 B2

is
U.S. Patent Mar. 26, 2013 Sheet 51. Of 92 US 8.406,838 B2

Figure 53

)
E
(
U.S. Patent Mar. 26, 2013 Sheet 52 Of 92 US 8.406,838 B2

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pºuerltansoqu
quzaeirfôsG iquer69s*

zque r6.3s Tnuautôes

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O
(
U.S. Patent Mar. 26, 2013 Sheet 53 of 92 US 8.406,838 B2

(V)
U.S. Patent Mar. 26, 2013 Sheet 54 Of 92 US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 55 Of 92 US 8.406,838 B2

Figure 57

i
s
U.S. Patent US 8.406,838 B2

Figure 58

Tte?a2s6eum
U.S. Patent Mar. 26, 2013 Sheet 57 Of 92 US 8.406,838 B2

Figure 59

L'O ZTO
Change in absorption coefficient at 780 nm.
U.S. Patent US 8.406,838 B2
Figure 60

uu 08L a e queForggeoo uokadrosae up ebueuo

U.S. Patent Mar. 26, 2013 Sheet 59 of 92 US 8.406,838 B2

Figure 61
U.S. Patent Mar. 26, 2013 Sheet 60 of 92 US 8.406,838 B2

Figure 62

( N
C O O

3. G G
U.S. Patent Mar. 26, 2013 Sheet 61 of 92 US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 62 of 92 US 8.406,838 B2

Figure 64

nbquºe?anosdW
U.S. Patent Mar. 26, 2013 Sheet 63 of 92 US 8.406,838 B2

Figure 65

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U.S. Patent Mar. 26, 2013 Sheet 64 of 92 US 8.406,838 B2

Figure 66

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G
(

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v
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§§
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U.S. Patent Mar. 26, 2013 Sheet 65 of 92 US 8.406,838 B2

Figure 67
U.S. Patent Mar. 26, 2013 Sheet 66 of 92 US 8.406,838 B2

Figure 68

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//

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s6puo as
U.S. Patent Mar. 26, 2013 Sheet 72 Of 92 US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 73 Of 92 US 8.406,838 B2

Figure 75

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2:0-
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Figure 77

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U.S. Patent Mar. 26, 2013 Sheet 76 of 92 US 8.406,838 B2

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14:0-

(OI/I)puo .es
U.S. Patent Mar. 26, 2013 Sheet 78 of 92 US 8.406,838 B2

Figure 80

$40 700
U.S. Patent Mar. 26, 2013 Sheet 79 of 92 US 8.406,838 B2

Figure 81

Parameter

Behavioral information
U.S. Patent Mar. 26, 2013 Sheet 80 Of 92 US 8.406,838 B2

Figure 82

Individual data
from desired sites

1 2 3 4 5 6 Problems answered correctly

(A)

Individual data
from desired sites

7 8 9 10 Problems answered incorrectly

(B)
U.S. Patent Mar. 26, 2013 Sheet 81. Of 92 US 8.406,838 B2

Figure 83

Correct
Summed data
A
for all examinees COect

Degree of
individual effect

a b c d Examinee

(B)
U.S. Patent US 8.406,838 B2

Figure 84
U.S. Patent Mar. 26, 2013 Sheet 83 of 92 US 8.406,838 B2

Figure 85

Time axis AHb axis

AHbO2 axis

Time axis AHb axis

(B)
U.S. Patent Mar. 26, 2013 Sheet 84 of 92 US 8.406,838 B2

aic: ; of ex}xy terrogio:

------....*...*&-s:

& 3:3: Kigiri is air;

U.S. Patent Mar. 26, 2013 Sheet 85 of 92 US 8.406,838 B2

Figure 87

/
23

(A)

23

(B)
U.S. Patent Mar. 26, 2013 Sheet 86 of 92 US 8.406,838 B2

Figure 88

Inferior temporal gyrus

2) y
24

Figure 89
U.S. Patent Mar. 26, 2013 Sheet 87 Of 92 US 8.406,838 B2

Figures 90

(A)
Outer ear canal
Outer eyelid

Broca's area Motor area

(B)
Wernicke's area
Brodman 10
(BA10)

Glabella

Outer ear canal

Outer eyelid

27 27a

(C) 14
U.S. Patent Mar. 26, 2013 Sheet 88 of 92 US 8.406,838 B2

Figure 91
U.S. Patent Mar. 26, 2013 Sheet 89 of 92 US 8.406,838 B2

Figure 92

(A) - 30
U.S. Patent Mar. 26, 2013 Sheet 90 of 92 US 8.406,838 B2

' &
''
U.S. Patent Mar. 26, 2013 Sheet 91. Of 92 US 8.406,838 B2
U.S. Patent Mar. 26, 2013 Sheet 92 Of 92 US 8.406,838 B2

