pdf hosted at the radboud repository of the radboud university nijmegen · electromagnetic waves we...
TRANSCRIPT
PDF hosted at the Radboud Repository of the Radboud University
Nijmegen
The following full text is a publisher's version.
For additional information about this publication click this link.
http://hdl.handle.net/2066/19136
Please be advised that this information was generated on 2020-07-11 and may be subject to
change.
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QUANTITATIVE NEAR-INFRARED SPECTROSCOPY
IN HUMAN SKELETAL MUSCLE
METHODOLOGICAL ISSUES AND CLINICAL APPLICATION
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OUTLINE
Background Near-infrared spectroscopy
Quantitative NIRS measurements Venous occlusion method Arterial occlusion method Oxygen consumption Blood flow Venous oxygen saturation Half-recovery time Reoxygenation rate
NIRS measurements during exercise Sustained vs. rhythmic isometric exercise Arm vs. leg measurements
Aim of the thesis Thesis outline
Methodological issues Clinical application
INTRODUCTION
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BACKGROUND
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Fig. 1 The electromagnetic spectrum. Both frequency and wavelength are presented together with the most common applications.
AM Radio Band
Short Wave
TV and FM Radio Band
Infrared
Millimeter Waves, Telemetry
Microwaves, Radar
Gamma Rays
X-Rays
Ultraviolet
VisibleLight
AM Radio Band: radio, maritime com-
munication, and aircraft navigation.
Short Wave: amateur radio, inter-
national broadcast, fixed and mobile
communications, government radio; in-
cluding police, fire, forestry, highway,
and railroad services.
TV and FM Radio Band: television,
radio, fixed and mobile communi-
cations, amateur broadcast, govern-
ment and non-government signals,
satelite communication and Global
Positioning System (GPS).
Microwaves, Radar: microwave ovens,
radio navigation.
Millimeter Waves, Telemetry: variety of
experimental, government and
amateur purposes in communication.
Infrared: near-infrared spectroscopy ,
pulse oximetry, Green-house effect,
radiation from hot objects, infrared ear
thermometers, photography.
Visible Light: these are the only
electromagnetic waves we can see.
Each color has a different wavelength.
Red the longest, violet the shortest. All
waves together make white light.
Ultraviolet: sunburn, UV-therapy, in-
volved in the production of vitamin D,
astronomy.
X-Rays: medical images, airport
security, astronomy.
Gamma-rays: cancer radiation therapy,
astronomy.
Wav
elen
gth
(m)
10-15
10-14
10-13
10-12
10-11
10-10
10-9
10-8
10-7
10-6
10-5
10-4
10-3
10-2
10-1
100
101
102
103
104
105
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quen
cy (
Hz) 103
104
105
106
107
108
109
1010
1011
1012
1013
1014
1015
1016
1017
1018
1019
1020
1021
1022
1023
CHAPTER 1
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Fig. 2 Schematic presentation of the set-up with the spectrophotometer emitting light of 3 wavelengths (770, 848, and 901 nm) The light is transported into the tissue by an optical fibre (optode). The light that is detected by the receiver is thought to describe a banana-shape travelling through the tissue [Cui et al. 1991]. Typically, the interoptode distance used in this thesis was 35 and 50 mm.
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Fig. 3 Changes in lactate and ammonia during the ischemic forearm test. Patients with myoadenylate deficiency (MAD) lacked ammonia production while patients with myophosphorylase deficiency (McArdle's disease) lacked lactate production. mitochondrial myopathies could not be discriminated from the controls.
∆lactate(mmol⋅l-1)
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mitochondrial myopathies
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Fig. 4 Extinction coefficients of adult oxyhaemoglobin (O2Hb) and deoxyhaemoglobin (HHb) as determined by Wray et al. [Wray et al. 1988]. Dotted lines represent the 3 wavelengths used (770, 848, and 901 nm).
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Fig. 5 Near-infrared spectrophotometer (Oxymon, Biomedical Engineering Department, University of Nijmegen, NL) as has been used in this study for the measurement of tissue oxygenation and haemodynamics in human skeletal muscle.
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Fig. 7 Quantitative NIRS measurements during A) venous occlusion and B) arterial
occlusion. During venous occlusion, blood flow (BF), muscle oxygen consumption
( 2OVm � ), and venous saturation (SvO2) can be calculated. Using arterial occlusion and its
recovery phase, it is possible to calculate 2OVm � , reoxygenation rate (∆O2Hb), and half-
recovery times (t50) of the signals. �
450 460 470 480 490 500 510-2
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[O2H
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Fig. 8 Half-time recovery, calculated as A) the time needed for half recovery of O2Hb from maximum deoxygenation at the end of arterial occlusion or exercise to maximum re-oxygenation during hyperaemia, and B) the tau value derived from a mono-exponential curve-fit of O2Hb recovery as is standard for calculation of PCr resynthesis with 31P-MRS.
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Fig. 9 Individual NIRS O2Hb, HHb, and tHb signals during exercise, arterial occlusion, and recovery. Rhythmic isometric handgrip exercise was performed at 70% of the subject's maximum voluntary contraction force (MVC). Rhythmic changes, corresponding to muscle contraction and relaxation are clearly visible in the NIRS signals during exercise.
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SUMMARY
The aim of this study was to investigate local oxygen consumption ( 2OVm � ) and forearm blood flow (FBF) in resting and exercising
muscle by use of near-infrared spectroscopy (NIRS) and to compare the results with the global 2OVm � and FBF derived from the well-
established Fick-method and plethysmography. 2OVm � was derived
from 1) NIRS using venous occlusion, 2) NIRS using arterial occlusion, and 3) the Fick-method ( ( )Fick2 OVm � ). FBF was derived from
1) NIRS and 2) strain-gauge plethysmography. Twenty-six healthy subjects were tested at rest and during sustained isometric handgrip exercise. Local variations were investigated with two independent and simultaneously operating NIRS systems at two different muscles and two measurement depths. 2OVm � increased more than fivefold in the
active flexor digitorum superficialis muscle, and it increased 1.6 times in the brachioradialis muscle. The average increase in ( )Fick2 OVm � was
twofold. FBF increased 1.4 times independent of the muscle or the method. It is concluded that NIRS is an appropriate tool to provide information about local 2OVm � and local FBF because both place and
depth of the NIRS measurements reveal local differences that are not detectable by the more established, but also more global, Fick method.
