Académique Documents
Professionnel Documents
Culture Documents
TITLE PAGE
Theoretical Modelling of Alveolar Resonance Mechanism of Ultrasound-Induced Lung
Haemorrhage
D. John Jabaraja
Dept. of Medical Physics, Faculty of Physical Sciences,
Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
Acknowledgements
This work was supported in part by the USM PGRS Grant and the UniKL Financial
Assistance Scheme. D. John Jabaraj thanks his wife, K. Suganthi Maria, for her unfathomable
love and encouragements along the arduous path of seeking knowledge.
Corresponding author
D. John Jabaraja
Add: Dept. of Medical Physics, Faculty of Physical Sciences,
Universiti Sains Malaysia, 11800 USM, Penang, Malaysia.
Tel: 60174194717
E.mail: jojab77@yahoo.com
2
Abstract
The possibility of the ultrasound-induced lung haemorrhage occurring in adult human during
diagnostic ultrasound examination is studied here. This study is based on the hypothetical
alveolar resonance mechanism of the ultrasound-induced lung haemorrhage. The alveolar wall
is initially modelled here as a square membrane with fixed-boundary, and then theoretically
subjected to vibration analysis. The equation of threshold pressure for the occurrence of
ultrasound-induced lung haemorrhage is derived. A comparison test against past experimental
data validates the use of the square membrane model of the alveolar wall in studying the
ultrasound induced lung haemorrhage. This study predicts that the ultrasound-induced lung
haemorrhage in adult human can be prevented if the ultrasound frequency is kept above 1.69
MHz while the Mechanical Index do not exceed 1.9.
Keywords
Ultrasound-induced lung haemorrhage; alveolar resonance mechanism; resonant frequency;
threshold pressure; theoretical modelling.
MANUSCRIPT TEXT
Introduction
The Ultrasound-Induced Lung Haemorrhage
The ultrasound (US) at diagnostic exposure level is detrimental as it is shown to cause lung
haemorrhage in mice, rats, rabbits, monkeys and pigs [1, 2]. Nevertheless, there is no
evidence of the US-induced lung haemorrhage occurring in human, possibly due to the lack of
experimental studies. Only a single study reports that US-induced lung haemorrhage do not
occur in humans at 3.5 MHz minimum frequency at 2.4 MPa maximum pressure [3].
The mechanism of alveolar resonance, for producing US-induced lung haemorrhage, have not
been explored experimentally or theoretically [9]. A thorough survey of literature gave no
indication that the alveolar resonance mechanism hypothesis has been tested or studied.
Belete [11] states that cell wounding in parenchyma tissue occurs significantly at linear strain
of 0.08. The linear strain forms fractures in the plasma membrane of the alveolar epithelial
cells [12]. This linear strain of 0.08, that damages elements within the alveolar wall and cause
haemorrhage, will be called here as the yield linear strain.
Methods
The Modelling of the Alveolar Wall Structure
The defining structure of the alveolus is its wall. Several assumptions were made concerning
the alveolar wall and its behaviour for the purpose of modelling.
The alveolar wall contains elastin fibres and plasma membrane (with lipid bi-layers) [13]. If
the deformation of the alveolar wall is reversible and small, then it obeys the Hookes Law
[14]. Thus, the alveolar wall is assumed to be isotropic and linearly elastic. The linear theory
of vibration is assumed to be applicable to the alveolar wall.
The alveolar wall is further assumed as a square membrane with fixed boundary. The facets of
the alveolar wall are in reality shaped as flat irregular pentagon [15]. However, for
simplification purposes, the shape of the alveolar wall facet is modelled here as a square. The
alveolar wall is modelled as flat membrane instead as plates because its stiffness is small [16].
The alveolar wall is shared among alveoli. This provides radial support to the alveolar wall
facet at its edges [17].
ny
= c T L-1 ( n x 2 + n y 2 )
(1)
The resonant frequency mode is denoted as nx, ny and L is the radius while cT is the transverse
wave velocity on alveolar wall.
If the membrane model of the alveolar wall is forced to vibrate at fundamental mode by the
external US waves, then the resonant amplitude is [20];
Z max =
F0
Q
o m eq
(2)
with F0 as rarefaction peak force of US waves. The angular fundamental frequency of the
membrane model is denoted as o while its equivalent mass is meq. The equivalent mass
6
depends on the shape of the membrane vibration at fundamental mode. The quality (Q) factor
of the vibrating system is denoted as Q.
As the US wavelength is larger than the dimension of alveolar wall surface area, it can be
assumed that the force imparted on the surface by the US wave is uniformly distributed. Thus,
the peak rarefaction pressure (Po) of US waves applied to a membrane surface area (A) is
related to the peak rarefaction force (Fo) by; P o = F o / A .