Figure 95

ON

Right brain wn
O
We

CN

Right brain
O

Right brain ra

Right brain
3.
 US 8,406,838 B2
1. 2
APPARATUS FOREVALUATING However, even if accurate location information could have
BIOLOGICAL FUNCTION, A METHOD FOR been measured by the technique of optical CT, by the time
EVALUATING BIOLOGICAL FUNCTION, A light had passed through the skull to the brain Surface and into
LIVING BODY PROBE, A LIVING BODY the brain, it was absorbed, and so the method was of no
PROBE MOUNTING DEVICE, A LIVING 5 practical use.
BODY PROBE SUPPORT DEVICE ANDA Accordingly, in 1991, the present inventor Kato devised
LIVING BODY PROBE MOUNTING and corroborated a new basic principle of NIRS imaging
ACCESSORY (near-infrared spectroscopy functional imaging) for deter
10
mining location information by means of the location of a
This is a continuation of PCT/JP05/013327 filed Jul. 20, probe on the brain Surface and the response to a measurement
2005 and published in Japanese. target.
An apparatus for evaluating biological function, a method In addition, the present inventor and his colleagues con
for evaluating biological function, a living body probe, a ducted light stimulus experiments in humans in which the
living body probe mounting device, a living body probe Sup brain was partially irradiated with near-infrared light, which
port device and a living body probe mounting accessory 15
showed, as a result, that localized brain function distribution
TECHNICAL FIELD can be monitored at the bedside, and proved that it is possible
to create images of localized brain function using this method
The present invention concerns an apparatus for evaluating and a bedside noninvasive method for detecting local brain
biological function for the purpose of measuring and evalu function (Sachio Takashima, Toshinori Kato, et al., “NIR
ating biological function based on transmitted, reflected, scat Spectroscopy niyoru kyokusho nouketSuryu hendou no kan
tered or diffused light that is detected from a living body after satsu'. Shinshingaiji (sha) no iryou ryouiku ni kansuru
its interaction with the living body by means of a living body sougouteki kenkyu no houkokusho "Observation of varia
probe, a method for evaluating biological function, a living tion in local brain blood flow by means of near-infrared spec
body probe, a living body probe mounting device, a living 25 troscopy, in Comprehensive Research Report Concerning
body probe Support device and a living body probe accessory; Medical Care for Children (People) with Disabilities (Japan
and in particular it concerns an apparatus for evaluating bio Ministry of Health and Welfare), p. 179-181 (1992); Kato T.
logical function and a method for evaluating biological func Kamei A. et al., “Human visual cortical function during
tion that utilize near-infrared spectroscopy (NIRs), and a photic stimulation monitoring by means of near-infrared
living body probe, a device for mounting a living body probe, 30 spectroscopy”, J Cereb Blood Flow Metab. 13:516-520
a living body probe Support device and a living body probe (1993).
mounting accessory. This basic principle of near-infrared spectroscopy brain
functional imaging (NIRS imaging) is currently utilized in,
BACKGROUND OF THE INVENTION for example, techniques for graphically displaying the func
35 tional topography (hemoglobin distribution, i.e., the display
In recent years, a method was proposed in 1977 by F. F. of variation in blood volume, reflecting brain activity, like a
Jobsis in which weak near-infrared rays (680-1300 nanom topographical map) of the brain Surface in the frontal region,
eters) are irradiated from on the skin of the head through the the occipital region and the like, and in pioneering techniques
skull and into the brain to measure changes in concentration for obtaining information on brain activity. Subsequent tech
of oxygenated hemoglobin (Oxy-Hb, HbO) and changes in 40 niques proposed for the graphical display of brain function
concentration of deoxygenated hemoglobin (Deoxy-Hb, Hb) include, for example, the inventions described in Japan unex
in the blood at the brain surface (cerebral cortex) just inside amined patent publication nos. 2003-144437, 2003-75331,
the skull. 2000-237194, H9-135825, 2002-177281 and 2003-10188.
Since that time, research on the measurement of tissue The inventions proposed in these publications concern
oxygen concentration by means of this near-infrared spec 45 apparatus for measuring the interior of a living body by irra
troscopy (NIRS) method has progressed rapidly. diating the living body with near-infrared light from a plural
In general, the near-infrared spectroscopy method has the ity of irradiation sites and detecting light transmitted through
advantages that metabolism of individual tissue can be mea the living body at a plurality of detection sites; this is called
sured noninvasively from the surface of the body (noninva Optical Topography (registered trademark), and changes in
siveness), it can furthermore be implemented by a simple and 50 concentration of oxygenated hemoglobin and deoxygenated
convenient apparatus (portability), and, in addition, it differs hemoglobin in the blood are calculated for each measuring
from imaging methods such as PET (positron emission CT), point based on light intensity signals measured at a plurality
f-MRI (functional magnetic resonance imaging) in that it of measuring points and displayed topographically.
makes it possible to obtain real-time measurements of It is furthermore utilized in pioneering techniques for
changes in tissue metabolism in the brain, muscles and the 55 obtaining information on brain activity, which occurs as rap
like over time (temporality); it has thus given rise to expec idly as electrical activity.
tations of a wide range of application in uses such as brain For example, Gratton et al., by means of NIRS imaging,
function monitoring, evaluation of muscle rehabilitation in have detected a faint light that varies by means of electrical
physical therapy, and exercise physiology. activity by adding 1-wavelength near-infrared light to a signal
Jobsis previous method was an attempt at noninvasive 60 (occurring) approximately 100 ms before a brain blood flow
brain oxygen monitoring, and an optical tomography method response occurs from a stimulus consistent with an electrical
(optical CT) was devised, in which the brain was cross-sec response (Gratton G, Fantini S, Corballis PM, et al. Fast and
tioned in layers by Straight-line light in an attempt to obtain localized event-related optical signals (EROS) in the human
accurate oxygen information from in the depths of the brain, occipital cortex: comparisons with the visual evoked poten
(Shinohara, Y. et al., Optical CT imaging of hemoglobin 65 tial and fMRI. NeuroImage 6, 168-180, 1997).
oxygen-Saturation using dual-wavelength time gate tech Or, a technique has been proposed as a game or apparatus