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NIRS PERFORMANCE IN HUMAN SKELETAL MUSCLE
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NIRS PERFORMANCE IN HUMAN SKELETAL MUSCLE
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Method NIRS NIRS NIRS Plethysmo
-graphy
POX Blood gas
analysis
Intervention Venous
occlusion
Arterial
occlusion
Venous
occlusion
Venous
occlusion
Arterial
pulse
Venous
samples
Variables: CaO2 CvO2
FBFNIRS FBFPleth (a-v)O2diff
( )VONIRS 2OVm �
( )AONIRS2OVm � ( )Fick2OVm �
Fig. 1. Protocol (A) and measurements (B) as performed by each subject. Venous and arterial occlusion (VO and AO, respectively) are applied at rest and during sustained isometric handgrip exercise at 10% of the subject’s maximal voluntary contraction force (10%MVC). BS = blood sample. See METHODS for a detailed description of the protocol. From this protocol, oxygen consumption was calculated with NIRS during VO
( ( )VONIRS2 OVm � ) and during AO ( ( )AONIRS2OVm � ). Forearm blood flow was calculated during
VO with NIRS (FBFNIRS) and with plethysmography (FBFPleth). Oxygen consumption
derived from Fick ( ( )Fick2OVm � ) was obtained by the combination of plethysmography,
pulse oximetry (POX) and blood sampling. CaO2 = arterial O2 content, CvO2 = venous O2 content, (a-v)O2diff = arterio-venous O2 difference.
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BS
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BS BS BS
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Table 1. Correlation between ATT and ( )AONIRS2OVm � in the FDS and BR
FDS IO35 FDS IO50 BR IO35
ATT (mm) 2.2 ± 0.8
(1.3-4.5)
2.2 ± 0.8
(1.3-4.5)
2.6 ± 0.5
(1.8-3.7)
Spearman r -0.13 0.11 -0.20
P 0.52 0.61 0.31
Values are mean ± SD (range) for adipose tissue thickness (ATT). Spearman correlation coefficient (r) and P values are given for the three
near-infrared spectroscopy (NIRS) local muscle O2 consumption ( 2OVm � )
measurements. FDS, flexor digitorum superficialis muscle; BR, brachio-radialis muscle; IO35 and IO50, interoptode distances of 35 and 50 mm, respectively.
CHAPTER 2
� 40
Table 2. Reproducibility of 2OVm � and FBF during three consecutive venous occlusions
VO-1 VO-2 VO-3 Comparison P value CV (%)
( )VONIRS 2OVm � FDS IO35
n = 24
0.09 ± 0.04 0.08 ± 0.04 0.08 ± 0.04 Overall
VO-3 vs. VO-1
VO-3 vs. VO-2
VO-2 vs. VO-1
*
*
NS
**
P = 0.01
P < 0.05
P > 0.05
P < 0.01
30.6
FDS IO50
n = 20
0.08 ± 0.04 0.08 ± 0.04 0.07 ± 0.04 Overall NS 25.4
BR IO35
n = 26
0.14 ± 0.09 0.14 ± 0.11 0.13 ± 0.10 Overall NS 23.3
FBFNIRS FDS IO35
n = 25
0.76 ± 0.33 0.70 ± 0.39 0.71 ± 0.35 Overall NS 28.6
FDS IO50
n = 21
0.61 ± 0.28 0.59 ± 0.34 0.54 ± 0.28 Overall NS 30.3
BR IO35
n = 26
1.41 ± 1.01 1.40 ± 1.09 1.44 ± 1.11 Overall NS 20.4
FBFPleth n = 24 2.07 ± 0.86 2.01 ± 0.73 2.07 ± 0.71 Overall NS 16.7
Values are mean (±SD) for 2OVm � (mlO2⋅min-1⋅100g-1) and forearm blood flow (FBF; ml⋅min-1⋅100ml-1).
First, second, and third venous occlusions are represented by VO-1, VO-2, and VO-3, respectively. Number of subjects (n) varies due to missing values in either VO-1, VO-2 or VO-3. CV, coefficient of variation. *P ≤ 0.05; **P ≤ 0.01; NS, not significant.
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NIRS PERFORMANCE IN HUMAN SKELETAL MUSCLE
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Table 3. 2OVm � values measured by NIRS during arterial occlusion vs. venous occlusion
( )AONIRS2OVm � , ( )VONIRS2OVm � ,
mlO2⋅min-1⋅100g-1 mlO2⋅min-1⋅100g-1 P value
Rest FDS IO35 0.11 ± 0.03
FDS IO50 0.09 ± 0.03 0.08 ± 0.04 NS P = 0.04
BR IO35 0.13 ± 0.05 0.14 ± 0.10 NS P = 0.51
Exercise FDS IO35 0.58 ± 0.27 0.21 ± 0.12 ** P < 0.01
FDS IO50 0.55 ± 0.22 0.19 ± 0.10 ** P < 0.01
BR IO35 0.20 ± 0.09 0.24 ± 0.21 NS P = 0.30
Values are means ± SD; n = 22 for FDS IO35; n = 26 for FDS IO50 and BR IO35. No P value was
calculated for FDS IO35 at rest because ( )VONIRS2OVm � was not reproducible. ( )AONIRS2OVm � , 2OVm �
measured by arterial occlusion. To protect against a type I error, an α of 0.01 was chosen, **P ≤ 0.01.
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Fig. 2. Average and SD for NIRS 2OVm � vs. NIRS FBF showing an increased 2OVm � in
the active flexor digitorum superficialis muscle (FDS) during isometric handgrip exercise with interoptode distances of 35 and 50 mm (IO35 and IO50, respectively) compared with the relative inactive brachioradialis muscle (BR). Circles represents resting values, and triangles represents values during exercise. Significant differences are shown in Table 4.
mVO2 (mlO2⋅min-1⋅100g-1)
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
FB
F (
ml⋅ 1
00m
l-1⋅ m
in-1
)
0.0
0.5
1.0
1.5
2.0
2.5
3.0
3.5
4.0
4.5
5.0
FDS IO35
FDS IO50
BR IO35
NIRS PERFORMANCE IN HUMAN SKELETAL MUSCLE
� 43
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Table 4. 2OVm � and FBF values at rest and during sustained isometric handgrip exercise at 10%
maximum voluntary contraction
2OVm � , mlO2⋅min-1⋅100g-1 FBF, ml⋅min-1⋅100ml-1
Rest Exercise Rest Exercise
NIRS FDS IO35 0.11 ± 0.03 0.59 ± 0.27 † 0.72 ± 0.32 0.98 ± 0.46 †
NIRS FDS IO50 0.09 ± 0.03 * 0.55 ± 0.22 † 0.57 ± 0.26 * 0.81 ± 0.47 *, †
NIRS BR IO35 0.13 ± 0.05 0.20 ± 0.09 *, † 1.42 ± 1.04 * 2.18 ± 1.98 *, †
Fick/pleth. 0.15 ± 0.06 * 0.30 ± 0.12 *, † 2.06 ± 0.70 * 2.98 ± 1.26 *, †
Values are means ± SD. *Significantly different (P ≤ 0.01) from FDS IO35; †significant difference
(P ≤ 0.01), rest vs. exercise.