P0
o eq
2
(3)
(4)
The Q-factor
The Q-factor of membrane is approximated to be due to membranes support loss only [21].
Hence the Q-factor of vibrating square membrane at fundamental mode is (Appendix A),
Q = Q support = 0 . 34 ( L / d )
(5)
(6)
Therefore, the equivalent area density at fundamental mode for the vibrating square
membrane is,
eq = 0 . 40 d
(7)
Where the density is denoted as while d is thickness and A is the surface area
= ( A1 A 0 ) / A 0
(8)
The initial area is denoted as A0 while A1 is the deformed area. The square membranes shape
while at rest is a flat square. Thus, the initial area is,
A 0 = L2
(9)
The membranes shape at fundamental mode is a square based dome (Fig. 1) [18]. If the
height (Z) is smaller than the dimension of the membrane, then the shape can be simplified
into a square based pyramid, as an approximation (Fig. 1). Thus, the deformed area is;
A1 = 2 Lp
(10)
(11)
The areal strain at resonance (r) for deformed square membrane due to resonant amplitude
(Zmax) in the fundamental vibration mode is analyzed by applying E.9-11 into E.8.
= ( A1 A 0 ) / A 0
r =
( 2 L [( Z max ) 2 + ( L / 2 ) 2 ] ) ( L2 )
( L2 )
(12)
Results
Fundamental Frequency
The fundamental frequency of the square membrane model occurs when mode is nx = ny = 1.
The transverse wave velocity on alveolar wall is determined to range from 0 489 m/s [23].
The diameters of the alveolus for the adult mouse and human are 40 80 m and 200 400
m respectively [24]. By utilizing E.1, the fundamental frequencies of the square membrane
model of alveolar wall for adult mouse is calculated to be 0 8.64 MHz while for the adult
human is 0 1.73 MHz.
The threshold pressure equation for producing damage in the square membrane model of the
alveolar wall is derived by substituting E.5, 7 & 12 into E.3;
Z max =
P0
o eq
2
P 0 = o 2 eq Q 1 Z max
= ( 2 f 1,1 ) 2 ( 0 .40 d )( 0 . 34 L / d ) 1 ( L [ r 2 + 2 r ] )
P 0 = 23 . 223 f 1,1 2 d 2 [ r 2 + 2 r ]
(13)
Observe that the linear fundamental frequency (f1,1) of the square membrane model is related
to the angular fundamental frequency by, o = 2 f 1,1 .
9
The threshold pressure equation should be concerning the minimum pressure for inducing
damage. Hence, the minimum density value of the alveolar wall (soft tissue) of 1026 kg / m3
[25] is applied into E.13. Furthermore, the minimum areal strain of resonance of 0.0639
(Appendix B) is also substituted in E.13. Thus E.13 is reduced to;
P 0 = 0 . 00865 f 1,1 2 d 2
MPa
(14)
The threshold pressure formulas for specific mammals are obtained by inserting the minimum
alveolar wall thickness values into E.14.
The MI Index
The mechanical index, MI = 1.9 is plotted in the threshold pressure vs. fundamental frequency
graph for the square membrane model of human alveolar wall, in order to analyze the MI
relation with the US-induced lung haemorrhage for human (Fig. 3). The minimum alveolar
wall thickness value for the adult human is 10 m [26].
10
Discussion
The fundamental frequencies of the square membrane model of alveolar wall for adult mouse
and human is determined to be within the diagnostic US frequency range. The threshold
pressure equation developed here for the square membrane model of the alveolar wall, is for
the fundamental mode only. Beards [27] states that if a structure can survive the fundamental
mode resonance, it will be able to survive the other resonance mode too (at that same
frequency values). Thus, the study of the threshold pressure at fundamental mode of the
square membrane model of alveolar wall is sufficient enough for determining the theoretical
occurrence of US-induced lung haemorrhage.
The alveolar wall thickness and size varies in species. According to this study, the threshold
pressure for US-induced lung haemorrhage depends primarily on the species alveolar wall
thickness. ECMUS [4] supports these findings by stating that US-induced lung haemorrhage
depends on the species of animal.
The Fig. 3 shows that if diagnostic US imaging for humans is kept above 1.69 MHz, the US
induced lung haemorrhage will not occur when MI < 1.9. This support the result of the single
study of the US induced lung haemorrhage on human [3]. The US medical imaging in the
abdominal and thoracic regions, utilizes the frequency of > 2 MHz [28, 29]. Hence, the USinduced lung haemorrhage is prevented during diagnostic US imaging of the adult human if
the FDA regulation of MI < 1.9 is obeyed.
