Robert K. Zeman, MD Wendelin S. Hayes, DO Cirrelda J. Cooper, MD

#{149} William #{149} Paul

Cavitation Part

effects

lithotripsy

can

cally

visible

Davros, L. Cattau, M. Silverman,

Effects

II#{149} Clinical

Cavitation

during produce

The

fragmentation Microbubble

re-

in 31 of forma-

tion in the liver correlated with transient hepatocellular damage (as indicated by a twofold rise in serum transaminase levels) immediately after seven of 10 treatments. Advancing the focal volume of the deeper

(placing the stone point of the focal useful strategy for cavitation effects, be responsible for tocellular damage.

into

during

C

biliary sonographi-

microbubbles.

lithotriptor

terms:

the

patient

at the proximal zone) may be a reducing hepatic which appear to temporary hepa-

Gallbladder, 762.1299

#{149} Lithotripsy,

interventional

Radiology

1990;

calculi,

762.289

procedure. 762.1299

177:163-166

is increasingly clear that cavitation contributes to stone fragmentation (1,2) and perhaps even to tissue injumy (3), clinical data linking stone fragmentation, tissue injury, and the presence of sonogmaphically visible microbubbles during lithotnipsy are sparse. To obtain such data, sonographic evidence of the location, intensity, and power level at onset of it

cavitation bbes were outcome treatments.

MATERIALS

AND

in

during

The

13 men

years. two

for

more

three than

stone

mm

for

From the Departments of Radiology (R.K.Z., W.J.D., JAG., B.S.G., W.S.H., S.C.H., CC., P.M.S.) and Medicine, Gastroenterology Division (E.L.C.), Georgetown University Medical Center, 3800 Reservoir Rd NW, Washington, DC 20007. From the 1989 RSNA scientific assembly. Received February 5, 1990; revision requested March 16; revision received April 4; accepted April 17. Address reprint requests to I

in age

stone,

three

diameters stones

4

22 to 71 initially

ranged

more

in-

from

The

than

R.K.Z. 1990 by Zeman et al (pp 157et al (pp 147-151), and Shapiro (pp 153-156) in this issue.

and

treatment. probe

top)

real-time

diame-

is also position

the for

imaging

is used

22,

left the

used. was

The used

posterior supine

an

for two,

for

taken

to 1ev-

patient

data.

and

recorded.

the

procedure

were

used

The

formation

targetable Real-time

procedure

were

during

and

to gener-

locations

of mi-

(subcutaneous

tis-

bile, vessels, and were recorded.

bubbles,

2

city, city, city 5 =

moderate

3 = 4 = with

others) and Microbubble

tar-

25 treat-

(to table

microbubble

echogeni-

microbubble

persistent

shadowing

beyond was divided microbubble

We called this the If no microbubble maximum

echogeni-

and

prolonged

30 seconds). by the power formation

“cavitation formation

energy

was

The level appeared.

quotient.” occurred,

achieved

used

at

as the

for

that

denominator

for

the quotient calculation. The cavitation quotient differs from the microbubble intensity index used in our previous in vitro work in that it is depen-

dent

on the

power

increases

during

level in

fact

that

were

proapplied

the quotient stones

re-

exposed

level

at

ex-

power

level

(low

to long

cavitation onset) may undergo different degrees of fragmentation than stones posed to shorter periods of cavitation (high

of cavitation

(1). Because

power

the treatment, the

periods

de-

faint

=

intense microbubble echogeniintermittent shadowing, and intense microbubble echogenicity

which

flects

lateral

and

entire

of videotapes

gnessive

during

oblique for

mo-

out-line left

by

unless no was visible.

images

cavitation

the

during

viewing

tolerated

of the

treatment

presto 7.5 as a

unit has sector-scan

imaging

tangential

treatment ments,

1 to 9. The

A 3.5- or 5.0-MHz for

cubitus

be

shock waves on fragment

grade

performed with the Plus (Siemens Medical

mechanical probe that

to let de-

the

could

dissipation

7 to 45 in

suspend-

case

el that

with

cumula-

from 5 mm

was

in each

intensity was graded by consensus of two observers (R.K.Z., W.J.D.) who did not know treatment outcome (1 no micro-

22 treatments

stones.

Treatment

dissipate power

crobubble

were and

was to target the more than 5

bnis settle and microbubbles assist in targeting. The highest

ate

10 treatments

stones,

linear scale from in-line, 3.5-MHz ultrasound (US) geting

diameter.