nique. Adv Exp Med Biol, 1993.333: p. 43-6). for displaying one’s intent, by utilizing changes in cerebral
 US 8,406,838 B2
3 4
blood flow and outputting them externally (International pub Smoothing were employed, but in the end, it was impossible
lishedpatent application no. WOOO/074572 pamphlet, Yama to measure just one stimulus application, and only addition
moto et al.). average mode measurements or measurements of large, quite
Patent reference 1. Japan unexamined patent publication slow changes, in units of seconds, were possible.
no. 2003-144437 Patent reference 2. Japan unexamined (3) Previous measuring techniques were based on the
patent publication no. 2003-75331 Patent reference 3. Japan widely held physiological concepts that (a) electrical activity
unexamined patent publication no. 2000-237194. Patent ref occurs simultaneously with a stimulus, and then (b) oxygen
erence 4. Japan unexamined patent publication no. metabolism activity and blood flow activity become stronger
H9-135825 Patent reference 5. Japan unexamined patent pub (occurring after a delay of 2-3 seconds and reaching a peak at
lication no. 2002-177281 Patent reference 6. Japan unexam 10 10-15 seconds). Consequently, with a technique for indepen
ined patent publication no. 2003-10188 Patent reference 7. dent measurement of oxyhemoglobin, deoxyhemoglobin,
International published patent application no. WO 00/074572 total hemoglobin, cytochrome, and reaction patterns of opti
pamphlet cal signals approximately 100ms after a stimulus application,
there was no reason for high-speed measurement, and without
DISCLOSURE OF THE INVENTION 15 improvement in the S/N ratio, measurement accuracy would
not be improved. Namely, in the past, there were limitations to
Problems the Invention Attempts to Solve measuring techniques relying on hemodynamic and meta
bolic responses of measurement targets.
Previous measurement techniques have had the following (4) In addition to NIRS (near-infrared spectroscopy),
problems. methods such as EEG (electroencephalograms), MEG (mag
(1) The problems to be resolved by the new basic principle netoencephalograms), MRI (magnetic resonance imaging)
of NIRS imaging (near-infrared spectroscopy functional and PET (positron CT) are also known for measuring brain
imaging), in which location information is determined by function. However, with these previous measurement tech
means of the location of probes on the brain surface and the niques, it was difficult, without addition average, to continu
response of a measurement target, become clear when we 25 ously measure brain responses in milliseconds to the point
compare techniques of determining location information by where network function could be measured.
means of magnetic resonance imaging (MRI) and techniques Because the oxygen partial pressure of the capillaries is
of determining qualitative information. Namely, NIRS imag approximately equal to that of the tissue, it has been recog
ing does not forman image by collecting a square matrix (of nized, since times past, that in measuring tissue oxygen con
voxels), as does MRI. Namely, boundaries with adjacent 30 centration, it is extremely important to collect oxygen con
locations are unclear. centration data from the blood of the capillaries. The near
Because two probes are utilized, for light incidence and infrared spectroscopy method, however, takes measurements
detection, it has been impossible to tell, according to the noninvasively, from the surface of the body, and because
distance between the two probes, whether or not light reached changes in the signal are thus the Sum of responses occurring
to the interior of the brain without seeing a response from the 35 in the regions existing on the light path, its quantifiability, i.e.,
brain. Previously, images were displayed in proportion to the spatial resolution, is considered to be inferior. Data shown in
size (strength) of this brain response, and the bigger the FIG. 1(A) was identified in the past as predominantly capil
response was, the better it was considered. lary data, as is clearly shown in the literature by H. Marc
However, the distance from the surface of the skull to the Watzman et al. (Arterial and venous contributions to near
brain tissues is affected by individual differences, site differ 40 infrared cerebral oximetry”, Anesthesiology 2000; 93:947
ences, differences according to the size of the cerebral blood 53) and FIG. 8 of Japan published patent application
vessels and differences in the shape of the gyri and Sulci, the H9238914, but the present inventor believes that this is inevi
brain and skull are not uniform; and in the past, technical tably predominantly venous data, by reason of the facts that it
attention was not given to this non-uniformity. Namely, the was obtained by measuring a site where a vein typically exists
signal-to-noise ratio (S/N) of the optical signals detected by 45 on the light path, and the apparatus was configured with wide
each pair of probes was different, and the size of the range of spacing (approximately 30 mm) between the measurement
area measured was also different. In the past, those measure points.
ment sites were joined together, like contour lines, and dis This is because the capillaries are structured in Such a way
played graphically. that application of stimulus is likely to result in a divergence
(2) In MRI, the nature of the measurement target is deter 50 between the variation in the amount of redblood cells and that
mined by a matrix (of voxels) of signal strengths. In NIRS of the blood serum component. Namely, in the capillaries, the
imaging, however, analysis and weighting of a response from red blood cells and the serum move at different speeds, and
the living body at a measurement target becomes an important changes in the hematocrit or changes in total hemoglobin are
technique. In the past, this was no more than a technique for therefore more likely to occur there than in the veins; conse
independent measurement of oxyhemoglobin, deoxyhemo 55 quently, mirror-image changes in oxygenated hemoglobin
globin, total hemoglobin, cytochrome, and reaction patterns and deoxygenated hemoglobin are less likely to occur there
of optical signals approximately 100 ms after a stimulus than in the veins. Predominantly capillary data is therefore
application. A simple signal strength of this kind is directly considered necessarily to be that of FIG. 1 (B), which shows
affected by the S/N ratio, and its measurement sensitivity an asymmetrical mode of change, because of conclusions
does not improve. In particular, fluctuation of channels with a 60 obtained from the research of the present inventor. If this is the
bad S/N ratio shows greaterchanges in signal strength than do case, then previous measuring apparatus can be said to be
