The history of the gamma knife PDF
Preview The history of the gamma knife
Advisory Editors Stephen G. Waxman BridgetMarieFlahertyProfessorofNeurology Neurobiology,andPharmacology; Director,CenterforNeuroscience& Regeneration/NeurorehabilitationResearch YaleUniversitySchoolofMedicine NewHaven,Connecticut USA Donald G. Stein AsaG.CandlerProfessor DepartmentofEmergencyMedicine EmoryUniversity Atlanta,Georgia USA Dick F. Swaab ProfessorofNeurobiology MedicalFaculty,UniversityofAmsterdam; LeaderResearchteamNeuropsychiatricDisorders NetherlandsInstituteforNeuroscience Amsterdam TheNetherlands Howard L. Fields ProfessorofNeurology EndowedChairinPharmacologyofAddiction Director,WheelerCenterfortheNeurobiologyofAddiction UniversityofCalifornia SanFrancisco,California USA Elsevier Radarweg29,POBox211,1000AEAmsterdam,Netherlands TheBoulevard,LangfordLane,Kidlington,OxfordOX51GB,UK 225WymanStreet,Waltham,MA02451,USA Firstedition2014 Copyright#2014ElsevierB.V.Allrightsreserved Nopartofthispublicationmaybereproducedortransmittedinanyformorbyanymeans, electronicormechanical,includingphotocopying,recording,oranyinformationstorageand retrievalsystem,withoutpermissioninwritingfromthepublisher.Detailsonhowtoseek permission,furtherinformationaboutthePublisher’spermissionspoliciesandour arrangementswithorganizationssuchastheCopyrightClearanceCenterandtheCopyright LicensingAgency,canbefoundatourwebsite:www.elsevier.com/permissions. Thisbookandtheindividualcontributionscontainedinitareprotectedundercopyrightbythe Publisher(otherthanasmaybenotedherein). Notices Knowledgeandbestpracticeinthisfieldareconstantlychanging.Asnewresearchand experiencebroadenourunderstanding,changesinresearchmethods,professionalpractices,or medicaltreatmentmaybecomenecessary. Practitionersandresearchersmustalwaysrelyontheirownexperienceandknowledgein evaluatingandusinganyinformation,methods,compounds,orexperimentsdescribedherein. Inusingsuchinformationormethodstheyshouldbemindfuloftheirownsafetyandthesafety ofothers,includingpartiesforwhomtheyhaveaprofessionalresponsibility. Tothefullestextentofthelaw,neitherthePublishernortheauthors,contributors,oreditors, assumeanyliabilityforanyinjuryand/ordamagetopersonsorpropertyasamatterofproducts liability,negligenceorotherwise,orfromanyuseoroperationofanymethods,products, instructions,orideascontainedinthematerialherein. ISBN:978-0-444-63520-4 ISSN:0079-6123 ForinformationonallElsevierpublications visitourwebsiteatstore.elsevier.com Preface No invention or discovery is ever produced in a vacuum. First, there must be a perceivedunfulfilledneed.Thiswillusuallybefollowedbyattemptstosatisfythat needwhichmaynotalwaysbesuccessful.Themostfamiliarexampleofpersistent lackofsuccessisthealchemists’failuretotransmutebasemetalsintogold.Oneof thesequencesofthiskindappliedtomedicineistheintroductionofanewtreatment concept.Fromconcepttofruitionintheformofausablenewmethodispainstaking andtimeconsuming.Thispartoftheprocessmayinvolveusefulbutsuboptimalnew ideasormethodswhichrequirerepeatedadaptation.Chancealsoplaysapart.More- over,atreatmentperceivedimperfectlyinitiallymaybeimprovedbytotallydifferent personsfromthosewhofirstinitiatedthenewnotionsandthehonormaywellgoto thediscovererofthesuccessfuladaptedmethodratherthantotheoriginalcreative thinkerwhoinitiatedtheinvestigationswhichendedinsuccess.Furthermore,along theway,aconservativeprofession,concernedforboththepatientsunderitscareand thestandardoflivingofitsmembers,maywellopposeanythingnewbecauseunpro- ven novelty may threaten both patients’ safety and practitioners’ domestic luxury. This sequence