Notes

16 women

treatments

for one or

tive

in

strategy on fragment

ed up to 5 minutes

review

at our

were

ranging

performed

initial

operation

patients

Eighteen

for

mm

to release excessive hair shaved to en-

contact.

treatment stone

freeze-frame

29 patients

the

of lithotnipton

stitution. and

good

The largest

US

METHODS

of 50 treatments

performed

months

sure

sues, liver, its intensity

Systems, Iselin, NJ). The “overhead dule” used for treatment generates sures from 220 to 750 bar (2.2 X i0 x iO Pa). Power levels are expressed

161), Khouri and Winsberg

MD

contact pressure was required shock waves. Patients with over the coupling site were

4,000 stone

manifesting as microbubcorrelated with the clinical of 50 gallstone lithotnipsy

Lithotnipsy was Siemens Lithostar

RSNA.

S. Garra,

was achieved by progressively increasing the setting at intervals of 50 shock waves. Treatment was extended to a maximum of

ten.

See also the articles

#{149} Brian

Lithotripsy

effects produced by shock waves occur in a variety of media (1). In the laboratory, stones surrounded by fluid capable of supporting cavitation appear to fragment more thoroughly than stones embedded in a solid medium (1). Although

A total

Gallbladder,

RN MD

AVITATION

were Index

PhD #{149} Jo Anne Goldberg, Jr, MD #{149} Steven C. Horii, MD

Observations’

lationship between microbubble formation and clinical outcome of gallstone lithotripsy performed with a commercial lithotriptor was studied in 50 treatments in 29 patients. Microbubble formation in bile was a useful predictor of successful stone 34 treatments.

J.

#{149} Edward

at cavitation

power

onset).

A

the

semierect for one. The largest coupling surface that was anatomically possible was used. A minimum of 9 lb (4.1 kg) of

Abbreviation: oxaloacetic

SGOT

serum

glutamic

transaminase.

163

large cavitation quotient microbubble formation tively

low

power

implies

violent

occurring

levels,

at rela-

while

a small

quotient implies meager bubble formation despite relatively high power levels. The cavitation quotient for bile was correlated with the occurrence of stone fragmentation. A 50% reduction in stone diameter was required to label fragmentation successful. A hepatic cavitation quotient was also calculated when microbub-

a.

bles

Figure

were

seen

to accumulate

parenchyma. tient was

The hepatic correlated with

in

glutamic

serum

in

the

liver

cavitation quothe difference

oxaloacetic

transami-

nase (SCOT) levels immediately before and 2 hours after lithotnipsy. Subjective procedural observations were also recorded as they related to attempts to manipulate cavitation effects.

RESULTS Successful fragmentation (50% reduction in stone size) occurred in 34 of 50 treatments. Of the 16 treatments with unsuccessful fragmentation, five produced no fragmentation. Because the treatments were consistently structured to target the largest stone and success was determined by a 50% reduction in the size of that stone, there was no significant difference in stone burden for the fragmentation group versus the group with unsuccessful fragmentation. The mean number of stones was 3.0 ± 2.0 in the fragmentation group and 3.1 ± 1.9 in the unsuccessful fragmentation group. Similarly, the cumulative diameters of the stones in each group did not differ significantly (23 mm

±

8.8

vs

24

mm

±

11,

b.

ing

1.

Cavitation

lithotnipsy

illustrate

c.

the rapid

gallbladder. development

sipated. rolling

A small fragment the patient and

(arrow) separating

has the

time

ranging

utes.

No

were

seen

from

40 seconds

residual

in the liver

patients. An elevation el to twice the baseline in

seven

of

of these

of the value

SCOT 1evwas seen

10 treatments

that

one

of 40. In Figure

tation

quotient

5, the hepatic

is plotted

in SCOT

Figure

gree

of microbubble

SCOT

level

with

a coefficient suggests

shock

and

the

formation

164

#{149} Radiology

by

damage.

In seven

2 weeks

after

three, bles

of the eight

were seen in hepatic patients (Fig 6). In all

concomitant were

between

hepatic

present.

A clear

the hepatic

focus

microbubbles

traveled

images

showed

entered

as a parabolic

(arrow)

wave

path

bubbles

appeared

became

barely

shock

wave

forming

to the

a dense along

visible was

each

These

shock

by the time

of

the

in the gallbladder. with

shock

band

wave

and

the next

applied.

QUOTIENT

CAVITATION

Figure 3. cavitation tionship

RANGE

Histogram displays gallbladder quotient ranges and their relato fragmentation (FRAG).

connection

of bubbles

that

the

shows

microbub-

and the vessel was identified in two of the three cases. On the basis of their distribution, the vessels were branches of the portal vein in two cases and of the hepatic vein in one case. Review of

videotape

confined

US image

patients

lithotnipsy.

