THE
JOURNAL
OF
ACOUSTICAL
THE
SOCIETY
OF
AMERICA
Volume
25I• Number
1
JANUARY
ß 1953
Symposium on Ultrasound in Biology and
Medicine, University of Illinois, May 1952
The firstfourpapersin thisissueconstitute
a partialreportof a symposium
on Ultrasound
inBiology
andMedicine
heldat theUniversity
ofIllinoisinMay,1952.Thefollowing
2 paperspresented
at thissymposium
arenot asyet readyfor publication
andwill appear
in a later issue:
The Useof High IntensityUltrasoundin ExperimentalNeurology.P. D. WALL,D. TUCKœR,
F. J.
FRY, AND W. H. MOSBERG,JR.
The Effects of BiologicalTissues on l$-mc Pulsed Ultrasound. J. J. \Vn.D Axn J. M. REIn.
Action of Ultrasound on Nerve Tissue--a Review*t
WILLbXU J. FRY
Universityof Illinois, Urbana, Illinois
(ReceivedSeptember19, 1952)
This review is concernedwith (1) certain physiologicaland
structural changesproducedin tissuesof the central nervous
systemcausedby high level ultrasoundand (2) investigations
into the physicalmechanisms
underlyingthesechanges.
The cell bodiesof neuronsin the central nervous systemare
particularly susceptibleto changeby ultrasound.The effect of
irradiationis immediatelyevidentas a lossof functionwhich may
be reversibleor irreversibledependingon the dosage.Irreversible
changesin functionare accompanied
by changesin the structure
of the cell. The susceptibilityof neuronsstudiedso far is graded
accordingto size, the larger neuronsexhibitinga greater susceptibility. The doseof ultrasoundcan be adjusted to causeirreversible changes in neurons without causing any observable
damageto the vascular
andsupporting
components
of the tissue.
Thisselective
andspecific
effectof ultrasound
is beingusedasa
tool in neuroanatomical
studiesnow in progressand has considerablepotentialvalue in neurosurgery.
The ultrasoundalters
the state of the nervecellsand, therefore,affordsa basisfor
studyingintracellularstructureand function.
The physical
basisfor the ultrasonically
produced
biological
effectshasbeeninvestigated
in part. The following
aspects
of
temperature
havebeenanalyzed
andrejected:(1) High average
(space)
level,(2) interface
heating,
(3) rapidtimerateof change,
(4) temperature
changes
resulting
fromcavitation,
(5) heating
at
gasnuclei.The phenomenon
of cavitationis alsoshownto play
no essentialdirect role in producingthe effects.
I. INTRODUCTION
ultrasoundon tissuesof the centralnervoussystem
and to our presentstateof knowledge
regarding
the
HIS paperconsists
of a reviewof theprincipalphysical
mechanism
involvedin theproduction
of these
results of research which have contributed to our
Air
presentlevel of understanding
of certain effectsof Unit of the Aero MedicalLaboratory,Wright-Patterson
ForceBase,ContractAF33(038)-20922.
* The researchdescribedin this paperis the resultof programs
supported
by the Biophysics
Branchof the Officeof Naval Re-
• Thispaperwaspresented
at theSymposium
onUltrasound
in
Biology
andMedicine
sponsored
bytheUltrasonic
Laboratory
of
search,ContractNonr-336(00),NR 1194)75and the Bio-acoustic the University
of Illinois,Urbana,Illinois,May 25 to 29, 1952.
2
w.J.
O•
FRY
sis is presentimmediatelyafter the irradiation and is
permanent.Experimentshave beenperformedon frogs
with the spinal cord exposedby laminectomyand on
intact animals.In the latter the soundpassedthrough
theoverlyingskin,muscleandbone.Physiologica
! salt
solutionis usedas the couplingmediumbetweenthe
-•
0•2
transducer
and the animal.