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SUMMARY
The aim of this study was to investigate the performance of in vivo quantitative near-infrared spectroscopy (NIRS) in skeletal muscle at various workloads. NIRS was used for the quantitative measurement of O2 consumption ( 2OVm � ) in the human flexor digitorum superficialis
muscle at rest and during rhythmic isometric handgrip exercise in a broad range of work intensities (10-90% MVC = maximum voluntary contraction force). Six subjects were tested on three separate days. No significant differences were found in 2OVm � measured over different
days with the exception of the highest workload. The within-subject variability for each workload over the three measurements days ranged from 15.7 - 25.6% and did not increase at the high workloads. 2OVm �
was 0.14 ± 0.01 mlO2⋅min-1⋅100g-1 at rest and increased roughly 19 times to 2.68 ± 0.58 mlO2⋅min-1⋅100g-1 at 72% MVC. These results show that local muscle oxygen consumption at rest as well as during exercise at a broad range of work intensities can be measured reliably by NIRS, applied to a uniform selected subject population. This is of great importance since direct local measurement of 2OVm � during
exercise is not possible with the conventional techniques. The method is robust enough to measure over separate days and at various workloads and can, therefore, contribute to a better understanding of human physiology in both the normal and pathological state of the muscle.
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INTRODUCTION
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RESULTS
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Fig. 1. Raw NIRS signal during 1 min of rhythmic isometric handgrip exercise at 20% of the maximum voluntary contraction force (MVC) followed by 45 s of arterial occlusion. O2 consumption was calculated from the linear decrease in oxyhaemoglobin (O2Hb) immediately after the start of the occlusion and from the linear decrease in Hbdiff ([Hbdiff] = [O2Hb] – [HHb]) (not shown). The sum of [O2Hb] and [HHb] reflects the total amount of haemoglobin ([tHb]) and changes in tHb can be interpreted as changes in blood volume in the tissue.
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Table 1. Mean (± SE) values for O2 consumption ( 2OVm � ) from Hbdiff at rest and during rhythmic
isometric handgrip exercise.
Rest 9% MVC 18% MVC 28% MVC 36% MVC 44% MVC 61% MVC 72% MVC
Day 1 0.14 ± 0.01 0.38 ± 0.07 0.84 ± 0.25 1.31 ± 0.44 1.52 ± 0.51 1.85 ± 0.63 2.45 ± 0.79 2.54 ± 0.73
Day 2 0.15 ± 0.02 0.43 ± 0.09 0.95 ± 0.23 1.48 ± 0.37 1.83 ± 0.43 2.16 ± 0.65 2.68 ± 0.71 3.13 ± 0.59
Day 3 0.15 ± 0.02 0.41 ± 0.07 0.88 ± 0.25 1.46 ± 0.45 1.97 ± 0.56 2.14 ± 0.68 2.36 ± 0.60 3.06 ± 0.59
Avg 0.15 ± 0.01 0.41 ± 0.07 0.89 ± 0.24 1.42 ± 0.41 1.77 ± 0.49 2.05 ± 0.64 2.50 ± 0.69 2.91 ± 0.63
P-value 0.99 0.32 0.34 0.49 0.10 0.24 0.49 0.02 *
day 1 < day 2 day 1 < day 3
CV (%) 17.6 16.3 21.1 23.2 23.0 20.3 20.0 20.6
2OVm � in mlO2⋅min-1⋅100g-1. MVC = maximal voluntary contraction force, CV = coefficient of variation, n
= 6. *P ≤ 0.05 for differences between the three days.
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Table 2. Within-subject variability for 2OVm � from Hbdiff at rest and during isometric handgrip exercise at
9% and 72% of the maximal voluntary contraction force (MVC).
Rest 9% MVC 72% MVC
Subject I II III CV (%) I II III CV (%) I II III CV (%)
1 0.15 0.11 0.09 25.0 0.55 0.61 0.45 15.2 1.70 2.30 2.00 14.9
2 0.18 0.14 0.21 21.4 0.40 0.54 0.57 17.8 2.76 3.54 3.10 12.6
3 0.13 0.11 0.10 10.8 0.41 0.37 0.33 11.1 1.51 2.09 1.87 16.1
4 0.14 0.18 0.17 12.7 0.11 0.16 0.17 21.9 2.37 3.23 3.52 19.6
5 0.13 0.13 0.14 5.0 0.24 0.23 0.31 17.3 0.93 1.84 2.18 39.0
6 0.14 0.22 0.17 21.8 0.54 0.69 0.62 12.1 5.95 5.78 5.70 2.2
Avg 17.6 Avg 16.3 Avg 20.6
2OVm � in mlO2⋅min-1⋅100g-1. CV = coefficient of variation ((SD/mean)⋅100%), I = day 1, II = day 2, III = day 3.
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Fig. 3. Group mean (± SE) over three measurement days for muscle oxygen consumption
( 2OVm � ) values during arterial occlusion at rest and after isometric handgrip exercise at
various work intensities. Closed circles represent 2OVm � calculated from Hbdiff, open circles
represent 2OVm � calculated from O2Hb. *P ≤ 0.05, **P ≤ 0.01 and ***P ≤ 0.001 for differences
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0 10 20 30 40 50 60 70 80 90
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Table 3. Mean (± SE) values for resting O2 consumption ( 2OVm � ) from literature.
Method 2OVm �
Method 2OVm �
Holling 1939 Fick 0.11 De Blasi et al. 1992 NIRS 0.11 ± 0.02
Mottram 1955 Fick 0.23 ± 0.02 De Blasi et al. 1993 NIRS 0.05 ± 0.01
Hartling et al. 1989 Fick 0.14 ± 0.04 De Blasi et al. 1994 NIRS 0.10 ± 0.01
Van Beekvelt et al. 2001b Fick 0.15 ± 0.01 De Blasi et al. 1997 NIRS 0.06 ± 0.01
Wang et al. 1990 31P-MRS 0.17 Niwayama et al. 1999 NIRS 0.21 ± 0.01
Hamaoka et al. 1996 31P-MRS 0.16 ± 0.00 Van Beekvelt et al. 2001a NIRS 0.11 ± 0.01
Sako et al. 2001 31P-MRS 0.16 ± 0.00 Van Beekvelt et al. 2001b NIRS 0.11 ± 0.00
2OVm � data from various studies were converted to mlO2⋅min-1⋅100g-1 using 1.04 kg⋅L-1 for muscle
density and 22.4 L as the molar volume of gas assuming STPD conditions. 1 mol of O2 is assumed to synthesise 6 mol of ATP.