The chi-square comparison test in Fig. 2, show that the square membrane model of the
alveolar resonance to be acceptable with 95% probability. The square membrane model is
found valid and describes the US induced lung haemorrhage adequately. Therefore, the
11
alveolar resonance mechanism can be duly considered as a serious candidate mechanism for
the US-induced lung haemorrhage based on the theoretical validation of this membrane
model.
The alveolar wall was assumed as square membrane with fixed boundary. In reality, the
alveolar wall borders are supported but the shape is pentagonal, and so the results in this study
might vary somewhat. The alveolar wall was further assumed to be isotropic and linearly
elastic. This is valid as alveolar wall contains elastin fibres while the occurring strains are
small.
Conclusions
Square membrane model of the alveolar resonance mechanism is shown to be theoretically
valid. Therefore, the alveolar resonance mechanism explains adequately the US-induced lung
haemorrhage. According to this study, the US-induced lung haemorrhage do not occur in
human at >1.69 MHz if MI is < 1.9.
Appendices
Appendix A: The Q-factor of support of the square membrane
The support loss Q-factor for square membrane when support is semi-infinite large body as
according to Naeli & Brand [30];
Q support
= 0 . 34 ( L / d ) 3
The side-length is L and the thickness is d. If the support is as thin as the membrane (as in
alveolar wall where its support comes from adjacent alveolar walls), then the cubic term
12
becomes linear. This is because the support is not rigid and isolated anymore against in-plane
bending of the resonator [31].
Q support
= 0 . 34 ( L / d )
= ( L1 L 0 ) / L 0
The areal strain that quantizes the surface distortions is;
= ( A1 A 0 ) / A 0
The initial length and area are L0 and A0 respectively while the length and area after
deformation are L1 and A1, respectively. The relation between areal strain and linear strain can
be obtained starting with the stretch ratio equation. The stretch ratio is [32];
= ( L 1 / L 0 ) = ( A1 / A 0 )
Thus the relationship between linear strain and areal strain can be derived as;
= ( A1 / A 0 )
1 = ( + 1) 1
= ( + 1) 1
During normal tidal breathing, the linear strain changes between 0 < < 0.05 [10]; and so the
areal strain of tidal breath is;
0 0.05
0 [( + 1) 1] 0.05
0 0.1025
13
The wounding and breaks in cells in the plasma membrane of the alveolar epithelial cells
occurs at the yield linear strain of = 0.08 [11, 12]. Thus the yield areal strain is;
= 0.08
[( + 1) 1] = 0.08
= 0.1664
The data is obtained from Church & OBrien WD [1] and tabulated in Table 1.
References
[1] C.C. Church & W.D. Jr. OBrien. Evaluation of the threshold for lung hemorrhage by
diagnostic ultrasound and a proposed new safety index. Ultrasound Med Biol. May 33(5)
(2007) 810-8.
[2] A.F. Tarantal & D.R. Canfield. Ultrasound-induced lung hemorrhage in the monkey.
Ultrasound Med. Biol. 20(1) (1994) 65-72.
[3] R.S. Meltzer, R. Adsumelli, W.H. Risher et al. Lack of lung hemorrhage in humans after
intraoperative transesophageal echocardiography with ultrasound exposure conditions similar
to those causing lung hemorrhage in laboratory animals. J Am Soc Echocardiogr. 11(1)
(1998) 57-60.
[4] European Committee for Medical Ultrasound Safety (ECMUS). EFSUMB Tutorial:
Acoustic cavitation and capillary bleeding. European Journal of Ultrasound, vol.9 (1999) 277280.
[5] L.A. Frizzell, J.F. Zachery & W.D. Jr. OBrien. Effect of pulse polarity and energy on
ultrasound-induced lung hemorrhage in adult rats. J. Acoust. Soc. Am. 113 (2003) 2912-2918.
14
[6] C.H. Raeman, D. Dalecki, S.Z. Child et al. Albunex does not increase the sensitivity of the
lung to pulsed ultrasound. Echocardiography 14 (1997) 553-557.
[7] C.C. Church, E.L. Carstensen, W.L. Nyborg et al. The risk of exposure to diagnostic
ultrasound in post-natal subjects-nonthermal mechanisms. J. Ultrasound Med 27 (2008) 565592.
[8] A.A. Vivino, D.K. Boraker, D. Miller et al. Stable cavitation at low ultrasonic intensities
induces cell death and inhibits
15
[17] J. Mead, T. Takishima & D. Leith. Stress distribution in lungs: a model of pulmonary
elasticity. J. Appl. Physiol. May;28(5) (1970) 596-608.