channels with a good S/N ratio, and image displays were thus configured based on an erroneous theoretical perception.
dependent on high noise channels and differed from reality. In addition, even in the rare case when a previous measur
In addition, venous signals were likely to be mixed with ing apparatus identifies the data shown in FIG. 1 (B) as true
capillary signals, causing the precision of results to deterio 65 predominantly capillary data, it is impossible to tell whether
rate markedly. In order to improve the S/N ratio, measures data being collected is predominantly capillary data or pre
Such as addition average and using low-pass filters for dominantly venous data by comparing this data with the
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5 6
predominantly venous data of FIG. 1(A) during the period up Secondly, it takes as its object the provision of an apparatus
until changes occur in the tissue by using a conventional for evaluating biological function, a method for evaluating
measuring apparatus, which is confined to the output of FIGS. biological function, and a living body probe that distinguishes
1(A) and (B), because before the application of stimulus as much as possible between information from the capillaries,
(including both internal stimuli from physiological effects which reflects tissue metabolism, and information from out
and external stimuli), that is, at rest, before changes occur in side the tissue (for example, the arteries and veins), and, in
the tissue (in the figures, baseline the period up to approxi order to exclude information corresponding to noise, detects
mately 8 seconds), the characteristics of change over time for differences in the S/N ratio to identify image distortion, thus
both predominantly capillary data and predominantly venous providing high speed and accuracy to make it possible to
data are largely convergent. If we take into account this time 10 compensate for the low spatial resolution of previous near
lag together with the extremely low probability of collecting infrared spectroscopy methods; this makes it possible to dis
predominantly capillary data because of the wide settings of tinguish capillary responses, metabolic responses and the
the measurement point intervals (approximately 30 mm), we like, while at the same time making it possible to identify
cannot expect a Sufficient contribution to on-site medicine. oxygen metabolism activity in the capillaries corresponding
In addition, because previous measuring apparatus utiliz 15 to behavioral information.
ing near-infrared spectroscopy only measure absolute values Third, it takes as its object the provision of an apparatus for
and changes in oxygenated hemoglobin and deoxygenated evaluating biological function, a method for evaluating bio
hemoglobin concentration (and even this data is highly inac logical function, and a living body probe that do not simply
curate), and because theories of brain physiology, Such as the monitor changes in oxygen concentration and display them
correlation between these measured data and vasodilatation/ graphically, but that make it possible to separate out in detail
vasoconstriction arising in the cerebral blood vessels, and the the Volume of the measurement target, namely, the Voxel
involvement of the oxygen consumption rate and changes in components, and make it possible, by lessening differences in
the hematocrit in the capillaries accompanying changes in S/N ratio between the Voxels, correcting them, or measuring
total hemoglobin, have not been adequately understood, these new indexes derived from measured parameters that are not
apparatus have therefore remained in the realm of monitors 25 easily affected by S/N ratios, to easily and conveniently dis
for showing changes in concentration of hemoglobin and the tinguish functional data, including location and time infor
like, or simple Scientific experimental tools. In addition, even mation.
in two-dimensional image displays, when a plurality of sites Fourth, it takes as its object the provision of a living body
are measured, the S/N ratio will differ between the sites, so probe mounting device, a living body probe Support device,
that channels with low S/N ratios are emphasized, and so on, 30 and a living body probe mounting accessory for use with the
resulting in a distorted image, and so they were not meaning above-mentioned living body probe.
ful apparatus capable of evaluating function by means of
image displays. Means for Solution of the Problems
(5) Neuron activity brings a need for oxygen consumption
and oxygen Supply. In this case, oxygen is thought to be 35 The apparatus for evaluating biological function is an
supplied through the glial cells from 7-micron red blood cells apparatus for evaluating biological function having a plural
in the 5-micron capillaries. The oxygen concentration ity of living body probes provided with light-emitting ele
decreases in the capillaries that Supplied the oxygen, and then ments for irradiating light to specified sites of a living body
oxyhemoglobin is supplied from the arterial side. Because it and light-receiving elements for receiving and detecting light
was not previously possible to measure this brain microcir 40 exiting the living body, a behavioral information measuring
culation, tissue oxygen partial pressure was measured inva part for measuring behavioral information of the aforemen
sively by inserting a needle into the intercellular spaces of the tioned living body, and an apparatus body for entering light
neurons. In actuality, since Roy and Sherrington (Roy C S. information detected by the aforementioned living body
Sherrington CS: On the regulation of the blood-supply of the probe and behavioral information measured by the aforemen
brain. J. Physiol 11, 85-108, 1890), cerebral blood-flow 45 tioned behavioral information measuring part and performing
responses occurring after neuron activity have focused only calculation, control and memory operations, and utilizing
on the cerebral blood flow, and during more than 110 years, it near-infrared spectroscopy to evaluate biological function;
was not possible to selectively measure oxygen exchange and the aforementioned apparatus body is characterized in
inside the capillaries. that it has a controller for calculating, based on the light
(6) There was no quantitative method that did not depend 50 information from the aforementioned living body probe, a
on the quantification of hemoglobin. variety of parameters derived from two-dimensional dia
The present invention is for the purpose of solving the grams showing relationships between changes in oxyhemo
above-stated problems, and first, as the physiological mecha globin and changes in deoxyhemoglobin and two-dimen
nism whereby the blood vessels, namely, the capillaries, pro sional diagrams showing relationships between absolute