The results are the same
whetherthe frog is initially at roomtemperatureor at
IøC whenirradiated.The biologiceffectsof ultrasound
and the underlyingmechanismsappear to be the same
whetherthe frogsare subjectedto 1 or 13 atmospheres
1.0
2.0
;•.0
4.0
5.0
6.0
pressure
at the time of radiation.The quantitativereDRIVING CIRYSTAL VOLTAGE (KILOVOLTS)
lation betweenacousticpressureamplitudeand time of
Fro. 1. Relationsbetweendrivingcrystalvoltage,whichis pro- irradiationfor paralysis
ispresented
in Fig. 1, for a hyportional to acousticpressureamplitude,and reciprocalof the
"minimumtime for paralysis"for frogscooledto IøC and under drostatic pressureof one atmosphere.We define a
hydrostaticpressures
of oneand thirteenatmospheres.
quantity, "the minimum time for paralysis,"as the
minimum period of irradiation which will result in
effects.
'-4 The extensiveEuropeanwork•,6on the action paralysisof all frogssubjectedto the radiation.As can
of ultrasound on tissue will not be discussed since the
be seenfrom the grapha straightline relationshipexists
effectsconsideredhere appear to be limited to sound betweenthe reciprocalof this time and the driving
levelsin excessof thoseusedby mostEuropeaninvesti- crystalvoltagewhich is proportionalto the acoustic
gators. A similar statement applies to the research pressureamplitude.A similar relationbetweendriving
reportedby other investigatorsin this country.? Leh- crystal voltage and reciprocalof paralysistime is obmann's research on the mechanism of action of ultratained for frogsundera hydrostaticpressureof 13 atsound on tissue,s at sound levels used in therapy, mospheres,
as can be seenfrom Fig. 1.
demonstrates
that the temperaturefactor is of primary
It is possibleto obtain summationof successive
importance.
subparalyticexposures
to produceparalysis.The time
It is convenientto subdividethe subjectmatter of courseof recoveryof the spinalcordof a frog from the
thispaperintotwocatagories:
(1) changes
in structure effectsof a subparalyticexposureis indicatedin Fig. 2.
and functionresultingfrom the actionof ultrasoundon Frogsare exposedto a 5.4-seconddoseof radiation at
theorganism,
and(2) thephysicalmechanisms
involved an acousticpressureamplitudewhichalonewouldproin the productionof thesechanges.
duce paralysisin 7.8 seconds.At various times later
thesefrogsare subjectedto a secondperiodof radiation
H. PHYSIOLOGICAL
AND STRUCTURAL
CHANGES
at the samepressureamplitude.The minimum duration
The frog, Rana piplens,has servedas a convenient of the secondexposureto produceparalysisis deterbiologicaltest objectfor a numberof the investigations mined.The difference
in the time intervalfor paralysis
on the effects of ultrasound on nerve tissue. When the
for a singleexposure,
andthe durationrequiredof a later
lumbarenlargement
of a frog spinalcordis irradiated exposureto produceparalysisis shownplotted as a
with soundat a frequencyof one megacycleand at a functionof the time interval betweenexposures.
The
suitable•pressureamplitude,paralysisof the hind legs data presentedin the figuredo not suggesta simple
occurs.The durationof irradiationto produceparalysis monotonicrecoveryprocessfollowingexposure.Howmust be greater than a minimum value which is de- ever, the informationobtainedis insufficientto permit
Pendent
ontheacoustic
pressure
amplitude.
Theparaly- descriptionof the recoveryprocessin any detail.
In additionto the irreversiblechangesproducedby
I Fry, Wulff, Tucker, and Fry, J. Acoust. Soc. Am. 22, 867
(1950).
ultrasoundin the centralnervoussystemof frogswhich
a Fry• Tuckers. Fry, and Wulff, J. Acoust. $oc. Am. 23, 364
result in paralysisand anesthesia,we have obtained
0950.
of reversible
changes
asfollows(unpublished
a Wulff, Fry, Tucker, Fry, and Melton, Proc. Soc.Exptl. Biol. indications
Med. ?6, 361 (1951).
data): One branch of the sciaticnerve, the tibial, is
4Wall, Fry, Stephens,Tucker, and Lettvin, Science114, 686
excitedelectrically
andthe reflexdischarge
throughthe
(19Sl).