of partial success, acceptance, and resistance to change and final successofatrulyeffectivenewmethodshouldbeseenascharacteristicofmedical advanceswhich,likeitornot,aresoughtandimplementedbyhumanbeingswithall our talents, virtues, and weaknesses. No better example of the sequences involved can be found than the series of events which led to the discovery of smallpox vaccination. Lady Mary Wortley Montagu (1689–1762), daughter of the Earl of Kingston upon Hull, was a woman of beauty, wit, and independence of spirit unusual at her time.Herfatherpressedhertomarryamanofdistinctionandpropertywiththepos- itivelyDickensiancognomenofClotworthySkeffington,anIrish noblemanwhom shedidnotfancy.Sosheelopedin1712andmarriedEdwardWortleyMontaguin Salisbury.In1715,shecontractedsmallpoxwhichshesurvivedbutwithsomescar- ring.Herbrotherdiedfromthedisease.ShehadpreviouslybeenaCourtfavoritebut hersatiricalwritingsaboutthePrincessofWales,writtenwhileshewassickbarred herfromCourt.ShethusjoinedherhusbandwhohadbeenappointedBritishambas- sadortoTurkey.Theresheencountered thepractice ofvariolationwhereby matter fromaninfectedpersonwasinjectedintotheveinofsomeonetoinduceamildattack ofthe disease,hopefullywith minimal scarring and lifelong immunity.The proce- durewasnotwithoutriskbecausesomeinoculatedindividualscouldsufferasevere formofsmallpoxwhichcouldprovelethal.Nonetheless,itsacceptancebytheupper reachesofsocietyledtoitsincreasinguse.Oneofthosewhohadsurvivedvariolation but was never as fit afterward as he had been before was Edward Jenner (1749–1823). While trained by the best in London, he was at heart a country boy andreturnedtopracticeinBerkeleyinGloucestershirewherehismuseumisfound tothisday.Asacountrydoctor,hehadheardofthepracticeofinoculatingmilkmaids withabovineformofthediseaseconferringimmunity.Duetotherarityofcowpox, v vi Preface itwasnoteasytoperformroutineinoculations,butthosewhowereinoculatednever sufferedsmallpox,includingJenner’slittleson.Thesuccessoftheprocedureneeds nofurthercomment.Nonetheless,themethodwascriticizedinthemedicalprofes- sion,notleastbythosewhoreceivedsubstantialfeesforperformingvariolationso thatitwasatimebeforethetreatmentbecameuniversallyaccepted.Thissortofre- actionfollowingtheintroductionofanewmethodinsurgeryisnotunfamiliar.One couldconsiderSemmelweisandhandwashingandListerandantisepsis,neitherof whomreceivedrapturousapplausefortheircontributions.Duringthepassageofthis book,itwillbeseenthattheprocesseswhichendedupwiththediscoveryofsmall- poxvaccinationwouldalsoaffecttheinventionofradiosurgeryandtheperfectionof instruments for its satisfactory performance. This will be particularly illustrated in Chapter 11. In the 1930s, the treatments of inaccessible cancers and neurosurgical diseases were frustrating and inefficient. However, this was a time when understanding of atomicstructureandspontaneousbreakdownofunstableradionuclideswasexpand- ingrapidly.Thefrustrationwiththepoorresultsofexistingtreatmentswasthespur todevelopnewmethods.Thefirsttoattempttheuseofatomicparticlesinradiation treatmentsweretheLawrencebrothersinBerkeley,California,spurredonbynoless a person than Harvey Cushing, who contributed to John Lawrence’s training and clearlyhadagreatrespectforhim.TheelderbrotherErnestinventedthecyclotron to accelerate subatomic particles. The younger brother, John Lawrence, pioneered theuseoftheseparticlesinthetreatmentofdiseaseusingbothradioactivenuclides andlaterwell-definednarrowparticlebeams.Itshouldhoweverbementionedthat theBerkeleygroup,whileperformingextraordinarycreativework,wereapplyinga medical functiontoa machinedesigned