vide oxygen to tissue, anywhere in the tissue of the living 55 amounts of oxyhemoglobin and absolute amounts of deoxy
body, constructs a theory of oxygen exchange rotational hemoglobin, a behavioral information input part for entering
motion in the capillaries, in which the phenomenon of oxygen behavioral information measured by means of the aforemen
exchange between oxyhemoglobin and deoxyhemoglobin in tioned behavioral information measuring part; and a display
the red blood cells is considered to be a rotational motion. The part for performing various types of image displays based on
present invention takes as its object the provision of an appa 60 various parameters calculated by means of the aforemen
ratus for evaluating biological function, a method for evalu tioned controller and/or the behavioral information entered in
ating biological function, and a living body probe that make it the aforementioned behavioral information input part.
possible to take new physiological indexes related to oxygen The method for evaluating biological function is a method
exchange metabolism as their measurement target, by placing for evaluating biological function in which near-infrared
oxyhemoglobin and deoxyhemoglobin on rectangular coor 65 spectroscopy is utilized to evaluate biological function, using
dinates (polar coordinates), from this theory of rotational an apparatus for evaluating biological function that has a
motion. plurality of living body probes provided with light-emitting
 US 8,406,838 B2
7 8
elements for irradiating light to specified sites of a living body invention, it is possible to judge whether the probe location is
and light-receiving elements for receiving and detecting light really able to properly select a cerebral gyrus. Because of this,
exiting the living body, a behavioral information measuring even if the channels are mounted somewhat roughly, it is
part for measuring behavioral information of the aforemen possible to accurately locate or select sites, for example, sites
tioned living body, and an apparatus body for entering light related to brain function, from on the head, and muscle func
information detected by means of the aforementioned living tion from the skin surface.
body probe and behavioral information measured by means (3) By arranging the living body probes according to the
of the aforementioned behavioral information measuring shape and size of the cerebral gyri and Sulci, it becomes
part, and performing calculation, control and memory opera possible to evaluate biological function with a high degree of
tions, and utilizes near-infrared spectroscopy to evaluate bio 10
precision.
logical function; (4) Tissue functional response can be detected even at
and it is characterized in that it has
(1) a step whereby light-emitting elements and light-receiv differences of milliseconds, without relying on peak times of
ing elements of living body probes are placed on a living blood response and the like.
body, and 15 (5) Integral values of response times (RT) in units of mil
(2) a step whereby light from the aforementioned light-emit liseconds can be utilized to acquire and display images of site
ting elements of the living body probes is irradiated to a information that is dependent on behavioral data, to acquire
living body, and and display graphically information that is dependent on net
(3) a step whereby, based on light information detected by the works between sites, and so on.
aforementioned light-receiving elements of the living body (6) Because the method does not depend on the detection
probes, selection or adjustment is made among light-emit sensitivity of each channel, image display distortion is elimi
ting element/light-receiving element combinations in each nated.
of the channels formed by the aforementioned living body (7) It can be utilized to extract information in inactive
probes, based on specified criteria, and thinking time, and, to measure thinking time between the task
(4) a step whereby, based on light information detected by the 25 presentation period and the implementation period during
aforementioned living body probes, selection or adjust conversation, writing and the like, independent of artifacts of
ment is made among combinations of the aforementioned movement, to evaluate learning effectiveness.
channels, based on specified criteria, and (8) Accurately selected data can be used for signal process
(5) a step whereby baseline data is measured from light infor ing, as a simple and convenient interface with the living body.
mation detected by means of the aforementioned living 30
Phenomena occurring simultaneously with the behavior
body probes with a living body at rest, and data analysis period, the stimulus period and the like, which are difficult to
and data display are performed, and observe from fMRI and PET blood flow measurements and
(6) a step whereby task presentation data is measured from from magnetoencephalograms, electroencephalograms and
light information detected by the aforementioned living the like, can be observed quantitatively.
body probe when a task is presented to the living body, and 35
(9) It benefits medicine not only as a way of measuring
data analysis and data display are performed.
The living body probe of the present invention is charac brain function, but also as a way to improve the quality of
terized in that it is used in the aforementioned apparatus for education/learning and thinking in daily life. For example, it
evaluating biological function. is possible to observe and investigate how oxygen consump
The living body probe mounting device of the present 40 tion and Supply responses can be supported in order to
invention is characterized in that the aforementioned living improve the effectiveness of education, prevention of aging,
body probes are installed on and retained by a mesh-like physical therapy, exercise and daily life.
stretchable retaining material. (10) It also becomes possible to evaluate the presence of
The living body probe support device of the present inven changes in function or a disability from the Surface, with a
tion is characterized in that it has retaining rings for holding 45 high degree of precision.
the aforementioned living body probes, and a ring Support (11) The effect on signals of motion artifacts (a cause of
frame for movably Supporting those retaining rings. distortion of actual data from the measurement target, by
The living body probe mounting accessory of the present movement of the muscles or the body) can be reduced.
invention is a living body probe mounting accessory for aid (12) Regions and time periods accompanying blood oxy
ing in mounting the aforementioned living body probes on the 50
gen exchange that are dependent on oxygen consumption and
head, and it is characterized in that it is made from a net-like oxygen Supply can be differentiated, rotational energy can be