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SUMMARY
The influence of adipose tissue thickness (ATT) on in vivo near-infrared spectroscopy (NIRS) measurements was studied in the human flexor digitorum superficialis muscle at rest and during sustained isometric handgrip exercise. NIRS was used for the quantitative measurement of muscle O2 consumption ( 2OVm � ) and
forearm blood flow (FBF) in seventy-eight healthy subjects. Skinfold thickness ranged from 1.4 – 8.9 mm within the group. Resting 2OVm �
was 0.11 ± 0.04 mlO2⋅min-1⋅100g-1, and FBF was 1.28 ± 0.82 ml⋅100ml-1⋅min-1. There was a negative correlation (r = -0.70, P ≤ 0.01) indicating a decrease in 2OVm � with increasing ATT. 2OVm � in
the 10 leanest subjects appeared to be twice as high as that in the 10 subjects with the highest ATT. A poor correlation (r = 0.29, P ≤ 0.01) was found between ATT and FBF. The gender difference that we found for 2OVm � was due to the difference in ATT between female
and male subjects. No correlation was found between maximum voluntary contraction (MVC) force and 2OVm � nor between MVC and
ATT, indicating that the contraction force did not confound our results. These results show that ATT has a substantial confounding effect on in vivo NIRS measurements, and that it is essential to incorporate this factor into future NIRS muscle studies in order to justify comparisons between various groups. To facilitate such comparisons, upper and lower boundaries for normal values of 2OVm � and FBF in relation to
ATT are presented. �
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Fig. 1 Distribution of ATT for the 78 subjects. ATT is defined as skinfold thickness / 2. Data from male and female subjects are presented as stacked bars.
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ATT (mm)
0 1 2 3 4 5 6 7 8 9 10
Fre
quen
cy
0
2
4
6
8
10
12
14
16malefemale
CHAPTER 4
� 70
Table 1. Reproducibility of NIRS FBF and 2OVm � measurements during three consecutive occlusions
I II III CV (%)
FBF (ml⋅min-1⋅100ml-1) 1.26 ± 0.88 1.23 ± 0.78 1.34 ± 0.96 22.4
2OVm � (mlO2⋅min-1⋅100g-1) 0.12 ± 0.05 0.11 ± 0.04 0.10 ± 0.04 16.2
FBF was measured during venous occlusion, and 2OVm � during arterial occlusion. Values are means
± SD, and the coefficient of variance (CV) is given in each case. The first, second, and third occlusion are represented by I, II, and III, respectively.
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�Table 2. Correlation coefficients for the relationship between ATT and NIRS variables
ATT a b SE(a) SE(b) r P-value
Rest FBF 0.71 1.11 0.24 0.43 0.29 *
Rest 2OVm � 0.18 -0.14 0.02 0.01 -0.70 **
10% MVC 2OVm � 0.71 -0.54 0.10 0.18 -0.33 **
20% MVC 2OVm � 1.20 -0.99 0.14 0.26 -0.41 **
30% MVC 2OVm � 1.43 -1.18 0.19 0.36 -0.36 **
The relationship is defined by the equation: FBF or 2OVm � = a + b*log(ATT). Calculated values are
given for all variables; a, b, standard error (SE) of a and b, and r. *P ≤ 0.05; **P ≤ 0.01.
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Table 3. Values for 2OVm � and FBF at rest and during sustained isometric handgrip exercise for
female and male subjects separately
Female (33) Male (44) P-value
Rest FBF 1.46 ± 0.74 1.14 ± 0.86 0.159
Rest 2OVm � 0.08 ± 0.03 0.13 ± 0.03 **
10% MVC 2OVm � 0.31 ± 0.18 ## 0.53 ± 0.41 ## **
20% MVC 2OVm � 0.48 ± 0.33 ## 0.87 ± 0.54 ## **
30% MVC 2OVm � 0.52 ± 0.40 1.07 ± 0.75 ## **
2OVm � values are given in mlO2⋅min-1⋅100g-1, and FBF values in ml⋅min-1⋅100ml-1. Values are means ±
SD. Significance of differences: **P ≤ 0.01 for male compared with female subjects; ##P ≤ 0.01 for
differences in 2OVm � between two consecutive workloads.
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ADIPOSE TISSUE THICKNESS VERSUS NIRS
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Fig. 2 Correlation between log(ATT) and NIRS variables at rest. A) 2OVm � and B) FBF,
measured in 78 healthy subjects. Data from male (Ì) and female (Ä) subjects are shown separately.
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Log(ATT)0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
mV
O2
(mlO
2⋅ min
-1⋅ 1
00g-1
)
0.00
0.05
0.10
0.15
0.20
0.25
ATT (mm)
1.0 1.3 1.6 2.0 2.5 3.2 4.0 5.0 6.3 7.9 10.0
Log(ATT)
0.0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9 1.0
FB
F (
ml⋅ m
in-1
⋅ 100
ml-1
)
-1
0
1
2
3
4
5
6
ATT (mm)
1.0 1.3 1.6 2.0 2.5 3.2 4.0 5.0 6.3 7.9 10.0
FBF = 0.71 - 1.11*log(ATT)
r = 0.29
P = 0.01
mVO2 = 0.18 - 0.14*log(ATT)
r = -0.70
P ≤ 0.01
B
A
CHAPTER 4
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DISCUSSION
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ADIPOSE TISSUE THICKNESS VERSUS NIRS
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Fig. 3 Simplified schematic presentation of NIRS light penetration in relation to ATT (+skin) and muscle tissue in our subject with the greatest ATT (8.9 mm) and in our leanest subject (ATT = 1.4 mm). The model does not take into account the different light-scattering properties of fat and muscle. The light travels in a 'banana shape' form from source to detector [Cui et al. 1991], and the maximum penetration depth is roughly half the interoptode distance. Approximately 49% of the measurement depth (17.5 mm) in our subject with the largest ATT comprises muscle tissue, while this value was 92% for our leanest subject.