for a different purpose. InSweden,agroupofscientistsdevelopedandexpandedtheBerkeleytechnique tothepointwheretheclinicaltreatmentofavarietyofconditionsbecamepossible. TheSwedishgroupwereincontactwiththeBerkeleygroupandexpresstheirindebt- edness ina number oftheir papers. However,while the particle beam method was elegant, it was also complex and impractical outside of a laboratory containing a cyclotronwhichcouldgeneratetheparticles.Thisledtothedesignandproduction of the only machine in the world which was specifically constructed to perform radiosurgery, the gamma unit subsequently to becalled the Gamma Knife. The purpose of this book is to trace the history of the ideas and attempts at ra- diosurgery treatments from the first hesitant steps in California to the production of the most modern radiosurgery machine the Gamma Knife Perfexion. The part played by chance is well illustrated in the above account of vaccination. Mary Montaguewasagirlofspiritwhoopposedherfather,marriedthemanofherchoice, sustained smallpox, wrote the wrong thing, and had to travel to Turkey where she came into contact with variolation which she was in a social position to introduce intoLondonsociety.JennerwasacountryladatheartbutduringhistimeinLondon suffereduncomfortableeffectsfollowingvariolationandwasasacountrydoctorina position to be aware of cowpox and the smallpox resistance of milkmaids. The Lawrences were both talented but by chance John came into contact with Harvey Preface vii Cushing who supported the activities of him and his brother and World War IIin- evitably did no harm to funding the laboratory where the work was carried out. In Sweden,Leksellstartedamedicalcareerbychanceandwaspossessedofamindset whichenabledhimtodesignusefulinstruments,perhapsinpartbecauseasachild he’dhadthechancetoworkundersupervisioninthemachineshopofthefactoryhis father owned. He also had access to a supremely talented physicist B€orje Larsson 20 years his junior without whom the gamma unit would not have been possible. OneconsequenceofLeksell’ssocialpositionwashisnetofpersonalrelationships, whichincludedBoAx:sonJohnsononeoftheownersanddirectorsofthewealthy AxelJohnson Group which during the relevant period owned the Studsvik nuclear power plant, the Motala Verkstad engineering workshop, and the Avesta Jernverk aworkshopwhich alsospecialized inmetal work.TheJohnsonGroupthus owned all the industrial facilities which would be required to manufacture a radiosurgery machine. While there remains evidence of a detailed and comprehensive interest on the part of the Swedish state to ensure the new machine’s specifications and patient safety were acceptable, there was no financial assistance from the state. The contribution from national coffers was limited to grants for the research work inUppsaladuringthe1950sand1960swhichwouldformthebasisforproceeding with a commercially produced machine. Thus, Leksell’s relationship with senior levels of the Axel Johnson concern was a happy chance for the development of the originalgamma unit, leading tothe entirelyprivatefinancing ofthe machine’s development and manufacture arising out of respect Bo Ax:son Johnson had for Leksell’swork. In conclusion, it should be remembered that the nature of scientific advance meansthatadaywillcomewhentheGammaKnifePerfexionisnotthebestinstru- mentforitspurpose.However,thatdayhasnotcomeyetandthereisnosignthatit will come soon. Acknowledgments Theauthorwouldliketothankthefollowingpeoplewithoutwhoseinvaluableadvice andassistancethisbookcouldnothavebeenwritten.First,Dr.DanLeksell,theson