material formed spaced at fixed intervals along lines parallel calculated, and a variety of image displays that are dependent
to the line connecting the outer eyelid and the outer ear canal on oxygen exchange rate (oxygen exchange angle) and total
and the line connecting the outer ear canal and the parietal hemoglobin can be performed.
line, respectively, and measuring marks are displayed on the 55
(13) It becomes possible to evaluate interrelationships of
surface of the aforementioned net-like material.
metabolism, blood vessel control and the like between living
Effects of the Invention body tissues.
(14) It becomes possible to improve S/N ratios and take
The present invention has the following excellent effects. 60 measurements independent of the amount of change, even
(1) Because two types of selection and adjustment can be when the changes in all the hemoglobins that are indexes of
performed to reduce variation within and between channels oxygen metabolism are weak.
using a variety of parameters (indexes), it becomes possible to (15) Oxygen metabolism in the capillaries can be measured
evaluate biological function to a high degree of precision. quantitatively. A quantitative imaging method for oxygen
(2) With conventional techniques, images were displayed 65 exchange in the capillaries can be realized.
with uniform distances between probes, conversely ignoring (16) It becomes possible to separate the FORCE effect and
the shape of the measurement target, but with the present the “Watering-the-garden” effect.
 US 8,406,838 B2
10
It is an apparatus that is capable of judging the strength of are placed is flat, and (C) an example in which a lens Support
tissue oxygen activity by means of differences in FORCE member is established for Supporting a lens inside the tip of a
effect. living body probe.
FIG. 10. A two-dimensional diagram showing polar coor
dinates (rectangular coordinates) with change in oxyhemo
is a late phase formula from PET that applies to the blood globin AHbO2 as the X-axis (horizontal axis) and change in
vessels, and it does not apply for oxygen activity in the cap deoxyhemoglobin AHb as the y-axis (vertical axis), and
illaries. with absolute value of oxyhemoglobin (HbO, (concentra
Namely, if the late phase is considered to be the oxygen tion: mol/l) as the X-axis (horizontal axis) and absolute value
Supply time period, this formula does not represent oxygen 10
of deoxyhemoglobin Hb as the Y-axis (vertical axis).
consumption. FIG. 11(A) is a schematic drawing showing the relation
(17) NIRS imaging differentiates the brain functional Vox ship between a K-ratio diagram and actual neuronal activity
els of two light functional voxels. and capillary oxygen exchange activity, and (B) and (C) are
Namely, it separates out voxels where oxygen exchange is graphs showing changes in HbO in different regions.
taking place (FORCE effect) and voxels where oxygen 15
FIG. 12. A graph that shows schematically the relationship
exchange is not taking place (Watering-the-garden effect).
Previously, high oxygen exchange voxels (FORCE effect) between oxygen exchange rate and the capillaries and the
and low oxygen exchange Voxels (Watering-the-garden veins.
effect) were mixed together, but the present invention makes FIG. 13. A conceptual explanation of a two-dimensional
it possible to differentiate them. diagram showing the various events.
(18) Time series pertaining to the passage time through the FIG. 14. A conceptual explanation of a two-dimensional
capillaries for red blood cells can be measured at a plurality of diagram showing the amplitude of fluctuation at rest: (A) is an
sites. example of a small amplitude, and (B) is an example of a large
(19) Oxygen exchange in the capillaries can be selectively amplitude.
measured. 25 FIG. 15. (A) and (B) are graphs showing relationships
(20) Quantification methods and quantitative imaging between the K-ratio and the E-ratio.
methods independent of the quantification of hemoglobin are FIG. 16. (A) is a graph showing changes in ScC) for all the
possible. channels, and (B) is a graph explaining the theoretical for
(21) By taking into consideration the polar coordinates mula using vectors of OxyHb, DeoxyHb, thb and ScC.
from two-dimensional diagrams, quadrant shift imaging 30 FIG. 17. (A)-(D) are graphs showing changes over time in
methods and Scalar change imaging methods, utilizing vec the four component vectors: oxyhemoglobin, deoxyhemo
tors and scalars, are possible. globin, total hemoglobin and oxygen saturation.
(22) When blood is utilized in fMRI, PET and the like, FIG. 18. (A) and (B) are graphs explaining the moment of
errors in functional evaluation arising from intermixed inertia on two-dimensional diagrams with oxygen Saturation
venous components can be identified and avoided in func 35 as the X-axis and total hemoglobin as the Y-axis; (A) is a
tional imaging. graph explaining the amount of change in kinetic energy
accompanying the phenomenon of oxygen exchange in the
BRIEF DESCRIPTION OF THE DRAWINGS capillaries; and (B) is a graph explaining the absolute kinetic
energy accompanying the phenomenon of oxygen exchange
FIG. 1. Characteristic graphs showing changes in hemo 40 in the capillaries.
globin concentration over time; (A) shows predominantly FIG. 19. A conceptual explanation of a two-dimensional
venous data and (B) shows predominantly capillary data. diagram showing a shifting locus of centroid coordinates G.
FIG. 2. A block diagram showing the configuration of an FIG. 20. A conceptual explanation of a two-dimensional
apparatus for evaluating biological function of the present diagram showing a shifting locus of center of rotation C.
working embodiment. 45 FIG. 21. An explanatory drawing showing the correlation
FIG. 3. FIG. 3(A) is a perspective view showing a living between amplitude of fluctuation and measured voxel size.
body probe, and (B) is a bottom view thereof. FIG. 22. (A) and (B) are graphs showing the slopes for
FIG. 4(A) is an explanatory drawing showing living body changes in State between at rest and during activity, for two
probes arranged on a mounting Strip, and (B) is an explana sites.
tory drawing showing amounting strip mounted on the side of 50 FIG. 23. Graphs showing (A) change in each of the hemo
the head. globins, (B) time course of the K-ratio, (C) time course of the
FIG. 5(A) is an explanatory drawing showing a situation in k-angle, (D) time course of the L-value, and (E) two-dimen
which a pair of living body probes is placed perpendicular to sional changes in the K-ratio.
the centerline of a gyrus, between Sulci, and (B) is an explana FIG. 24. Explanatory spatiotemporal displays of actual
tory drawing showing a situation in which they are placed 55 measured data, showing (A) change in oxyhemoglobin, (B)