• See,for example,the proceedings
Of the Erlangenand Rome spinalcord is observedelectricallyon the peroneal
conferenceson Ultrasoundfor a generalview of the field to 1949- branchof the sciatic.The cordis then subjected
to a
1950. Der Ultraschallin der Medlzin (S. Hirzel Verlag, Zurich,
1949). Supplements
to volumeVII, Ser. IX of N'uovocimento, pulseof acousticradiation with a pressureamplitude
Rome (1950).
abovethe thresholdvalue for paralysis.The reflexdis6H. Heyck, Schweiz.reed.Woch.82, 97 (1952).
by a pulsewhose
?Anderson, Wakim, Herrick, Bennett, and Krusen, Arch. chargecan be completelysuppressed
durationis lessthan that requiredfor paralysis.When
Phys.Med. 32, 71 (1951).
sj. F. K. Lehmann,
J. Acoust.Soc.Am. 25, 17 (1953).
suchis the case,essentially
completerecoveryensues.
•[An amplitudeabovea thresholdvalue,whichis somewhat
choiceof the
dependenton the temperatureof the animaland the hydrostatic It appearsat presentthat by appropriate
pulselengthand the time interval betweenirradiations
pressureof the environment.
ACTION
OF
ULTRASOUND
ON
NERVE
TISSUE
3
this sequence
of eventscan be repeatedindefinitelyor dinted. The bone was removedbecauseof its high
can be designedto result in permanentsuppression,absorption
for ultrasoundat the frequencyused.
i.e., the frogis paralyzed,after any roughlyprescribed The transducerused in irradiating cats and rats
produces
a beamwhichfocuses
at a distanceof 6.4 cm
numberof repetitions.
In contrast to the effectsjust describedisolated from the transducerface.The intensityis down to 0.7
peripheralnerves(frogsciaticand crayfishlegnerves) of the peak value in the radial direction1.3 mm from
are insensitive to sound as measured in terms of thresthe beam axis. The amplitudein the directionof the
holdto electricalstimulationand the shapeand sizeof beamaxisdoesnot changerapidly.The duration,presthe actionpotential.This statementis madefor sound sureamplitude,and positionof the beamof acoustic
at pressure
amplitudesin the rangeusedat presentto radiationare accuratelycontrolled.The shapeof the
effectthechanges
in the centralnervoussystem.Evenex- lesionproduced
by the beamfrom thistransducer
is in
posuresseveralordersof magnitudegreaterthan those the form of a long narrowcylinder.A multiple beam
usedto producemajor changesin the centralnervous focusingtransducernowunderconstructionwill enable
systemproduceonlyminorchanges
in peripheralnerve, us to producelesionssmall in all three dimensions.As
whichare readilyexplainedby the slightheatingthat an outgrowthof the neuroanatomicalstudieswe are
OCCURS.
nowdevelopinga multiplebeaminstrumentfor neuroThe resultsof the histological
studiesof ultrasonically surgicaltest.
irradiatedtissueof the centralnervoussystemof cats,
IIL PHYSICAL
MECHANISMS
rats,andfrogsaredescribed
in detailin anotherpaper.'