oftheinventoroftheGammaKnife,hasbeenfreewithinformationabouttheearly daysofradiosurgeryandhasgivenaccesstorelevantpaperswhichwouldotherwise have been inaccessible. He has also been an invaluable adviser on textual purity. Next,thereisDr.BertSarbyaphysicistwhowasintimatelyinvolvedinthedevel- opmentoftheearlygammaunitandhasgivenfreelyofhistimeandhisliteratureto ensuretheaccuracyofthetext.HansSundquist,theengineerwhoturnedtheideasof designersintopracticalmachines,hasalsolistenedtotheauthor’squestionsandan- swered promptly and concisely whenever approached. I should like also to extend my gratitude to Dr. Rich Levy from Berkeley who was generous with his time andinformationaboutcyclotronradiosurgery.Finally,tomyoldfriendJu¨rgenArndt anotherphysicistwithwhomIhaveroamedtheworldteachingthepracticeofradio- surgery from Mexico to Tokyo via Beijing. He has repeatedly advised on the evolving text. Alloftheabovepersonshavenotonlyadvisedonthisprojectbutalsohaveread throughthetexttoensuretheirinformationiscorrectlyrelayed.Itwouldberemissof meifIdidnotalsothankProfessorErikOlofBacklund,mychiefinBergenandmy mentorinthemysteriesofradiosurgery.Hehasbeenakindandconsistentlyenthu- siastic support over the years and has also been helpful in supplying valuable and otherwise unavailable details fromthe early days. Finally, I should like to thank my wife, Gao Nan Ping or Annie Gao, as she is knowntohermanyfriendsintheradiosurgerymilieu.Thewifeofanymanwriting abookhastoputupwiththeabsences,trips,andchangingmoodsoftheauthorashe pursueshis aims. Without Annie this bookcould nothave been written. xv CHAPTER 1 Background knowledge in the early days Abstract Thepurposeofthischapteristooutlinethemedicalfacilitiesthatwereavailabletotheinven- torsofradiosurgeryatthetimewhenthetechniquewasbeingdeveloped.Thisisachievedby describinginbriefthetimelineofdiscoveriesrelevanttoclinicalneurologyandtheinvesti- gationofneurologicaldiseases.Thisprovidesabackgroundunderstandingforthelimitations inherentintheearlydayswheninvestigationsandimaginginparticularwerefairlyprimitive. Italsohelpstoexplainthechoicesthatweremadebythepioneersinthoseearlydays.The limitations of operative procedures and institutions designed to treat neurological diseases arealsomentioned. Keywords clinicalneurology,radiology,contraststudies,operatingtheaters,neurologicalhospitals 1 INTRODUCTION RadiosurgerywasfirstdefinedbyLarsLeksellinthefollowingterms:“Stereotactic radiosurgeryisatechniqueforthenon-invasivedestructionofintracranialtissuesor lesionsthatmaybeinaccessibletoorunsuitableforopensurgery”(Leksell,1983). Asstatedinthissection,nohumanactivityoccursinavacuumincludingthedevel- opmentofmedicaltechnology.Radiosurgerywasdevelopedoutoftheperceptions and efforts of a small group ofmen who passionately believed that such a method was urgently needed in the battle against a large number of contemporaneously untreatable diseases. The possibility of developing radiosurgery was a spin-off of thedevelopingfieldofnuclearphysics,whichwassuchacharacteristicdevelopment ofthefirsthalfofthetwentiethcentury.Whatwasrequiredwouldnotbeclearatthe start,butwouldbecomeso.Therewerefiveessentialelements.Thefirstchaptersof thisbookconcern thejourney towardunderstandingandeventually theimplemen- tationof these elements;and itwas a long journey: 1 ProgressinBrainResearch,Volume215,ISSN0079-6123,http://dx.doi.org/10.1016/B978-0-444-63520-4.00001-6 ©2014ElsevierB.V.Allrightsreserved. 2 CHAPTER 1 Background knowledge in the early days 1. Imagesthatenablethevisualizationofthelesiontobetreatedareanessentialpart ofthe method. 