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were intended to avoid thermally significant cavitation. This , M E?‘ l 1" §,\ ‘ l .;_7._;  '
example shows the potential for real-tirne mapping of bubble '- \""‘,4t;   9 E - _ 3-,. »
activity in clinically relevant targets using PAM techniques. , mm A E  ;“‘-2 ‘Lift; '1

. \ _' e.
Using Bubbles ' ’ ‘” " "5 " "‘"'  ‘ ' '
Bubble Behaviors Figure 3. Example of passive cavitation mapping during a clinical
The seflnmgly simple sysmm of an “1u.asomca]_1y dn-ven therapeutic ultrasound procedure. Lefi: axial CT slice showing tho—
bubble in a homogeneous liquid can exhibit a broad range raeie organs, including the tumor targeted for treatment, with real
. . . and lrlue arrows indicating the directions of therapeutic foevseiz
°f "“h“"‘°“ (F‘%“" 4)‘ I“ ““ ““'’°““d‘*d ’“°d‘““‘* "“""1“ ultrasound (pus) ineialenee and PAM data eolleetion, respectively.
wall motion induces fluid flow, sound radiation, and heating R,-KM. mlmged Suheg,-0,, (143, Hue dushzdfifl box) in which a
(Leighton, 1994) and may spur its own growth by rectified PAM image was generated. Maximum (red) and minimum (blue)
diffusion, a net influx of mass during ultrasonic rarefaction color map intensities cover one order of magnitude. A video of six
cycles. When a bubble grows sufliciently large during the rar- 5"‘595_5iV9 Pf’“’“95 5P“’_‘"i"Z '1 “W11 "me P9’il"1 °f500 mi"'9595’
efactional half cycle of the acoustic wave, it will be unable to “"15 ‘S avmlame ut mmujnfimduy‘mg/gmy‘mzdm)'
resist the inertia of the surrounding liquid during the com-  
pressional half cycle and will collapse to a fraction of its orig- ungm seal. a ‘
inal size. The resulting short-lived concentration of energy    . 3 5
and mass further enhances sound radiation, heating rate, fluid  /‘  $.54 ., ..,. ,, ., .
flow, and particulate transport and can lead to a chemical reac-  V  - ta’   ‘ \‘;’_.\
tion (sonochemistry) and light emission (sonoluminescence). /-’  " i‘ _.
Regarding the spatially and temporally intense action of this // //'  mi  \_> i .2
“inertial cavitation,” it has been duly noted that in a simple ‘ll’ /" g s‘ 1. os:::' '
laboratory experiment “ can create the temperature of i’ ll ;";'::ei  ._
the sun’s surface, the pressure of deep oceanic trenches, and   ' , ""' 
the cooling rate of molten metal splatted onto a liquid-helium-  ‘ >:_,,ulVAl‘"‘V:‘‘‘mLE ‘ us.‘
cooled surface!” (Suslick, 1990, p. 1439).  ».\ ,>:‘Vi;\rV\\ .-’ /, Mn  .
. -. 1w . , r .-
Further complexity is introduced when the bubble vibrates near ‘z\ \\ ”" " ’ -~ ..  -' ii"
an acoustic impedance contrast boundary such as a glass slide in \\ ‘x\ H ‘V /v“ 
an invitro experiment or blood vessel wall in tissue. Nonlinearly ‘\\ m‘ ""   U /- ‘la?
generated circulatory fluid flow known as “microstrea.ming” is ‘\.., __ C Q; //
produced as the bubble oscillates about its translating center H 7‘ V % E‘ _
of mass (Marmottant and Hilgenfeldt, 2003) and can both en- ‘
hm“ "”“P°“ °f “why ‘h°”P’“““ Pmid” (dmgs °' ‘“b' Figure 4. Illustration of bubble ejects and length scales. Green, in
’“iC‘°“ ““°1ei) “mi MPMY ‘Md She” “C5595 ‘h“‘ d°f°"“ °' vivo measurement feasibility; jagged shapes indicate reliance on iner—
rupture nearby cells (“microdeformation" in Figure 4). tial cavitation; red aim, lrest spatial resolution; text around radial
Th '1, A ucafions-_ arrows, demonstrated noninvasive observation methods. SPEC7:
"”“""‘ f P1’ , single photon emission computed tomography; US, ultrasound; a, an
F"’""“’ M“‘"’ ‘W’ 5"‘1"’B""""-‘ tive; 12, pamive; MRI, magnetic resonance imaging; CT, X—ray eom—
Suitably nucleated, mapped, and controlled, all of the aforernen- puted tomography; PET, positron emission tomography.
tioned phenomena find therapeutically beneficial applications
within '_'he human body'_ Hére‘ “re prefer“ 8‘ s“bS_€t °fl'he_ev“- tion depth, optimally achieved at lower frequencies, and the
expanding range of applications mvolvmg acoustic Cavmmon local rate of heating, which is maximized at higher frequen-
One of the earliest, and now most widespread, uses of thera- cies. “Furnace” bubbles provide a unique way of overcoming
peutic ultrasound is thermal, whereby an extracorporeal this limitation (Holt and Roy, 2001); by redistributing part
transducer is used to selectively heat and potentially destroy of the incident energy into broadband acoustic emissions
a well-defined tissue volume (“ablation”; Kennedy, 2005). A that are more readily absorbed, inertial cavitation facilitates
key challenge in selecting the optimal acoustic parameters to highly localized heating from a deeply propagating low-fre-
achieve this is the inevitable compromise between propaga- quency wave (Coussios et al., 2007).
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