along the centerline of a gyrus, between Sulci. change in deoxyhemoglobin, (C) change in total hemoglobin,
FIG. 6. An explanatory drawing showing an example dis (D) K-ratios, (E) k-angles, (F) L-values.
played on a monitor of the angles formed between the direc FIG. 25. Graph of time distribution maps of changes in
tion of living body probes placed in a plurality of sites on the hemoglobin (Hb) and changes in capillary oxygen saturation.
brain Surface and the direction of a gyrus (probe angle) 60 FIG. 26. Graphs displaying cumulative oxyhemoglobin
FIGS. 7(A)-(D) are explanatory drawings showing changes based on changes in oxyhemoglobin for two sites.
examples of living body probe arrangements. FIG. 27. Shows graphs displaying changes in oxyhemo
FIGS. 8(A)-(E) are explanatory drawings showing globin and cumulative oxyhemoglobin changes, showing (A)
examples of multilayer probes. a FORCE effect region, and (B) a Watering-the-garden effect
FIG.9. Cross-sectional views showing (A) a case in which 65 region.
the surface where the living body probes are placed is curved, FIG. 28. (A) is a graph showing time course changes in
(B) a case where the surface on which the living body probes tEb. (B) is a graph showing time course changes in the dif
 US 8,406,838 B2
11 12
ferentials of thb, and (C) is a two-dimensional diagram of the dimensional diagrams of OxyHb and DeoxyHb, and the rela
differentials of thb and their differentials. tionships between the respective vectors are displayed.
FIG. 29. Graphs displaying time courses of summed data FIG. 46. Graphs explaining the separation of the FORCE
fortHb and ScC) from a desired starting point, namely, cumu effect and the Watering-the-garden effect.
lative thb changes and cumulative ScC) changes. FIGS. 47(A)-(C) are drawings explaining arrangements of
FIG. 30. Graphs showing slopes R that are completely living body probes utilizing the centerline.
different at rest and during activity for regions displaying FIG. 48(A) is a drawing explaining the divisions of the
different amounts of change in ScC), but that have a high cerebrum; (B) is a drawing explaining an example of a fan
correlation coefficient.
10
shaped probe arrangement; and (C) and (D) are drawings
FIG. 31. Graphs showing slopes R that are completely explaining examples of horizontal probe arrangements.
different at rest and during activity for regions displaying FIGS. 49(A) and (B) are drawings explaining the arrange
different amounts of change in thb, but that have a high ment of living body probes in diamond-shaped basic shapes;
correlation coefficient. (C) and (D) are drawings explaining examples of living body
FIG. 32. Flowchart explaining a method for evaluating 15 probes arranged in diamond-shaped applications.
biological function of a working embodiment of the present FIGS. 50(A)-(C) are drawings explaining examples of liv
invention. ing body probes arranged in radially-shaped applications.
FIG. 33. (A) is a two-dimensional diagram showing the FIG. 51(A) is an explanatory drawing of a view from the
relationship between behavior time RT and integral values, back of a human head; (B) is a drawing explaining the inter
and (B) is a two-dimensional diagram showing the relation section of the line joining the left and right outer ear canals
ship between integral values measured from a plurality of and the line joining the glabella and the torus occipitalis.
sites in a desired time period. FIG. 52(A) is an image display, with living body probes
FIG.34 is L-value maps in which identification of learning arranged in a lattice shape, of K-ratios and L-values from the
patterns is extracted in time series from brain site informa periphery of the left and right motor areas at a point 22.8
tion; (A) is a screen showing cognitive response; (B) is a 25 seconds in the midst of lifting a 14 kg dumbbell; and (B) is an
screen showing thought-associated brain response; and (C) is image display of k-angles and L-values from the periphery of
a screen showing behavior-related brain response. the left and right motor areas at a point 22.8 seconds in the
FIG.35. A two-dimensional diagram with time as the hori midst of lifting a 14 kg dumbbell.
Zontal axis and integrals as the vertical axis; (A) is the infor FIG. 53(A) is a graph displaying K-spiral motion verti
mation input period; (B) is the thought period; and (C) is the 30 cally, and (B) is a graph displaying it horizontally.
output period. FIG. 54(A) is a diagram explaining K-spiral motion three
FIG. 36. (A)-(C) are examples of displays in which sites are dimensional display evaluation criteria, (B) is a diagram
joined by lines drawn between them to show association explaining T-spiral motion three-dimensional display evalu
between sites during each behavior period. ation criteria, (C) is a diagram explaining H-spiral motion
FIG. 37. An explanatory figure showing an example in 35 three-dimensional display evaluation criteria, and (D) is a
which variation in target sites in the right brain and the left diagram explaining I-spiral motion three-dimensional dis
brain (laterality) is displayed in time series. play evaluation criteria.
FIG.38 is a graph explaining the fact that the behavior time FIGS. 55(A)-(D) are three-dimensional diagrams showing
RT and maximum and minimum peak times of NIRS-mea the K-spiral motion of channels 4, 7, 9 and 11; they are
Sured parameters do not match. 40 examples in which lines are entered for Hb and HbO.
FIG. 39. An explanatory drawing showing an example in FIGS. 56(A)-(D) are three-dimensional diagrams showing
which a plurality of living body probes are randomly arranged the K-spiral motion of channels 4, 7, 9 and 11; they are
(spaced) with respect to the measurement point. examples in which vertical lines are entered along the time
FIG. 40 is an explanatory drawing showing the results aX1S.
when the respective maximum values for left and right net 45 FIG. 57 is a graph showing changes in the L-angle when a
work share and both-sides network share are taken as 1.0 subject lifted dumbbells in the order of 1 kg, 4 kg and 7.5 kg.
(100%); a maximum equilateral triangle is formed from these FIG.58 is a graph showing the relationship between wave
three points; the area formed by joining those points is taken length and absorbance.
as the total network share area; and time series data is mea FIG. 59 is a graph of changes in absorption coefficient at
Sured by segment. 50 830 nm and changes in absorption coefficient at 780 nm
FIG. 41 is explanatory figures showing (A) k-angle quad plotted in two dimensions by task.
rants, and (B) an example of a functional image display of FIG. 60 is a graph of changes in absorption coefficient at
quadrants and L-values. 830 nm and changes in absorption coefficient at 780 nm
FIG. 42 is explanatory drawings of k-angle quadrant spa plotted in two dimensions by site.
tiotemporal displays (A) when writing hiragana, (B) when 55 FIG. 61 is a graph showing time series changes in light path