2. Athree-dimensionalreferencesystemcommonforimaging,treatmentplanning, and treatment. 3. Atreatmentplanningsystembymeansofwhichtheirradiationofeachcasecan be optimized. 4. Ameansof producing well-defined narrow beams ofradiationthat selectively and safely deliver the radiation dose under clinical conditions. 5. Adequateradiationprotection. 2 CLINICAL NEUROLOGY Thisbookconcernsneurosurgeryandneuroradiosurgeryandsurgeryofthecentral nervoussystem(CNS).Atthetimewhentheprocessesthatwouldleadtoneurora- diosurgery were beginning—around 1930—neurosurgery’s contribution to patient welfare,whilemorerationalandscientificallybasedthananyatthetimeinitspre- vious history, had relatively little to offer. Certainly, cell theory had permitted the analysisofthecellularcomponentsoftheCNSandtheirarchitectureandinterrela- tionships.Basedonthisnewknowledge,clinicalneurologyhadmadegreatstrides withthedevelopmentoftheexaminationoftheCNSbasedontheunderstandingof howitsdifferentcomponentswereinterconnected(Compston,2009).JohnMadison Taylor had introduced the reflex hammer in 1888 (Lanska, 1989). Gradual under- standing of how to examine the CNS was propounded by Joseph Babinski (1857–1932)in1896(Koehler,2007).ErnstWeber(1795–1878)andHeinrichAdolf Rinne(1819–1868)hadintroducedmeansofdistinguishingbetweenconductiveand neurogenichearinglossalthoughtheprecisedateoftheirtestshasprovedimpossible to determine. These testsrequire tuning forks that had been originally invented by John Shure (ca. 1662–1752) reaching the advanced age for the time of 90 years. He was distinguished enough that parts were written for him by both Ha¨ndel and Purcell (Shaw, 2004). It was applied to neurological testing first in 1903 (Freeman and Okun, 2002). The ophthalmoscope was invented by Helmholtz in 1851(Pearce,2009).Itwasdevelopedanditssourceofilluminationwasimproved oversucceedingdecades.DuringmytimeattheNationalHospitalforNervousDis- eases,QueenSquare,London,Iwastoldthatsuchwasthevaluegiventoophthal- moscopythattherewasatimewhenjuniordoctorsatQueenSquarewererequiredto examinethefundusofpatientssuspectedofraisedintracranialpressure(ICP)every 15min.In1841,FriedrichHofmanninventedtheotoscope(Feldmann,1995,1997). Inthe1930s,theexaminationoftheCNSwasbecomingfairlypreciseandthis precisionwouldimproveoverthedecadestocomeuntilthearrivalofcomputerized imaginginthe1970sand1980s.Untilthen,clinicalexaminationwas themostac- curatemethodforlocalizingpathologicalprocesses.However,notallclinicalsymp- tomsarisefromidentifiablefociofdiseases.Thus,subacutecombineddegeneration of the cord gives a complex picture with some tracts affected more than others. 3 Investigations 3 Again, in multiple sclerosis, with intermittent lesions varying in time and space, a simple localization from clinical information would be difficult. However, this is notthatimportantfortheperformanceofasurgicaltechniqueofwhichradiosurgery isonebecausesurgicalconditionsaresingleandfocalinthevastmajorityofcases. Theadvancesdescribedinthepreviousparagraphsgreatlyincreasedtheaccuracy withwhichaskillfulcliniciancouldlocalizethepositionofapathologicalprocess within the CNS. Even so, the first systematic monograph on clinical neurological localization was published as late as 1921 by a Norwegian, Georg Herman Monrad-Krohn (1884–1964), writing in English (Monrad-Krohn, 1954). In 1945, the moreor less definitive text by Sir Gordon Holmes(1876–1975) was published (McDonald, 2007). 3 INVESTIGATIONS 3.1 ELECTRICAL As far as functional investigations were concerned, electroencephalogram (EEG) became commercial in1935 and electromyography (EMG) arrivedin 1950. 