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ATT (+ skin)
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ATT (+ skin)
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ATT = 1.4 mm
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Fig. 4 Combined data supporting the confounding effect of ATT on NIRS 2OVm �
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Yamamoto et al. 1999 (*), and Niwayama et al. 1998 (Å). All data are presented in units
of mlO2⋅min-1⋅100g-1, except the data from Yamamoto et al. 1999, which are presented in
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SUMMARY
Near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (31P-MRS) have been used in this study as complementary methods for the investigation of in vivo skeletal muscle metabolism, measured simultaneously and within the same volume of interest. In order to investigate the differences and similarities between both techniques, we studied muscle function in normal controls and a group of Friedreich ataxia (FRDA) patients in which mitochondrial function is thought to be impaired. Eleven healthy subjects and fifteen FRDA patients were tested during 2 phases of 3 min aerobic and ischemic isometric exercise and subsequent recovery. Immediately after the start of both exercise phases, a rapid deoxygenation and depletion of phosphocreatine (PCr) was found, accompanied by a moderate increase in the intracellular pH (pHi). Subsequently, pHi decreased indicating lactic acid formation during anaerobic glycolysis, while the rate of deoxygenation and PCr depletion slowed down. The results show that oxidative phosphorylation during exercise was present, even during ischemia when O2 stores were thought to be depleted. Similar responses in NIRS and 31P-MRS were found for FRDA patients and controls. Although PCr recovery after cessation of exercise was significantly delayed in FRDA, NIRS showed no indication for an impaired oxygen consumption. Our data are suggestive for either partial uncoupling of the electron-transport chain or reduced ATP synthesis at the level of complex V (ATPsynthase), the adenine nucleotide translocator (ANT), or mitochondrial creatine kinase. The results of this study demonstrated the additional value of NIRS in the complementary use with 31P-MRS for the investigation of in vivo muscle metabolism enabling both oxidative and anaerobic processes to be measured noninvasively and simultaneously within the same muscle area.
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INTRODUCTION
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Fig. 1. Individual, simultaneously measured signals for near-infrared spectroscopy (NIRS) and phosphorus magnetic resonance spectroscopy (31P-MRS) during aerobic and ischemic exercise and its recovery in a healthy volunteer. A) NIRS. Oxyhemoglobin (O2Hb), deoxyhaemoglobin (HHb), and total haemoglobin (tHb) signals measured at 20 Hz and displayed real-time on screen. B) 31P-MRS. Simultaneously measured phosphocreatine (PCr) tracing at 0.1 Hz. The grey bar represents the periods of sustained isometric exercise at 30% of the individual maximum voluntary contraction force (MVC). The black bar represents the period of arterial occlusion.
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Fig. 3. Mean (±SD) values for NIRS and 31P-MRS tracings in Friedreich ataxia (FRDA) patients and healthy controls. A) O2Hb signals, B) PCr signals, and C) intracellular pH (pHi). The grey bar represents the periods of sustained isometric exercise at 30% MVC. The black bar represents the period of arterial occlusion.
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Table 1. Mean (± SD) values for phosphorus magnetic resonance spectroscopy (31P-MRS) and near-infrared spectroscopy (NIRS) variables in Friedreich ataxia (FRDA) and healthy controls.
Healthy subjects (11) FRDA patients (15)
Mean ± SD Range Mean ± SD Range P-value
Initial values
Pre-exercise intracellular pH 7.02 ± 0.03 6.96-7.11 7.01 ± 0.03 6.96-7.06 0.44
End-occlusion O2Hb deoxygenation (µM) -17.9 ± 4.9 -23.9 - -7.5 -15.7 ± 9.3 -38.0 - -5.9 0.45
2OVm � during AO (mlO2⋅min-1⋅100g-1) 0.05 ± 0.02
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0.02-0.07 0.05 ± 0.04
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0.01-0.14 0.85
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2OVm � (mlO2⋅min-1⋅100g-1) 0.26 ± 0.18
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0.10-0.57 0.27 ± 0.33
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0.03-1.04 0.92
End-exercise O2Hb deoxygenation (µM) -25.1 ± 13.3 -46.8-3.3 -20.7 ± 14.1 -51.9-1.3 0.44
End-exercise [PCr] (%[PCr]) 75.8 ± 10.7 59.6-90.4 74.4 ± 14.7 45.3-92.6 0.78
End-exercise pH 6.98 ± 0.09 6.77-7.08 6.97 ± 0.05 6.86-7.05 0.90
τ-value of O2Hb recovery (s) 29.9 ± 23.2 6.1-73.5 22.7 ± 5.8 13.9-33.1 0.36
τ-value of PCr recovery (s) 52.6 + 22.5 19.5-94.3 82.6 + 40.8 39.8-178.6 0.04
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2OVm � (mlO2⋅min-1⋅100g-1) 0.16 ± 0.09
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End-exercise O2Hb deoxygenation (µM) -37.4 ± 9.6 -59.5-15.4 -32.5 ± 18.6 -64.6-8.5 0.44
End-exercise [PCr] (%[PCr]) 61.0 ± 15.7 29.7-79.7 66.3 ± 18.7 20.3-98.0 0.45
End-exercise pH 6.94 ± 0.08 6.77-7.00 6.93 ± 0.06 6.79-7.01 0.90
τ-value of O2Hb recovery (s) 41.7 ± 28.2 17.2-116.3 30.6 ± 13.3 10.1-52.1 0.25
τ-value of PCr recovery (s) 57.1 ± 25.2 26.0-105.3 86.3 ± 28.6 46.7-161.3 0.01
2OVm � = muscle oxygen consumption, AO = arterial occlusion, O2Hb = oxyhaemoglobin, PCr =
phosphocreatine, (n) = number of subjects included in calculation. P ≤ 0.05 is considered statistically significant.
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Fig. 4. Strongly simplified scheme of the pathway of oxidative phosphorylation (OXPHOS) from blood born substrates to adenosine triphosphate (ATP) with a final role for oxygen at complex IV. The respiratory chain is presented by the roman-numbered squares, existing of five complexes. Electrons (e-) are transported from complex I to complex IV where they are adopted by O2 to form H2O. ATP then, is formed from adenosine diphosphate (ADP) by complex V, (ATPsynthase). Subsequently, phosphocreatine (PCr) can be resynthesised from creatine (Cr) by the adenine nucleotide translocator (ANT) and mitochondrial creatine kinase (CKm). MO; mitochondrial outer membrane, MI; mitochondrial inner membrane.
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Glycolysis overall:
glucose + 2NAD + 2ADP + 2Pi → 2pyruvate + 2ATP + 2NADH
Glycolysis, citric acid cycle, and respiratory chain overall:
glucose +6O2 + 36Pi + 36ADP → 6CO2 + 36ATP + 42H2O
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Introduction Methods Subject population Quantitative NIRS measurements
Oxygen consumption Blood flow Venous oxygen saturation Half-recovery time Reoxygenation rate
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QUANTITATIVE NIRS VARIABLES
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INTRODUCTION
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METHODS
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Fig. 1 Distribution and mean (±SD) values for the physical characteristics of the 139 healthy volunteers. Distribution is plotted as bars, mean as straight lines, and standard deviation as dotted lines. The median, instead of mean, is shown when distribution failed normality. Male (black bars) and female (white bars) subjects are presented separately. A) Distribution of age with median. B) Distribution of height with mean ± SD. C)
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Fig. 2 Real-time NIRS tracings of oxyhaemoglobin (O2Hb), deoxyhaemoglobin (HHb), and total haemoglobin (tHb) in response to 20 s of venous occlusion (VO) and 45 s of arterial occlusion (AO). Note that recovery after VO is very rapid while recovery from AO takes more than two minutes.
