Over the last 13 years -- one, three, 13 years -- I've been part of an exceptional team at InSightec in Israel and partners around the world for taking this idea, this concept, noninvasive surgery, from the research lab to routine clinical use. And this is what I'll tell you about. 13 years -- for some of you, you can empathize with that number. For me, today, on this date, it's like a second bar mitzvah experience.
Zadnjih trinajst let, ena - tri, trinajst let, sem bil del izjemne ekipe izraelskega zdravstvenega podjetja InSightec in partnerjev po vsem svetu, s katerimi smo želeli idejo oz. koncept neinvazivnega kirurškega posega prenesti iz raziskovalnih laboratorijev v klinično prakso. O tem vam bom danes pripovedoval. Trinajst let -- nekateri bi z mano sočustvovali. Jaz pa danes, na ta dan, praznujem nekakšno drugo bar micvo.
(Laughter)
(Smeh)
So this dream is really enabled by the convergence of two known technologies. One is the focused ultrasound, and the other one is the vision-enabled magnetic resonance imaging. So let's first talk about focused ultrasound. And I hold in my hand a tissue-mimicking phantom. It is made out of silicon. It is transparent, made just for you. So you see, it's all intact, completely transparent. I'll take you now to the acoustic lab. You see the phantom within the aquarium. This is a setup I put in a physics lab. On the right-hand side, you see an ultrasonic transducer. So the ultrasonic transducer emits basically an ultrasonic beam that focuses inside the phantom. Okay, when you hear the click, this is when the energy starts to emit and you see a little lesion form inside the phantom. Okay, so everything around it is whole and intact. It's just a lesion formed inside. So think about, this is in your brain. We need to reach a target inside the brain. We can do it without harming any tissue. So this is, I think, the first kosher Hippocratic surgical system.
Te sanje smo uresničili z združitvijo dveh znanih tehnologij. Ena je usmerjen ultrazvok, druga pa magnetna resonanca z vizualnim predstavljanjem. Začnimo z usmerjenim ultrazvokom. V roki držim model, ki prikazuje tkivo, narejen iz silikona. Je prozoren in izdelan prav za vas. Kot vidite, je čist in popolnoma prozoren. Sedaj vas bom popeljal v akustični laboratorij. Tu vidite ta model v akvariju, gre pa za postavitev v fizikalnem laboratoriju. Na desni strani vidite ultrazvočni prevodnik. Ta ultrazvočni prevodnik oddaja ultrazvočni signal, ki se fokusira znotraj silikonskega modela. Ko zaslišite klik, se začne oddajati energija in vidite majhno sled, poškodbo znotraj modela. Vse okrog nje pa je ostalo celo in nedotaknjeno. Poškodba tkiva je nastala le v notranjosti. Zamislite si, da so to vaši možgani in mi moramo doseči točko znotraj njih. To lahko storimo ne da bi poškodovali ostalo tkivo. To je torej po mojem mnenju prvi Hipokratov košer operacijski sistem.
(Laughter)
(Smeh)
Okay, so let's talk a little bit about ultrasound, the force of ultrasound. You know all about imaging, right, ultrasound imaging. And you know also about lithotripsy -- breaking kidney stones. But ultrasound can be shaped to be anything in between, because it's a mechanical force. Basically, it's a force acting on a tissue that it transverses. So you can change the intensity, the frequency, the duration, the pulse shape of the ultrasound to create anything from an airbrush to a hammer. And I am going to show you multiple applications in the medical field that can be enabled just by focusing, physically focusing.
Naj povem nekaj stvari o ultrazvoku, o moči ultrazvoka. Vsi poznate ultrazvočne posnetke, kajne? Poznate tudi litotripsijo, metodo drobljenja ledvičnih kamnov. A ultrazvok lahko predstavlja še marsikaj drugega, saj gre za mehansko silo. V osnovi ta sila vpliva na vlakno, na katerega je usmerjena. Spreminjamo lahko jakost, frekvenco, trajanje, obliko ultrazvočnega signala in tako ustvarimo karkoli, od airbrusha do kladiva. Pokazal vam bom različne možnosti uporabe v medicini, ki jih omogoča zgolj fokusiranje, fizično fokusiranje.