Forthepurpose
of a general
reviewandasa background
A. Temperature
for the discussion
of the physicalmechanism
contained
Temperature
changes
whichoccurwhenultrasound
is
hereinpertinentresultsare briefly describedin this
propagated
through
tissue
may
play
a
role
in
producing
paper.Fromthehistological
workan orderof susceptaeffectsin the foilowingways:(1) The temperability to changeby the acousticradiationhas been biologic
establishedfor the varioustissuecomponentspresent ture of the tissue exceeds some value above which
existat interfaces
in the centralnervoussystem.The mostsensitiveele- damageoccurs,(2) hightemperatures
mentsare the large neuronsin the spinalcord. It is in the tissuewhichcouldnot be detectedby a thermopossibleto choosethe dosageof radiation so that coupleas smallas say 0.003in. in diameter,(3) the
the largeneuronsin the irradiatedregionare affected, time rate of changeof temperatureis too great, (4)
but the smallneurons,glia cells,bloodvessels
and nerve temperature
changes
associated
with cavitationare refibersare left intact. As a specificexample,whenthe sponsible,
(5) heatingat gasnuclei.
dosage
is adjustedsothat onlythelargemotorneurons
(1) Fiveindependent
arguments
arepresented
against
of the lumbar•nlargement
of the frogspinalcordare
the
possibility
that
the
temperature
of
the
tissue
exdamagedparalysisof the hindlegsresults.This occurs
ceedsa criticalvalue abovewhichdamageoccurs.
for irradiationtimescloseto the minimumrequiredfor
(a) Experiments
• on cooledfrogs show that the ultrasound
paralysis.
Heavier doses of radiation result in destruction of all
nervecells.Gila cellsand supportingelementsare next
produces
its effectson nervecellswhenthe temperature
levelin
thecordislessthan20øC.Figure3(a) showsa graphof the tempera-
turechangewhichtakesplacein a frogspinalcordas measured
by a 0.003-in.diameterthermocouple,
whenthe lumbarenlargeexposure
of ultravessels
aredilatedbut not brokenat thehighestacoustic mentof the frogis subjectedto a 4.3-second
soundat a levelsufficientto produceparalysiswith twoexposures
pressures,
about 15 atmospheres,
usedin the experi- 4 minutesapart.A singleexposure
of sufficient
durationto cause
affected. Nerve fibers remain intact
and the blood
mentson frogs.In a smallpercentage
of the catswhich paralysis
yieldsthe temperature
change
indicated
by Fig. 3(b).
have been irradiated there has been some blood vessel
damage,but this may be associated
with the high
acoustic
pressures,
about30 atmospheres,
usedin many
of the experimentson cats up to the presenttime.
It shouldalsobe noted that the changesproducedin
the tissueby the ultrasoundbegin to manifestthemselveshistologically
from one to two houRS
after irradiation.The primaryeffectisnot oneof grossdisruption
8O
so
of cellular or nuclear membranes.
Ultrasounddoseswhichproduceparalysisin frogsdo
nogross
damageto theoverlyingskin,mugdeandbone.
All experiments
oncatsandratshaveinvolvedsurgical
removalof the bonesoverlyingthe areasto be irra-
paralyticdoseof ultra.sound.
The experimentally
determined
e Wall, Tucker, Fry, and Mosberg(submittedfor publication).
dose(7.8 seconds)
to yield the valueplottedon the vertical scale.
FIG. 2. Graphicalindicationof the time courseof recoveryof
the nerve tissueof the lumbar enlargementof frog after a subminimumduration requiredof a seconddoseof radiation to
•rroduce
paralysis,
at varioustimesafter the initial periodof
raAiation,
is-subtracted
fromthe durationrequiredfor a shugle
4
W.
20
J.
FRY
cellsor cellsof either shapeof smallerdiameter.We
assumethat there is one absorbinginterfaceper cell.
Let the averagetemperatureof the tissuediffer from
INTACT
PRE-COOLED
FRO•
the averageinterfacetemperatureby the amountAT.