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QUANTITATIVE NIRS VARIABLES
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Table 1. Quantitative NIRS variables in healthy subjects at rest
NIRS variable Normality Mean ± SD Median n P25 P75
Venous occlusion
Forearm blood flow (ml⋅min-1⋅100ml-1) No - 0.88 104 0.63 1.35
Venous saturation (%) Yes 59 ± 20 - 23 46 72
Oxygen consumption (mlO2⋅min-1⋅100g-1) Yes 0.12 ± 0.06 - 24 0.08 0.15
Arterial occlusion
Oxygen consumption (mlO2⋅min-1⋅100g-1) Yes 0.11 ± 0.04 - 138 0.08 0.14
Reoxygenation rate (µM⋅s-1) Yes 2.0 ± 1.0 - 33 1.3 2.8
Half-recovery time O2Hb (s) No - 3.8 33 3.4 4.8
Half-recovery time HHb (s) No - 6.7 34 5.5 7.9
Half-recovery time tHb (s) Yes 1.4 ± 0.8 - 29 1.0 1.8
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Table 2. Within-subject variability of in vivo quantitative NIRS variables in healthy subjects at rest
NIRS variable CV (%) nCV
Venous occlusion
Forearm blood flow (ml⋅min-1⋅100ml-1) 25.2 103
Venous saturation (%) 37.7 21
Oxygen consumption (mlO2⋅min-1⋅100g-1) 33.5 104
Arterial occlusion
Oxygen consumption (mlO2⋅min-1⋅100g-1) 16.3 83
Reoxygenation rate (µM⋅s-1) 23.4 6
Half-recovery time O2Hb (s) 16.9 6
Half-recovery time HHb (s) 16.1 6
Half-recovery time tHb (s) 53.9 6
CV: coefficient of variation, indicating the within-subject variability derived from repeated measurements. nCV: number of subjects in calculation of CV.
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Table 3. Resting quantitative NIRS muscle oxygen consumption (in mlO2⋅min-1⋅100g-1) from literature.
Authors DPF IO Method Analysis Muscle n Mean ± SD
Van Beekvelt et al. 2002b 4.0 35 AO O2Hb FDS 6 0.14 ± 0.02
4.0 35 AO Hbdiff FDS 6 0.15 ± 0.03
Van Beekvelt et al. 2001a 4.0 35 AO Hbdiff FDS 78 0.11 ± 0.04
Van Beekvelt et al. 2001b 4.0 35 AO Hbdiff FDS 26 0.11 ± 0.03
4.0 50 AO Hbdiff FDS 26 0.09 ± 0.03
4.0 35 AO Hbdiff BR 26 0.13 ± 0.03
4.0 50 VO HHb FDS 26 0.08 ± 0.04
4.0 35 VO HHb BR 26 0.14 ± 0.10
Kragelj et al. 2000* ? 40 AO O2Hb Foot 6 0.08 ± 0.01
Van Beekvelt et al. 1999 4.0 35 AO O2Hb FDS 27 0.11 ± 0.03
Paunescu et al. 1999 ? 20-35 VO HHb GASTR 8 0.10
Niwayama et al. 1999 ? 30 AO O2Hb Forearm 15 0.12 ± 0.05
? 30 AO O2Hb Forearm 15 0.21 ± 0.03
Binzoni et al. 1998* 5.0 30 AO O2Hb GASTR 8 0.08 ± 0.05
5.0 30 AO O2Hb GASTR 8 0.16
5.0 30 AO O2Hb GASTR 8 0.04
De Blasi et al. 1997* 4.16 35 VO Hbdiff BR 10 0.07 ± 0.02
4.16 35 AO Hbdiff BR 10 0.06 ± 0.02
Colier et al. 1995* 4.3 45 AO O2Hb SOL 11 0.06 ± 0.03
De Blasi et al. 1994* 4.3 30-40 VO HHb BR 11 0.10 ± 0.03
De Blasi et al. 1993* 3.1-5.1 28-32 AO Hbdiff BR day 1 7 0.03 ± 0.01
3.1-5.1 28-32 AO Hbdiff BR day 2 0.05 ± 0.02
De Blasi et al. 1992* 3.59 30-35 AO Hbdiff BR 6 0.11 ± 0.06
Cheatle et al. 1991 5.4 30-50 AO O2Hb Calf 21 0.20
DPF: differential path-length factor, IO: interoptode distance in mm, AO: arterial occlusion, VO: venous occlusion, FDS: flexor digitorum superficialis muscle, BR: brachioradialis muscle, GASTR: gastrocnemius muscle, SOL: soleus muscle, n: number of subjects, ?: no data available. Values from studies marked with * are converted to mlO2⋅min-1⋅100g-1.
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Table 4. Forearm oxygen consumption measured by other methods.
Authors Method Flow measurement Localisation n Mean ± SD
Van Beekvelt et al. 2001b Fick Plethysmography Forearm 26 0.15 ± 0.06
Sako et al. 2001* 31P-MRS - FDS 12 0.16 ± 0.02
Hamaoka et al. 1996* 31P-MRS - FDS 5 0.16
Wang et al. 1990* 31P-MRS - Forearm 1 0.17
Hartling et al. 1989* Fick Dye dilution Forearm 5 0.14 ± 0.09
Wahren 1966 Fick Plethysmography Forearm 10 0.30 ± 0.09
Andres et al. 1956 Fick Dye dilution Forearm 8 0.26 ± 0.08
Mottram 1955 Fick Plethysmography Forearm 16 0.23 ± 0.07
Holling 1939* Fick Plethysmography Forearm 34 0.11
Mean (± SD) forearm oxygen consumption in mlO2⋅min-1⋅100g-1. Fick oxygen consumption is derived from the arteriovenous O2 difference (derived by blood gas analysis) times blood flow. 31P-MRS: phosphorus magnetic resonance spectroscopy, FDS: flexor digitorum superficialis muscle, n: number of subjects. Values from studies marked with * are converted to mlO2⋅min-1⋅100g-1.
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Table 5. Resting quantitative NIRS blood flow values (in ml⋅min-1⋅100ml-1) from literature.