So this idea of harnessing focused ultrasound to treat lesions in the brain is not new at all. When I was born, this idea was already conceived by pioneers such as the Fry brothers and Lars Leksell, who is know actually as the inventor of the gammaknife. But you may not know that he tried to perform lobotomies in the brain, noninvasively, with focused ultrasound in the '50s. He failed, so he then invented the gammaknife. And it makes you ponder why those pioneers failed. And there was something fundamental that they were missing. They were missing the vision. It wasn't until the invention of the MR and really the integration of MR with focused ultrasound that we could get the feedback -- both the anatomical and the physiological in order to have a completely noninvasive, closed-loop surgical procedure.
Ta koncept uporabe usmerjenega ultrazvoka za zdravljenje možganskih okvar pa sploh ni nov. Ko sem se rodil, so se s to idejo že ukvarjali pionirji, kot sta brata Fry in Lars Leksell, danes znan kot izumitelj gama noža. Morda pa niste vedeli, da je v petdesetih letih poskušal izvajati možgansko lobotomijo na neinvaziven način z usmerjenim ultrazvokom. Ni mu uspelo, je pa kasneje izumil gama nož. To da človeku misliti, zakaj tem pionirjem ni uspelo. Manjkalo jim je nekaj bistvenega. Manjkala jim je vizija. Šele z odkritjem slikanja z magnetno resonanco (MRI) in njeno združitvijo z usmerjenim ultrazvokom smo dobili odziv, tako anatomski kot fiziološki, in tako ustvarili popolnoma neinvaziven, zaprtozančni kirurški poseg.
So this is how it looks, you know, the operating room of the future today. This is an MR suite with a focused ultrasound system. And I will give you several examples. So the first one is in the brain. One of the neurological conditions that can be treated with focused ultrasound are movement disorders, like Parkinson's or essential tremor. What is typical to those conditions, to essential tremor for example, is inability to drink or eat cereal or soup without spilling everything all over you, or write legibly so people can understand it, and be really independent in your life without the help of others.
Tako je torej danes videti operacijska soba prihodnosti. To je prostor za MRI s sistemom usmerjenega ultrazvoka. Dal vam bom nekaj primerov. Začnimo z možgani. Ena od nevroloških okvar, ki jo lahko na tak način zdravimo, so motnje gibanja, kot sta Parkinsonova bolezen ali esencialni tremor (ET) Za take motnje, kot na primer pri esencialnem tremorju, je značilno, da bolnik ne zmore piti ali jesti juhe ali kosmičev, ne da bi se polil, ali pisati dovolj čitljivo, da bi lahko za njim brali, oz. biti v življenju neodvisen in živeti brez pomoči okolice.
So I'd like you to meet John. John is a retired professor of history from Virginia. So he suffered from essential tremor for many years. And medication didn't help him anymore. And many of those patients refused to undergo surgery to have people cut into their brain. And about four or five months ago, he underwent an experimental procedure. It is approved under an FDAIDE at the University of Virginia in Charlottesville using focused ultrasound to ablate a point in his thalamus. And this is his handwriting. "On June 20th," if you can read it, "2011." This is his handwriting on the morning of the treatment before going into the MR So now I'll take you through [what] a typical procedure like that looks like, [what] noninvasive surgery looks like.
Predstavljam vam Johna. John je upokojeni profesor zgodovine iz Virginie. Esencialni tremor ga je zaznamoval mnogo let, zdravila pa mu niso več pomagala. Veliko takšnih bolnikov je zavrnilo operacijo, saj niso želeli posegov na možganih. Pred štirimi ali petimi meseci pa je John sodeloval v poskusnem postopku. Uporabo postopka v raziskovalne namene je odobril odbor Ministrstva za zdravje na virginijski univerzi v Charlottesvillu, in tako smo z usmerjenim ultrazvokom uničili delček tkiva v njegovem talamusu. To je njegova pisava. "Dvajsetega junija," če lahko preberete, "leta 2011". To je njegova pisava na jutro posega, pred vstopom v prostor za MRI. Pokazal vam bom, kako deluje tak tipičen postopek oz. neinvazivni kirurški poseg.
So we put the patient on the MR table. We attach a transducer, in this case, to the brain, but if it will be a different organ, it will be a different transducer attached to the patient. And the physician will then take a regular MR scan. And the objective of that? I don't have a pointer here, but you see the green, sort of rectangle or trapezoid? This is the sort of general area of the treatment. It's a safety boundary around the target. It's a target in the thalamus. So once those pictures are acquired and the physician has drawn all the necessary safety limits and so on, he selects basically a point -- you see the round point in the middle where the cursor is -- and he presses this blue button called "sonicate." We call this instance of injecting the energy, we call it sonication. The only handwork the physician does here is moving a mouse. This is the only device he needs in this treatment.