FIO. 3. Temperature If the heat conductivityof the materialat the interface
changesin a frog spinal is of the sameorderas the averagevalue for the tissue,
cord (lumbar enlargement) producedby ul~ or if the interface is of zero thickness,the following
t
2
5
4
trasonnd. (a) Tempera- relationfor the temperaturedifferenceat equilibriumis
OFF
OFF
i (ULTRASOUND
0•1
4.3
•
o
OFF•o
SEt N
E•ED
TIME-
MI•TES
ture changes accom- obtained:
panying two 4.3-second
exposuresseparated by
OFF
3o
a
4-minute
interval.
Paralysis is produced
after the secondexpo-
sure. (b) Temperature
changes
accompanying
a
single exposureof sufficient duration to produceparalysis.
4
8
ELA•EO
•
14
TIME- SECONDS
A maximum of 30øC is attained. An intact frog immemedin a
warmwater bath to hold the cord temperatureat 30øCdoesnot
exhibit impairmentof motorfunctionsafter onehalf-hour.
AT = MoL/KA,
(1)
where• is the averageintensityabsorptioncoefficient
per unit path lengthof the tissue,i.e., the usualmeasuredvalue,I0 is the soundintensity,L is the celldiameter, A is the total area of the interfacesper unit
volume,and K is the coefficient
of heat conductivity.
At a soundintensityof 50 watts/cm2 and a value of
• of 0.4 per cm and usinga value for the heat conductivity equalto that of water, the calculatedvalue of the
temperaturedifference
islessthan0.001øC.Refinements
of thisargumentto include,for example,suchsituations
asinterfaces
of finitethickness
of greatlydifferentheat
conductivitycharacteristicsfrom the averagefor the
tissue,do not changethe generalconclusionthat localized heatingat interfacescannotbe importantin the
(b) Summation
• of the biological
effectsin motorneurons
producedby soundpulses,separatedby periodsof time longcom- mechanism.
paredto the intervalrequiredfor the tissueto return to its initial
(3) The possibilitythat subjectingthe tissueto a
temperatureprovesthat paralysis(in the caseof irradiation of
time rate of changeof temperaturegreater than a
the lumbarenlargement
of a frogspinalcord)is not dependent
on
achievingany particulartemperaturelevel. Comparethe two certain minimum value is sufficientto produce the
graphsin Fig. 3. The temperaturelevelsattainedare completely effectsis incompatiblewith the quantitativerelations
different in the two cases.
of Fig. 1. Neglecting conduction,which is justified
(c) On the basisof the experimentallydeterminedrelations during the initial part of the irradiation period, these
betweenminimumparalysistimeandacoustic
pressure
amplitude
•
relationsyield the followingfunctionalform relating
(Fig. 1) it is readilyseenthat theabsorption
of a constantamount
of acousticenergyby the tissueis not requiredto producethe paralysistime, t•,, to time rate of changeof temperaeffect.
ture, dT/dt:
(d) Thermocoagulation
studies
•a-nonthecerebralcortexby other
(2)
investigators
haveshownthat, whenthe largecellsare destroyed
by heating,the smallcellsin the tissueare alsodestroyed.I-Iow4 where m and b are constants.
ever,in our studieswith ultrasoundit is evidentthat the largecells
(4) The fourthpossible
mannerin whichtemperature
are particularly sensitiveto the a•ousticradiatlon2.•4
might producebiologicaleffectsis in association
with
(e) Preliminarystudiesat $00 kc have been made at a single
eavitation,
defined
here
to
include
both
the
process
of
value of the acousticpressureamplitude.The minimumexposure
time required to produceparalysisof the hind legs of frogs by cavity formation and collapsein the tissue(initiated at
irradiation over the lumbar region of the spinal cord has been a point of low tensile strength) and the growth and
determined.In order to obtain equal temperaturelevelsin the collapseof a gas nucleusin the tissueunder alternate
cord at $00 kc and 1 me in equal exposuretimes the ratio of the
two intensitiesshouldbe in the ratio of absorptioncoefficients.