Authors DPF IO Muscle n Mean ± SD
Van Beekvelt et al. 2001a 4.0 35 FDS 78 1.28 ± 0.82
Van Beekvelt et al. 2001b 4.0 35 FDS 26 0.72 ± 0.32
4.0 50 FDS 26 0.57 ± 0.26
4.0 35 BR 26 1.42 ± 1.04
Van Beekvelt et al. 1999 4.0 35 FDS 27 0.72 ± 0.33
Paunescu et al. 1999 ? 20-35 GASTR 8 0.73
De Blasi et al. 1994 4.3 30-40 BR 11 1.9 ± 0.8
Edwards et al. 1993 # $ 3.59 Through Forearm 6 2.35 ± 1.11
DPF: differential path-length factor, IO: interoptode distance in mm, FDS: flexor digitorum superficialis muscle, BR: brachioradialis muscle, GASTR: gastrocnemius muscle, n: number of subjects, ?: no data available. # Blood flow measured by intravenous tracer instead of venous occlusion method. $ light detection through the arm instead of parallel optode placement.
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Table 6. Forearm blood flow measured by other methods.
Authors Method Localisation n Mean ± SD
Van Beekvelt et al. 2001b Plethysmography Forearm 26 2.1 ± 0.7
De Blasi et al. 1994 Plethysmography Forearm 11 3.4 ± 1.3
Edwards et al. 1993* Plethysmography Forearm 7 2.2 ± 1.1
Hartling et al. 1989 Dye dilution Forearm 5 3.6 ± 2.2
Wahren 1966 Plethysmography Forearm 10 3.8 ± 1.1
Andres et al. 1956 Dye dilution Forearm 14 3.6
Mottram 1955 Plethysmography Total forearm 16 3.2
Estimation Forearm muscle 16 2.9
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Table 7. Resting quantitative NIRS venous oxygen saturation (in %) from literature.
NIRS Co-oximeter
Authors n Localisation Median Range Median Range
Yoxall et al. 1997 19 adults Forearm 71.3 50.1 – 80.0 71.9 50.4 – 92.0
Yoxall et al. 1996 16 infants Forearm 71.6 50.7 – 79.7 75.9 60.8 – 90.7
n: number of subjects.
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Fig. 5 Venous oxygen saturation (SvO2) in the flexor digitorum superficialis muscle, A) calculated during venous occlusion. B) distribution of individual values. Mean is presented as a straight line, SD as dotted lines.
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Fig. 6 Half-time recovery, calculated as A) the time needed for half recovery of O2Hb from maximum deoxygenation at the end of arterial occlusion or exercise to maximum re-oxygenation during hyperaemia, and B) the tau value derived from a mono-exponential curve-fit of O2Hb recovery after exercise as is standard for calculation of PCr resynthesis with 31P-MRS.
�Table 8. Half-recovery time (s) after exercise from literature.
Authors Exercise protocol Muscle n Mean ± SD
McCully et al. 1994a Submax PF, incremental, 5 min GASTR 5 28 ± 6
Max PF, 64 s GASTR 5 29 ± 6
McCully et al. 1994b PF, 3.4-9.1 kg, 1 min GASTR 6 22 ± 9
Chance et al. 1992 100% MVC QUADRI 7 36 ± 4
n: number of subjects, PF: plantar flexion, GASTR: gastrocnemius muscle, QUADRI: quadriceps muscle.
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Fig. 8 Rate of reoxygenation (∆O2Hb) in the flexor digitorum superficialis muscle, calculated immediately after cessation of arterial occlusion at rest. A) Concentration changes of oxyhaemoglobin (O2Hb). B) Distribution, mean (straight line), and SD (dotted lines) for the individual values.
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CLINICAL APPLICATIONS
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�Table 1. Near-infrared spectroscopy in metabolic/mitochondrial myopathies.
Authors n Patients
Bank et al. 1994 1 Cytochrome c oxidase deficiency
3 Myophosphorylase deficiency (McArdle)
3 Phosphofructokinase deficiency
2 Carnitine palmitoyl transferase deficiency
Bank et al. 1995 2 Cytochrome c oxidase deficiency
3 Myophosphorylase deficiency (McArdle)
3 Phosphofructokinase deficiency
Abe et al. 1997 3 Chronic progressive external ophthalmoplegia (CPEO)
1 Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like
episodes (MELAS)
Gellerich et al. 1998 1 Exercise induced myalgia
1 Proximal weakness + pseudohypertrophy
1 External ophthalmoplegia
Wariar et al. 2000 1 Coenzyme Q10 deficiency
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MITOCHONDRIAL MYOPATHIES
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Fig. 1. Strongly simplified scheme of the pathway of oxidative phosphorylation (OXPHOS) from blood born substrates to adenosine triphosphate (ATP). The respiratory chain is presented by the roman-numbered squares, existing of five complexes. Electrons are transported from complex I to complex IV where they are adopted by O2 to form H2O. ATP then, is formed from adenosine diphosphate (ADP) by complex V, (ATPsynthase). Subsequently, phosphocreatine (PCr) can be resynthesised from creatine (Cr) by the adenine nucleotide translocator (ANT) and mitochondrial creatine kinase (CKm). MO; mitochondrial outer membrane, MI; mitochondrial inner membrane.
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CHAPTER 7
� 122
Neuromuscular disorders
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Chronic Progressive External Ophthalmoplegia (CPEO):
CPEO is the most frequent form of adult mitochondrial myopathies. Ptosis and external
ophthalmoplegia are usually the first clinical signs because mitochondrial volume of the extraocular
muscles is several times greater than that of other skeletal muscle. Bindoff et al. 1997: in addition to
ophthalmoplegia, most patients have mild proximal myopathy. Patients might have pigmentary
retinopathy, ataxia, sensory neural deafness, mild pyramidal or extrapyramidal features. The onset
might be as late as the fifth or sixth decade. Muscle biopsy shows cytochrome oxidase (COX)
negative fibres and ragged red fibres (RRF). Mitochondrial DNA (mtDNA) analysis will show a single
large scale rearrangement in approximately 50% (sporadic cases). In a significant proportion of the
other patients, point mutations of mtDNA can be defined.
Dermatomyositis:
Dermatomyositis is an inflammatory muscle disease with the identifying clinical features of erythema
of the skin in combination with muscle weakness and pain (Engel et al. 1990). It is a multisystem
disorder that can occur at any age from infancy to late adult onset. Apart from skin and muscle,
dermatomyositis is associated with many other organs and systems (e.g. heart and lungs) as well as
with malignancy (Hill et al. 2001). The cause of dermatomyositis is still unknown, but a strong
indication for autoimmune mechanisms exists (Dalakas 1998). Dermatomyositis is characterised by
complement mediated capillary necrosis, resulting in ischemia and hypoperfusion. The pathological
features consist of a decreased number of capillaries per muscle fibre and necrosis of single muscle
fibres or clusters of fibres at the periphery of the fasciculi (Engel et al. 1990). Although the mechanism
is not completely understood, it is thought that the muscle fibre injury could be secondary to ischemia
caused by the decrease in capillary density. Muscle fibre regeneration and an increased number of
capillaries were shown after intravenous immune globulin treatment (Dalakas et al. 1993), but
corticosteroids are still considered to be the first line of therapy.