writing kanji, and (C) when the Subject does not know the length (PL) when a task is presented.
kanji. FIG. 62 shows waveforms for oxyhemoglobin (O) and
FIG. 43 is graphs showing a case when indexes are com deoxyhemoglobin (D); (A) shows a phase difference of 0
pared with respect to the different tasks of lifting 7 kg as task degrees; (B), a phase difference of 90 degrees; and (C), a
B and lifting 14 kg as task A. 60 phase difference of 180 degrees.
FIGS. 44(A) and (B) are graphs concerning brain data FIG. 63 is a graph explaining the oxygen exchange phase
when a subject lifted 7 kg and 14 kg dumbbells for a desired difference angle.
time, when ScC)=(OxyHb-DeoxyHb) and thb=(OxyHb+ FIG. 64 is a graph explaining the absolute oxygen
DeoxyHb) are displayed in real time. exchange phase difference angle.
FIGS. 45(A) and (B) are graphs concerning brain data 65 FIGS. 65(A) and (B) are explanatory drawings showing the
when the subject lifted 7 kg and 14 kg dumbbells for a desired relationships between total hemoglobin and fluctuation for
time, when the data are displayed simultaneously in two different measurement targets.
 US 8,406,838 B2
13 14
FIG. 66(A) is a graph displaying fluctuation for a plurality FIG. 86(A) is a block diagram showing an example in
of measurement regions on polar coordinates, and (B) is a which an apparatus for evaluating biological function of a
graph displaying vectors. working embodiment of the present invention is connected
FIG. 67 is a graph displaying oxygen exchange rotational with a pressure application device for applying stimulus
motion of a plurality of measurement regions on polar coor (pressure) to the brain. FIG. 86(B) is a graph showing the
dinates. results of measuring changes in each kind of Hb for each of a
FIG. 68 is graphs showing changes in total hemoglobin at number of channels (the numbers show the channel num
measuring sites 1 and 2. bers), when pressure is applied to the right arm by means of a
FIG. 69 shows a graph every each channel which added 10
pressure application device.
time series data of a change of total Hb which synchronized to FIG. 87(A) is a lateral view showing a modified example of
respiratory cycle. a living body probe, and (B) is a front view thereof.
FIG. 70 is a graph showing time-series correlations for FIG. 88 is a drawing explaining a measuring technique for
channel 4 and channel 17. the inferior temporal gyrus.
FIG. 71 is shows a graph every each channel which added 15 FIG. 89 is a perspective view showing a living body probe
time series data of a change of HbO, which synchronized to mounting device 26 of a working embodiment of the present
respiratory cycle. invention.
FIG.72 is shows a graph every each channel which added FIGS. 90(A)-(C) are drawings explaining a living body
time series data of a change of Hb which synchronized to probe mounting accessory of a working embodiment of the
respiratory cycle. present invention.
FIG. 73 shows a graph every each channel which added FIG. 91(A) is a plan view showing a living body probe
time series data of a change of (HbO-Hb) which syn Support device of a working embodiment of the present inven
chronized to respiratory cycle. tion; (B) is a perspective view showing a retaining ring; (C) is
FIG. 74 is a graph in which heartbeat and respiratory cycle a cross-sectional view along line c-c of (A); and (D) is a
variation are spatiotemporally displayed for each channel. 25 cross-sectional view along line d-d of (A).
FIG. 75 shows a graph every each channel which added FIGS. 92(A)-(D) are plan views showing modified
time series data of a change of total Hb which synchronized to examples of living body probe Support devices.
heartbeat. FIGS. 93(A) and (B) are drawings explaining the indepen
FIG. 76 shows a graph every each channel which added dence and interconnectedness of light functional Voxels cor
time series data of a change of HbO, which synchronized to 30 responding to a probe arrangement.
heartbeat. FIGS. 94(A) and (B) are drawings explaining the indepen
FIG. 77 shows a graph every each channel which added dence and interconnectedness of light functional voxels cor
time series data of a change of Hb which synchronized to responding to a probe arrangement.
heartbeat. FIGS. 95(A)-(D) are drawings explaining the fourthought
FIG. 78 shows a graph every each channel which added 35 patterns of the human brain.
time series data of a change of (HbO-Hb) which syn
chronized to heartbeat. EXPLANATION OF THE SYMBOLS
FIG. 79 is graphs showing the brain respiratory synchro
nization component for site 1 and site 2: their differentials, 1: Living body probe
brain respiratory synchronization velocity; and their further 40 1a: Light-emitting element
differentials, brain respiratory acceleration. 1b: Light-receiving element
FIG.80 is graphs showing the brain heartbeat synchroni 2: Behavioral information measuring part
zation component for site land site 2: their differentials, brain 3 : Apparatus body
heartbeat synchronization velocity; and their further differ 4 : Light intensity adjustor
entials, brain heartbeat acceleration. 45 5 : Selector-adjustor
FIG. 81 is a two-dimensional diagram showing the corre 6 : Signal amplifier
lation between behavioral information (the meaning of writ 7: A/D converter
ten characters, the length of a line, scores, etc.) and various 8: Controller
parameters (integral values, amounts of change) during the 9: Memory
same time period. 50 10: Display part
FIGS. 82(A) and (B) are graphs showing cumulative 11: Sampling speed adjuster
summed values for problem response time (RT) at desired 12: Behavioral information input part
sites; (A) is a graph of problems correctly answered by one 13: Mounting strip
individual, and (B) is a graph of problems incorrectly 14: Sulcus
answered by one individual. 55 15: Gyrus
FIG. 83(A) is a graph showing cumulative summed data for 20: Lens
all those taking a test, by problem; (B) is a graph showing the 21: Lens Support member
degree of individual effect, by examinee. 22: Pressure application device
FIG. 84(A) is a graph showing the relationship between the 23: Protective cover
electrocardiogram and changes in parameters of regions 60 24: Soft material
dominated by the left and right anterior cerebral arteries in the 25: Outer ear canal
case of normal brain vessels, and (B) is a graph showing the 26: Living body probe mounting device
relationship between the electrocardiogram and changes in 27: Living body probe mounting accessory
parameters of regions dominated by the left and right anterior 28: Retaining ring
cerebral arteries in the case of an abnormal brain vessel. 65 29: Ring support frame
FIG. 85(A) shows a case in which the spread of L-values is 30: Living body probe support device
Small; and (B), a case in which the spread of L-values is large. CL: Centerline