Such a ratio of intensitiesis not required for paralysis at the two
frequencies.
tensionand compressionforces.It has been shownthat
the biologicaleffectsof ultrasound,on the tissueof the
central nervoussystemare the samewhether the exposure is made under a hydrostatic pressureof one
(2) It has been shown on the basis of a theoretical
atmosphereor under a pressuresufficientlyhigh to
analysispresentedin oneof our publishedpapers
2 that
diminate tensionforcesin the biologicalmaterialh
the existenceof high temperaturesat interfacesin the during acousticpropagation? This eliminatespossible
cordisunlikely.Theargumentcanbebrieflysummarized temperaturechangesassociatedwith cavitation as imas follows. Assume that all sound absorbed in the tissue
is absorbed at interfaces. Consider a volume of material
portant in the mechanism,since in the absenceof
tensionforcescavitationdoesnot take place.It is also
consistingof cylindricalcellsof diameter 10 microns.
noted that the quantitativerelationbetweenparalysis
The temperaturechanges
wouIdbe smallerfor spherical
time and acousticpressureamplitudeis of the same
•oW. S. McCulloch(privatecommunication).
form at the differentpressures.
n Dusserde Barerme,Salenee77, 546 0933).
(5) The possibilityof high temperaturesproduced
a Dusser de Barenne and H. M. Zimmerman, 'Arch. Neurol.
during an acousticdisturbanceat or near the surfaces
Psyckiat.Chicago,33, 123 (1935).
ACTION
OF
ULTRASOUND
of small gasnuclei,in the absenceof tensionforces,
mustalsobe considered
in discussing
the mechanism
of
the biological
effectsdescribed
in this paper.A mechanism basedon the existenceof such temperature
changes
is unlikelyfor the followingreasons.
ON
NERVE
TISSUE
5
in bubbleradiuswerequirea numerical
estimatefor the tempera-
turechange
at thesurface
of a gasnucleus
witha diameter
equal
to onehalfof a micron.The followingrelation,derivedby Rosenberg,•s will be used to obtain suchan estimate.It is assumed
that the gas filling the nucleussatisfiesthe conditionsof a
perfect gas and that the diameterof the fiucleusis restricted
to valuessmallcomparedto the wavelength
of the acousticdis(a) Intracelhlargasnucleiof diameters
equalto or greaterthan turbance.For a steadystatecondition,whichneedonly be conaboutone-halfof a micronwouldbe detectablemicroscopically.sidered
herebecause
the timesrequiredto produce
the biological
However, there is no evidencefor the existenceof such nuclei. effectsdescribed
in thispaperareverylongcompared
to a period
We assumethen that if gasnucleiare presentthey are lessthan of the acousticdisturbance,Rosenbergobtainsthe following
onehalf of a micronin diameter.Sincethe maximumtemperature resultfor the difference
betweenthe temperature,Tin,at the surchangeoccurs,in the imbeddingmaterial, at the surfaceof the faceof thebubbleandthe temperature,
To,whichthe imbedding
bubble,and sincethe temperatureriseincreases
with an increase mediumapproaches
as onemovesaway from the bubblesurface.
[-(l+/)R82-}-IJ
sinh(lq-j)RS•
,'[bt• i,•t
(To--To)
={(lq-j)[(K•/K2)RSt
cosh(lq-j)R•q-R•2
sinh(1-I-j)R•]-{-(1
--K•/K•)
sinh(1-l-j)R•
fa•
where
at=(•oa•/2)•, a•=oC•/Ki,
(3)
tensionforcesexistin the materialduringacoustic
ba=-l/Kx.
propagation.It is the observationthat cavitation is
Subscript
1 refersto thematerialwithinthebubbleandsubscript
2
refers to the surroundingmaterial. The acousticdisturbancein
absentin theexperiments
performed
undertheincreased
theregionof thebubbleis represented
by Poei'*t,wherePois the pressureand therefore could not enter into the mecha-
pressureamplitude.The symbolsin the aboveformulaare defined
as follows: R, radius of bubble; Ki, coefficientof thermal conductivity; o6 density; C•, heat capacity per unit mass.