Microbubbles vessels in three

Cavitation

de-

with elevated SCOT values, the values returned to within 10 U of baseline by

ments and sludge. They could be distinguished because, with pauses in treatment, microbubbles tend to rise to the nondependent surface of the gallbladder and then collapse, losing their transient shadow. As they dissipate, bubbles do not form an echogenic layer along the dependent portion of the gallbladder, whereas fragments do. The intensity of microbubble formation and the power level at onset were useful predictors of fragmentation. The cavitation quotient was less than 1.5 in all patients in whom successful fragmentation was not achieved (Fig 3). In patients with successful fragmentation, a broad range of quotients existed, from 0.1 to 5.0. Microbubbles appeared as bright “flashes” within bile, lasting less than 1 second in 29 treatments. In

confirmed

in the

were

frag-

was

of .79.

that

liver and whether it occurs early in the treatment (at low power) are predictive of the extent of transient hepatocellulai

stone

This

The in the

the 36 treatments in which microbubbles occurred, 32 showed bubbles prior to any significant gallstone fragmentation. In four treatments, microbubbles

with

path.

microbubbles

the

before

2.

wave

cavi-

against

values

showed

along

stone.

showed

hepatic microbubbles. In the 40 treatments with no visible hepatic microbubbles, a rise in the SCOT level to twice the baseline value was seen in

correlation

present

the

changes

of any

This

Of

off

to 6 mm-

sonographic

after lithotnipsy for all treatments. quotient correlated with the rise

formation.

been chipped two fragments.

of 50 shock gives rise to indisthe cloud has dis-

seven treatments, progressive buildup of bubbles was seen. The dissipation time of these bubbles ranged from 30 seconds to 3 minutes. Microbubbles were identified within the liver panenchyma during 10 treatments (Fig 4). Temporarily stopping the treatment caused microbubbles to disappear in all 10, with the dissipation

Microbubble formation within the gallbladder was identified in 31 of the 34 successful treatments (Figs 1, 2). Of the 16 unsuccessful treatments, 11

no microbubble

Sequential US images of the gallbladder dunand dissipation of microbubbles. (a) Baseline

image shows a solitary stone targeted in the crosshains. (b) After application waves (1 minute), a cloud of microbubbles (arrow) obscures the stone and tinct shadowing. (c) One minute later (after stopping of the shock waves),

difference

respectively).

within the

vessel,

cluster

once

the

they

in the di-

rection of flow. The bubbles appeared to be tightly clustered as they entered the vessel but spread to fill the vessel as they moved downstream. The rate of bubble travel ranged between 5 and 10

mm per ‘/30-second video frame. After approximately the 40th treatment, concerns that cavitation may be related to temporary hepatocellular injury

and

attenuate attempts

was

found

that

hepatic

microbubbles

may

the shock waves resulted to limit hepatic cavitation.

that

cavitation

in It

in the liver

could be reduced by stopping the treatment, changing the shock wave path, or moving the proximal edge of the focal zone deeper into the patient (ie, placing the stone at the proximal point

October

1990

150

I y=

I R=0.79

-3.9732+40.5781x

a)

U

100

-

-

-

U)

-

0

cn

El-

--

--. -

I-

0 0

.

U)

a.

b.

v

(

A

1’

c.

Figure 4. Microbubble development in the liver, shown on sequential US images. (a) Baseline view shows a solitary stone in the gallbladder. The liver is in the near field and shows no abnormality. (b) After application of 1,000 shock waves, progressive microbubble formation (curved arrow) is seen in the liver. A dense acoustic shadow is cast across the gallbladden (gb), which is filled with sludge, fragments, and cavitation bubbles. (c) After stopping of the shock waves, the hepatic microbubbles dissipated oven 3 minutes.

-

-

-

-

-

0

1

Cavitation Figure rise

5.

Quotient

The relationship

in SGOT

level

and

hepatic

strategy

zone)

reduced

formation eliminated

(Fig

7). The

hepatic

during

two

latter

burden by performing and evaluating success

microbubbbe

treatments

and

it in one.

DISCUSSION It was shown previously that acoustic cavitation may be produced by extracorporeal shock wave lithotnipsy (4). Our work shows that microbubbles resuiting

from

cavitation

are

readily

seen

at neal-time US during clinical gallstone lithotnipsy. Their presence may be noted not only in bile but also in soft tissue such as liven Limited stone size and

previously predictors Our work absence of

been suggested as the only of successful lithotnipsy (5). suggests that the presence or microbubbles in bile during

lithotnipsy

marker

may

that

mentation.