[18] W.C. Elmore & M.A Heald. Physics of waves. Dover Publications Inc, 1985.
[19] H. Bachmann, W.J. Ammann, F. Deischl & J. Eisenmann. Vibration Problems in
Structures: Practical Guidelines. Birkhauser Verlag, Berlin, 1995. ISBN-13: 978-3764351489.
[20] A. Sinha. Vibration of Mechanical Systems. Cambridge University Press Cambridge,
New York, 2010. ISBN-13: 978-0-511-77527-7
[21] K.K. Park, H. J. Lee, P. Crisman et al. Optimum design of circular CMUT membranes
for high quality factor in air. IEEE International Ultrasonics Symposium Proceedings (2008)
504-507.
[22] S. Frew, H. Najar, E. Cretu, VHDL-AMS Behavioural Modelling of a CMUT Element E.
Behavioral Modeling and Simulation Workshop (BMAS), IEEE (2009) 19-24.
[23] D.J. Jabaraj & M.S. Jaafar. Theoretical calculation of resonant frequencies of the human
alveolar wall and its Implications in ultrasound-induced lung haemorrhage. Inter. Journal of
Bioscience, Biochemistry and Bioinformatics (2013);3(1):5-9.
[24] P.M. Treuting & S.M. Dintzis. Comparative Anatomy and Histology: A Mouse and
Human Atlas. Academic Press; 1 edition (December 30, 2011) ISBN-13: 978-0123813619
[25] G.D. Ludwig. The Velocity of Sound through Tissues and the Acoustic Impedance of
Tissues. J. Accous. Soc. Am. v 22, (1950) 862-66.
[26] H.S. Choi, Y.G. Ko, S.K. Seol et al, Early detection of intralveolar wall thickening
induced by intestinal ischemia/perfusion injury in mouse lungs by using phase-contrast x-ray
microtomography. The 13th international conference on accelerator & beam utilization
(Synchrotron Bio & Medical application) 2009.
[27] C.F. Beards. Structural Vibration: Analysis and Damping. Butterworth-Heinemann; 1st
edition (June 14, 1996). ISBN 0 340 64580 6
16
[28] V. E. Noble. Think Ultrasound When Evaluating for Pneumothorax. J Ultrasound Med.;
31 (2012) 501504.
[29] R.J. Fitzgibbons & A.G. Greenburg. Nyhus and Condon's Hernia. Lippincott Williams
& Wilkins; 5th edition (November 15, 2001) ISBN-10: 07817196232001.
[30] K. Naelia & O. Brand. Dimensional considerations in achieving large quality factors for
resonant silicon cantilevers in air. J Appl. Physics 105 (2009), 014908.
[31] M.C. Cross & R. Lifshitz. Elastic wave transmission at an abrupt junction in a thin plate
with application to heat transport and vibrations in mesoscopic systems. Physical Review B
vol. 64 (2001) 085324.
[32] A. Gefen, D. Elad, R.J Shiner. Analysis of stress distribution in the alveolar septa of
normal and simulated emphysematic lungs. J Biomech. 1999 Sep;32(9):891-7.
Tables
Table 1: Selected lowest threshold pressure at certain frequencies of the US-induced lung
haemorrhage experimental data for adult mouse from the compiled data by Church & OBrien
WD [1].
Adult Mouse
Frequency (MHz)
1.1
1.2
1.2
2.3
2.3
2.3
2.8
3.5
3.7
3.7
5.6
17
Figure Captions
18
experimental data
7.00
6.00
5.00
4.00
3.00
2.00
1.00
0.00
0.00
1.00
2.00
3.00
4.00
5.00
6.00
7.00
8.00
9.00
10.00
Fig. 2: The threshold pressure vs. fundamental frequency curve of the square membrane
model of adult mouse alveolar wall together with the plotted past experimental data of
ultrasound induced lung haemorrhage in the adult mouse [1]. An experimental data point (2.8,
3.6) is clearly an outlier and hence is omitted in the chi-square calculation. Chi-square (2) of
experimental data against the square membrane model is below the critical 2 (0.05 sig.).
19
MI=1.9
3.50
3.00
2.50
2.00
1.50
1.00
0.50
0.00
0.00
0.20
0.40
0.60
0.80
1.00
1.20
1.40
1.60
1.80
2.00
Fig. 3: The threshold pressure vs. fundamental frequency curve of the square membrane
model of adult human alveolar wall together with the plotted MI = 1.9 limit line.
20