If the inequalityR$•_<1/3 is satisfiedrelation(3) can bewritten
in the approximateform
f(1/3)(l+J)•(K•/K2)(atR)•]
btp•,o•
lq-(1--•-j•-• f• 0e.
(4)
nismin anyway.Thesecond
is the experimental
observationthat notearing,vacuoleformation,
or grossdisruptionwhichwouldbeexpected
to accompany
cavitation wasseenin tissueirradiatedat oneatmosphere
pressure
and fixed immediatelyafter exposure.
The
thirdfollowsfromstudies
of the pathology
of decompression
sickness.
Thesehaveshownthat in the central
The absolutevalue of T,-To for an air bubbleof 1/2 micronin nervoussystemnecrosis
is more commonin the white
diameterin water and subjectedto an acousticdisturbanceat a
matter
than
in
the
gray
matter.TMThis is in contrast
frequencyof one megacycleand at a pressureamplitudeof 15
to the action of ultrasound. The cell bodies are much
atmospheres
is about 0.3øC. This computationthus indicates
that the effect under discussioncannot be important in the more susceptibleto the action of the soundthan the
mechanism of the effects of ultrasound
herein.
on nerve tissue described
fibers.
IV. CONCLUDING
NOTE
(b) No evidenceof the growth of gas nucleiis seenunder the
microscopein
nervetissueirradiatedat a hydrostaticpressure
ofone
It isfeltthatwearestillin theearlystages
ofrealizing
atmosphereand fixedwithin two minutesafter exposure.
Vacuole
formation(andprobablytearingof finefibers)wouldbe expected the potential/tiesof high levelultrasoundas a tool for
if suchgasnucleiexistandcouldgrowundertensionforcesof the quantitative researchon the structureand functionof
orderof 15 atmospheres.
livingorganisms.
It isalreadyestablished
asa powerful
(c) It wouldbe necessary
to assumein additionto the existence
method
in
investigations
of
the
organization
andactivof gasnuclei,eitherthat the populationof suchgasnucleiper unit
systems.
Sincethe primary
volumeis greaterin largenervecell bodiesthan in smalland is ity of centralnervous
especially
low in axons,or that cellsof differentsizesand axons actionis apparentlynot oneof gross
disruptionof, for
containconstituentswhich vary tremendously
in their suscep- example,
cellularor nuclearmembranes,
it may also
tibility to damageby temperaturechange.Sucha possibilityas
develop
into
a
method
of
studying
intracellular
organithe latter, concerningthe temperature sensitivity of cellular
constituents,
seemshard to reconcilewith the experimental
evi- zation.The relativelyrapid time courseof resulting
dencereferredto aboveon the sensitivityto heat of the cellsof the physiological
changes
makeit especiallyattractivein
cerebral cortex.
B. Cavitation
this regard.It is anticipatedthat a studyof the effects
as a functionof frequencywill provideessentialinformationfor the construction
of a theoryof the fundamental mechanism.
The possiblerole of cavitationwhich one might
investigate,
after the temperaturefactorin a studyof
ACKNOWLEDGMENT
the physicalmechanism
by whichultrasound
produces
The followinginvestigators
contributedto the rethechanges
in thecentralnervoussystemunderreview
here has already receivedsome considerationin the searchreviewedin this paper: D. Tucker, F. J. Fry,
aboveanalysisof the temperaturefactor.Threefurther P. D. Wall, and V. J. Wulff.
commentsmight be added,the first is a direct conse•sM.D. Rosenberg,
Tech.Memo.No. 25, Acoustics
Research
quenceof the experimentalresultsobtainedunder a Laboratory,
Harvard University.
hydrostaticpressure
sufficiently
highto insurethat no
• H. R. Catchpole
andI. C-ersh,
Physiol.Rev.27,360(1947).