Volume

parenchyma. number have

We

177

be used “factored

#{149} Number

out” 1

majority

of

of our

can be seen

(curved

treatments.

rising

away

arrow),

but spread paraimages was ‘to

The

bubbles

from

the bile-

cavitation

occurs.

50% fragmentation of the largest targeted stone. Although the presence of bubbles does not uniformly predict that stones will break, successful pulvenization is far less likely if intense microbubbles do not form at relatively low power. It should be noted that both in the laboratory and in our clinical expenience some stones broke in the absence of obvious microbubbles (1). Pul-

stone

interface

Once

significant

venization appears less complete, however, when cavitation is not optimized

time sonographic observation will show that bubbles give rise to a rapid sequence of events: a bright echogenic flash that disperses centrifugally and disappears prior to the arrival of the

(1,2). During clinical lithotripsy, ous echoes are seen within recently suggested on the

tro data

that

gallstone

microbubbles

fragments

(1,6).

numerbile. It was basis of in vi-

may This

mimic did

not

of frag-

pose a problem in the calculation of the cavitation quotient, in that microbubble intensity was graded prior to signif-

stone

icant

as an important

can be predictive

our treatments on the basis

the

cavitation

quotient.

Figure 6. Microbubbles within hepatic vessels. The sequence of US images shows a collection of microbubbles in the liver which escape into a branch of the portal vein (straight arrows). The bubbles at first are a dense focus as they enter the vessel bolically to fill the vessel with low-intensity echoes. The direction of flow is to the reader’s left. (The time interval between second.)

of the focal

(Liver)

between

stone

fragmentation

in the

vast

when

numbers

of fragments

and sludge exist within the gallbladder, differentiation of microbubbles is difficult but not impossible. If one temporanily suspends shock wave generation, microbubbles are seen to rise, while the fragments “rain down” to form a layer along the dependent sun-

face of the gallbladder.

next

shock

wave.

Careful

This

was

seen

real-

in all

36 treatments in which there was microbubble formation and is analogous to what is seen during a fireworks display. A fragment would not repetitively

out,

give

and

rise

to an

disappear

intense

every

echo,

spread

0.83

seconds

Radiolotv

#{149} 165

(the

interval

between

the same location. ally at the conclusion

that

microbubble

debris-filled

waves)

is so

crete microbubble identified.

that

dis-

cannot

be

quotients

presented

here represent calculations that unique to our machine. Despite subjective nature of the quotient, provides confirmation who have bile that

that readily

low power

levels

show

more

significant

tation

than

late

cavitation

future

work

tionship targeting

the it at

likely

to

Figure

stone

fragmencavitation at the

with

levels know

only. how

effects

within

may

are

patients cavitates

are more

those

highest power yet specifically

(usu-

in viscous

great

bursts

cavitation

in

are times of a treatment)

persistence bile

The

shock There

shed

We do not to manipubile,

light

on

but

the

rela-

between bile composition for optimal cavitation.

and

Delius et al suggested that cavitation may have been responsible for soft-tissue injury in experimental studies in dogs (3). Similarly, Kuwahara et al showed that hypenechoic foci indicative of micnobubbles correlate with histologic evidence of injury to the canine

kidney

during

(7). On

the

pears

that

experimental

basis tissue

lithotripsy

of these

studies,

tolerates

it ap-

compressive

forces better than rarefactive forces. Our work clinically confirms the expenimental hypothesis of Delius et a! and Kuwahara et a! in liver parenchyma of patients undergoing gallstone

lithotnipsy.

Transient

liver

injury,

as

evidenced by a reversible rise in the SCOT level, was clearly associated with the presence of hepatic microbubbles. The microbubbles were usually shortlived but persisted as long as 6 minutes in liven parenchyma. This dissipation time was greater than in bile and probably related to the solid nature of liver parenchyma. No residual sonognaphic changes were identified in the liver of any patient. Hepatic microbubbles in the near field often cast their shadow across the target zone within the gallbladder. Not only may targeting be impaired but we hypothesize that shock waves may be attenuated. Because of concerns about transient hepatocellular damage and potentially compromised treatments, strategies for

limiting oped. ment

they

liver

cavitation

Temporarily causes bubbles

recur

when

were

devel-

stopping the to dissipate,

treatment

treatbut

is resumed.