Friedreich ataxia:
Friedreich ataxia (FRDA) is a progressive degeneration of the dorsal root ganglia, spinocerebellar
tracts, corticospinal tracts and Purkinje cells of the cerebellum. It is characterised by a gradual loss of
coordination, usually the earliest and most prominent characteristic of the disease. Increasing
impairment of balance and movement eventually lead to the loss of the ability to walk. It is also
associated with cardiomyopathy. Friedreich Ataxia is an autosomal recessive neurodegenerative
disorder characterised by an expanded (GAA)n trinucleotide repeat in intron 1 of the frataxin gene on
chromosome 9q13 (Campuzano et al. 1996). It is the most common hereditary ataxia occurring with a
frequency of 1 in 50 000 in the Caucasian population. Frataxin is associated with the inner membrane
of the mitochondria, and mutations in the frataxin gene are thought to lead to impaired mitochondrial
function. The actual function of Frataxin remains to be elucidated.
CLINICAL APPLICATIONS
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SUMMARY
Five patients with chronic progressive external ophthalmoplegia (CPEO) and 27 healthy controls were examined by near-infrared spectroscopy (NIRS) for the noninvasive and direct quantitative measurement of muscle oxygen consumption and forearm blood flow. NIRS measurements were obtained at rest and during static isometric handgrip exercise at 10% of the maximum voluntary contraction (MVC) force. A significantly decreased oxygen consumption at rest as well as during exercise was found in patients with CPEO. Our results suggest that NIRS is able to discriminate between CPEO patients and healthy controls, which makes NIRS a valuable tool in the diagnostic workup of patients suspected to have a mitochondrial myopathy.
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NIRS IN CPEO
� 127
INTRODUCTION
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CHAPTER 8
� 128
�Table. Clinical characteristics of patients with sporadic chronic progressive external ophthalmoplegia
No Sex/age
(yr)
MVC
(N)
Disease
duration
(yr)
Fatiguea Prox. Muscle
Strength
(MRC)
Modified
Rankin
scaleb
Muscle
Biopsy
RRFc
Serum
lactated
(µmol/L)
1 M/54 132 28 - 4/5 2 + 1520
2 M/19 262 3 + 5/5 2 ++ 1586
3 F/36 168 4 - 5/5 2 ++ 1288
4 F/42 153 22 +++ 3/5 3 ++ 844
5 F/54 100 27 ++ 3/5 3 + 2660
a : - = not present; + = mild; ++ = moderate; +++ = severe b : Modified Rankin scale described by Swieten et al. [van Swieten et al. 1988] c : RRF = ragged red fibres; + = present; ++ = abundant d : Normal values: < 1700 µmol/L M = male; F = female; MVC = maximal voluntary contraction force; MRC = medical research council �
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Fig. 1. Representative raw NIRS data as displayed real time on screen. Oxyhemoglobin (O2Hb), deoxyhaemoglobin (HHb), and the sum of O2Hb and HHb, reflecting total haemoglobin (tHb), are shown during A) arterial occlusion (240 mmHg) and B) venous occlusion (50 mmHg). Oxygen consumption is calculated during arterial occlusion as the rate of decrease in O2Hb indicated by the straight line in Fig. A. Forearm blood flow is calculated during venous occlusion as the rate of increase in tHb indicated by the straight line in Fig. B.
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Fig. 2. Near infrared spectroscopy values for muscle oxygen consumption ( 2OVm � ) and
forearm blood flow (FBF) in patients with chronic progressive external ophthalmoplegia (CPEO) and healthy control subjects A) at rest and B) during static isometric handgrip exercise at 10% of the subject’s maximum voluntary contraction force (MVC). Individual
values of 2OVm � and FBF are shown for the patients with CPEO. Mean ± SD in both
directions are shown for the control group.
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DISCUSSION
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POSTSCRIPTUM:
NEAR-INFRARED SPECTROSCOPY IN CPEO: ADIPOSE TISSUE
THICKNESS CONFOUNDS DECREASED MUSCLE OXYGEN CONSUMPTION
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SUMMARY
Near-infrared spectroscopy (NIRS) is a direct, noninvasive optical method for the measurement of local oxygenation and haemodynamics in muscle tissue. Although it has recently been used for diagnosis of metabolic myopathies, it has until now never been used in inflammatory myopathies. Because dermatomyositis is a muscle disorder characterised by complement mediated capillary necrosis, resulting in ischemia and hypoperfusion, we have used NIRS to study the effect of corticosteroid treatment in dermatomyositis. Clinical improvement correlated with NIRS, showing an increase in local muscle oxygen consumption and reoxygenation rate, indicating normalisation of microvascular function. This study shows that NIRS is able to detect therapy effect; direct, noninvasively, and with relative ease.
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NIRS IN DERMATOMYOSITIS
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Fig. 1 NIRS oxyhaemoglobin (O2Hb) and deoxyhaemoglobin (HHb) signal during exercise
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linear increase in HHb during arterial occlusion. Reoxygenation rate (∆O2Hb) is determined as the rate of increase in O2Hb over the initial 3 s after cessation of arterial occlusion.
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OUTLINE
Thesis objectives Methodological considerations
Nature of signal Path-length factor Haemoglobin vs. myoglobin Skinfold thickness Venous vs. arterial occlusion method Increase tHb during arterial occlusion
Clinical considerations Sensitivity/specificity Quantitative measurement Clinical applicability
Future perspectives Bio-energetic characterisation Effect of therapy Multi-channel NIRS Pathophysiology of myopathies
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THESIS OBJECTIVES
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This thesis is financially supported by:
Biomedical Engineering Department University Medical Centre Nijmegen.
The Biomedical Engineering Department specifies, designs and builds dedicated measurement devices for medical scientific research and is specialized in transforming research questions into technical solutions. The Oxymon system is an example of one of our sophisticated projects. Oxymon has enabled many scientists to perform leading research in the area of Near Infra Red Spectroscopy.
Characteristics The Biomedical Engineering Department is ISO 9001 certified and combines employees with different technical specialisms:
• Electronics
• Data acquisition software
• (fine) Mechanics
• Optics In case specific capacities are required we fall back on our network of sub-suppliers.
For any further information please contact: Biomedical Engineering Department tel: +31 (0)24 3614860 UMCN 171 Instrumentele Dienst fax: +31 (0) 24 354 1211 POBOX 9101 6500 HB Nijmegen E-mail: [email protected] The Netherlands Web-site: http://www.kun.nl/id
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