Within subject and between subject variation in skull thickness

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Tae Sun Yoo
Department of Medical Biophysics
University of Western Ontario
Supervisor: Dr. Keith St Lawrence and Ph.D.
candidate Jonathan Elliott
Near Infrared Spectroscopy &
Principles • Near infrared spectroscopy is a
powerful optical technique used to
measure cerebral blood flow (CBF)
and cerebral blood oxygenation.
Blood Flow Technique:
1) Bolus injection light-absorbing dye,
indocyanine green (ICG)
2) Monitor passage of ICG through
brain by NIRS
3) CBF determined by shape of timeconcentration data
Clinical Relevance of NIRS
 Brain injury is a leading cause of deaths and disability in
Canada.
 NIRS can be used to assess brain health at the bedside of
head-trauma patients
 NIRS works well with infants, but not with adults
 Problem is signal contamination from extracerebral layer
 Consequence is reduced sensitivity to brain leading to
underestimation of CBF.
Approach
 MRIcro was used to import MRI images and Image
J was used to obtain length of extracerebral layer
(ECL) thickness values across the circumference of
the head (from 0 to 360˚)
Hypothesis
 Variations in ECL thickness across the subject will be
sufficient to affect the NIRS brain attenuation signal to
measure accurate cerebral blood flow (CBF).
Method
 Brain MRI images were acquired from five young
healthy subjects & viewed by MRIcro.
 Anterior Commissure (AC) was chosen as the
reference location for all subjects
 MRI images were exported in 2 transverse slices
per subject.
Method
 Brain MRI images were loaded onto “ImageJ”.
 By using a line tool and fill function, outlines were
drawn from 0 to 360˚ within the image.
 Color picker function was used with pencil tool.
land markers were made at two locations.
 Total (ECL) thickness measurements were done by
moving a line tool at 10˚increment with use of
measurement function.
90˚
Angle (θ)
Position
180˚
0, 360˚
270˚
Note: MR images were calibrated by 1 x 1 mm
Angle (θ) from 0° to 360°
Record: Total ECL
thickness made by Δ10°
increment
ECL thickness
Scalp
Skull
Results
20
Mean ECL thickness of subjects (1-5)
at [AC] based on region
20
Mean ECL thickness of subjects (1-5)
at [AC+20mm] based on region
15.7 ± 3.83
14.9 ± 3.88
15
14.2 ± 2.12
10
5
13.6 ± 2.33
Mean ECL thickness (mm)
Mean ECL thickness (mm)
15.2 ± 4.58
14.9 ± 2.18
13.2 ± 2.45
15
10.9 ± 2.10
10
5
0
0
Region I: Region II: Region III: Region IV:
320-40 ˚
50-130˚
140-220˚
230-310˚
Region I: Region II: Region III: Region IV:
320-40 ˚
50-130˚
140-220˚
230-310˚
Mean ECL thickness from Sub 1-5 at AC vs AC+20mm
18
15.1 ± 1.30
Mean ECL thickness (mm)
16
13.1±1.66
14
*p < 0.05
12
10
8
6
4
2
n = 37
0
AC
∆ in ECL thickness between AC & AC +20mm:
 ECL thickness was slightly thinner at AC
above 20mm!
AC+20mm
Brain contribution to total
pathlength
100%
Effect of ECL thickness on
% brain signal
80%
60%
Mean, AC+20, Region I
35%
40%
Subject 3, AC, Region I
9%
20%
0%
2
4
6
8
10
12
14
16
18
ECL thickness (mm)
20
As ECL thickness increased, % of brain signal is reduced
22
24
26
0.1
ICG concentration (uM)
0.08
Pure brain curve
0.06
0.04
0.02
0
-0.02
Pure scalp curve
0
10
20
30
Time (s)
0.04
0.025
0.02
0.015
0.01
0.005
0
0
10
20
30
40
Time (s)
Mean, AC+20, Region I
Brain contribution: 35%
50
60
ICG concentration (uM)
ICG concentration (uM)
0.03
50
60
-3
14
0.035
-0.005
40
x 10
12
10
8
6
4
2
0
-2
0
10
20
30
Time (s)
40
Subject 3, AC, Region I
Brain contribution: 9%
50
60
Discussion
Main limitations: There isn’t a decent imaging tool
which resolves different ECL layers separately.
 Source of errors:
. Small sample size (5 subjects)
. Resolution of MR image quality
(reduced with “zoom in” function)
Discussion
Future works on identifying ECL thickness variability:
 By standardizing variation of ECL thickness, more
precise and reliable CBF measurements can be made
on adults.
 In near future, individualized approach on making an
adjustment on CBF measurements are possible by
removing ECL (skull and scalp) contamination.
Conclusion
 Mean ECL thickness across the circumference from subject
1 to 5 at AC+20mm was thinner by 2mm than at AC.
 Based on regions (I-IV), forehead region I at AC above
20mm was shown to be the thinnest mean ECL thickness.
 Thus, thinner the ECL thickness, better the CBF
measurements by increased in contribution of brain signal
(more light propagates into brain and reduced ECL
contamination).
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