Redirecting the shock wave path can shift the location of tissue injury. If the path remains transhepatic, cavitation is not reduced but merely moved. Advancing the center of the focal volume

deepen

into

the

patient

proved

to be the best strategy for reducing liven cavitation. This can usually be accomplished by extending the Lithostar acoustic lens but may at times require

166

Radiology

#{149}

7.

Schematic

shows

how

focal

volume

is advanced

into

patient

to limit

hepatic

cavi-

tation. Although the overall shape of the shock wave beam is that of an hourglass, the twodimensional representation of the focal volume (50% isobar) is cigar shaped (series of dots). With extension of the acoustic lens from the lithotripton, the focal volume may be moved deeper into the patient. This places the stone at the proximal point of the focal volume and the liver in a lower-power portion of the beam. If properly targeted, the stone will attenuate far-zone power, and the beam may be angled to avoid the upper pole of the right kidney. GB = gallbladder, dashed line skin surface, cross-hatched area hepatic cavitation.

the compression pressure at the coupling site. Since the focal volume tends to be cigar shaped, it is pos-

away microbubbles er parenchyma

sible

In conclusion, sonographically visible microbubbles in bile are an important marker of cavitation and enable

varying

to advance

the focus

so that

the

stone resides at the proximal point of the focal zone (Fig 7). The power delivered to the stone in the near-field portion of the focal volume is only slightly reduced compared with that in a more

central

portion

of the focal

volume.

Ad-

vancing the focus leaves the liver antenor to the focal volume, in a wider, less powerful part of the beam, resulting in fewer cavitation effects. This approach to clinical targeting is useful but should be used only if the far zone of the shock wave path can be angled to avoid the kidney. Advancing the focus to spare the liver while jeopardizing

the kidney

is not acceptable.

not be necessary devices

(mainly

small

and

round

with

or elliptic

a

echoes

are

disturbance

caused

The

and

pattern

due by

rate

solely the

of flow

to

shock

flow waves.

foci in the livliver from

stone pulverin liven may

cause transient hepatocellular damage. Advancing the focal zone and altering the shock wave path may be useful in reducing intrahepatic cavitation. U Acknowledgments: The authors acknowledge Karen Kellough and Yvonne Carew for assistance in the preparation of this manuscript.

References 1.

2.

3.

4.

5.

focus.

Vascular microbubbles were seen in three patients. In all three, a focus of hepatic microbubbles was seen near the vessel, and in two, bubbles could be seen entering the vessel. This latter observation makes it unlikely that intravascular

prediction of successful ization. Their presence

at all for low-power piezoelectnic)

the

injury.

Manipula-

tion of the focal zone depth to reduce cavitation in critical organs is possible regardless of the method used to actually generate shock waves. The maneuyen is most useful for devices with cigar-shaped focal volumes that have an axial dimension larger than that of many stones and which may overlap adjacent organs. The maneuver may

from protect

Zeman RK, Davros WJ, Garra BS, Horii SC. Cavitation effects during lithotnipsy. I. Results of in vitro experiments. Radiology 1990; 176:000-000. Delius MK, Brendel W. Mechanisms of action in extra-corporeal shockwave lithotnipsy. In: Ferrucci JT, Delius MK, Burhenne HJ, eds. Biliary lithotnipsy. Chicago: Year Book Medical, 1989; 31-42. Delius M, Jordan M, Eizenhoeffer H, et al. Biological effects of shock waves in dogs: administration rate dependence. Ultrasound Med Biol 1988; 14:689-694. Coleman AJ, Saunders JE, Crum LA, Dyson M. Acoustic cavitation generated by an extracorporeal shockwave lithotripter. Ultrasound Med Biol 1987; 13:69-76. Sackmann M, Delius M, Sauerbruch T, et al. Shockwave lithotnipsy of gallbladder stones: the first 175 patients. N EngI J Med 1988; 318:393-397.

6.

7.

Brink JA, Simeone JF, Saini S. et al. Simulation of gallstone fragments by cavitation bubbles during extracorporeal shockwave lithotnipsy: physical basis and in vitro demonstration. Radiology 1990; 174:787-791. Kuwahara M, loritani W, Kanibe K, et al. Hyperechoic region induced by focused shockwaves in vitro and in vivo: possibility of acoustic cavitation bubbles: J Litho Stone Dis 1989; 1:282-288.

suggested

that the microbubbles were entering venous structures. The vessel distnibution allowed us to confirm that the yessels in two of three patients were branches of patients to ascertain

of the portal vein. is still too small whether vessels

This group to allow us carrying

October

1990