3.2 IMAGING Intermsoffurtherradiologicalinvestigations,thefirstvisualizationoftheCNScame with the use of contrast-enhanced X-ray studies introduced by Cushing’s student Walter Dandy (1886–1946), specifically pneumoencephalography (1918) (Dandy, 1918)andpneumocisternography(1919)(Dandy,1919).Whiletheseexaminations were undoubtedly an improvement, yet to modern eyes, they still look primitive. Then,in1927,camecarotidangiographythatwhileafurtherimprovementwasstill limited and not without risk. Vertebral angiography became routine in the early 1950s. Abrief description ofthe way these methods works follows. Since the first radiosurgeryinformationwaspublishedintheearly1950s,itisnecessarytoseehow thenecessaryimagingforradiosurgerycouldbeachievedatthattime.Ifwebearin mindthatthetechniquewassolelyusedforintracranialtargets,therewerebasically three imaging techniques. 3.2.1 Plain Skull X-Rays PlainskullX-raysexistedbutwereoflittlevalueinshowingtargetssuitableforra- diosurgery.TherightsideofFig.4showsanX-rayoftheskull,takenfromtheside, andindicatesthattheonlyreliablelocationofanintracranialsofttissueistheposi- tion ofthe pituitary gland (see Figure4). Following 1918, it became clear that parts of the brain could be demonstrated usingwhatarecalledcontrastmedia.Thesearefluidsubstances(liquidorgas)that affect the passage of X-rays through the skull. Either they let the rays pass more easily,inwhichcasetheywilldarkenthepartoftheimagewheretheyare,orthey willstopthempassingsoeasily,inwhichcasetheportionoftheimage-containing 4 CHAPTER 1 Background knowledge in the early days mediumwillappearlighter.Themostfrequentlyusedmediuminthiscontextwasair and how it worked requiressomeexplanation. 3.2.2 Brain and CSF Anatomy Itisnecessarytodigressalittleandexplainsomefactsaboutintracranialanatomy. The brain sits tightly enclosed within the skull but it is floating in a bath of fluid called cerebrospinal fluid (CSF). This is created at roughly 0.32ml/min. Figure 1 isadiagramoftheanatomyofthebrainandthefluid-filledspaces(calledventricles) thatitcontains.Figure2illustrateshowtheCSFismadeintheventriclesandflows throughthebrain.Itleavestheventriclesandflowsoverthebrainbetweentwomem- branes, the pia mater and the arachnoid. The pia mater means soft mother and is calledthatbecauseitembracesthebrainasamotherembracesherchild.Thearach- noidissocalledaftersomeimaginativeanatomistslookingthroughthemicroscope consideredthatthemembraneandthespaceunderitlookedlikeaspider’sweb.In Greek mythology, a skillful but arrogant young lady called Arachne challenged Athena,thegoddessofamongotherthingsweaving,toaweavingcontest.Thegirl inevitablylostandwasturnedintotheworld’sfirstspider.Thus,spidersarecalled arachnids and this explains the use of the term arachnoid in the current context. It should be remembered that at any one time, there is about 150ml of CSF in the system and two-thirds ofit isoutside the brain inthe subarachnoid space. 3.2.3 Contrast Studies: CSF Replacement Studies Let us return to imaging. Plane X-rays were of little help, but in 1918, Cushing’s pupil Walter Dandy had discovered that the introduction of air to replace the CSF couldprovidedemonstrationoftheventriclesofthebrainandanydistortionsordis- placements of that system. The air could be introduced either into the spinal canal FIGURE1 Thisdiagramillustratestheshapeoftheventricleswithinthebrain.Therearetwolateral ventriclestothesideofthemidlineineachcerebralhemisphere,andthethirdandfourth ventriclesinthemidlineareconnectedbytheaqueduct.
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