Pacient leži na mizi za slikanje z magnetno resonanco. V tem primeru prevodnik usmerimo na možgane, če pa bi šlo za drug organ, bi uporabili tudi drugačen prevodnik. Zdravnik nato opravi običajno slikanje z magnetno resonanco. Kaj je cilj tega? Ne morem pokazati na sliko, a vseeno lahko vidite zelen trapezoidni okvir. To je nekakšno splošno območje posega. Predstavlja varnostno mejo okrog točke, ki jo ciljamo. Ta točka je v talamusu. Ko te slike pridobimo in ko zdravnik označi vse potrebne varnostne meje, izbere določeno točko -- okroglo točko v sredini, ki jo označuje puščica -- in pritisne na modro tipko "Soniciraj". Ta način injiciranja energije imenujemo ultrazvočna sonikacija. Edino delo zdravnikovih rok je pri tem premikanje miške. To je edina naprava, s katero upravlja.
So he presses "sonicate," and this is what happens. You see the transducer, the light blue. There's water in between the skull and the transducer. And it does this burst of energy. It elevates the temperature. We first need to verify that we are on target. So the first sonication is at lower energy. It doesn't do any damage, but it elevates the temperature by a few degrees. And one of the unique capabilities that we leverage with the MR is the ability to measure temperature noninvasively. This is really a unique capability of the MR. It is not being used in regular diagnostic imaging. But here we can get both the anatomical imaging and the temperature maps in real time. And you can see the points there on the graph. The temperature was raised to 43 degrees C temporarily. This doesn't cause any damage. But the point is we are right on target. So once the physician verifies that the focus spot is on the target he has chosen, then we move to perform a full-energy ablation like you see here. And you see the temperature rises to like 55 to 60 degrees C. If you do it for more than a second, it's enough to basically destroy the proteins of the cells.
Ko pritisne "Soniciraj", se zgodi sledeče. Prevodnik je svetlo modre barve. Med njim in lobanjo je voda. Ustvari se izbruh energije, s čimer temperatura naraste. Najprej se moramo prepričati, da imamo pravo točko. Prva sonikacija poteka z nižjo energijo. Ne povzroči nobene škode, pač pa dvigne temperaturo za nekaj stopinj. Ena od enkratnih sposobnosti, ki jih dosežemo z magnetno resonanco, je neinvazivno merjenje temperature. To je enkratna sposobnost magnetne resonance, ki pa se ne uporablja pri običajnem diagnostičnem slikanju. V našem primeru pa pridobimo anatomsko sliko in temperaturni profil v danem trenutku. Na grafu lahko vidite točke. Temperatura se je dvignila na začasnih 43°C. To ne povzroči nobene škode. Pomembno pa je, da ciljamo na pravo točko. Ko torej zdravnik potrdi, da je točka fokusiranja prava, se izvede uničenje delčka tkiva s polno močjo, kot vidite tu. Temperatura se povzpne med 55 in 60 stopinj Celzija. Če to traja več kot eno sekundo, je jakost dovolj močna, da uniči celične beljakovine.
This is the outcome from a patient perspective -- same day after the treatment. This is an immediate relief. (Applause) Thank you. John is one of [about] a dozen very heroic, courageous people who volunteered for the study. And you have to understand what is in people's mind when they are willing to take the risk. And this is a quote from John after he wrote it. He said, "Miraculous." And his wife said, "This is the happiest moment of my life." And you wonder why. I mean, one of the messages I like to carry over is, what about defending quality of life? I mean, those people lose their independence. They are dependent on others. And John today is fully independent. He returned to a normal life routine. And he also plays golf, like you do in Virginia when you are retired. Okay, so you can see here the spot. It's like three millimeters in the middle of the brain. There's no damage outside. He suffers from no neurodeficit. There's no recovery needed, no nothing. He's back to his normal life.
In to je rezultat s pacientovega stališča še isti dan po posegu. Gre za takojšnje izboljšanje. (Aplavz) Hvala. John je en od okrog ducata zelo pogumnih, herojskih ljudi, ki so se javili za sodelovanje v raziskavi. Treba je razumeti, o čem razmišljajo ljudje, ki se odločijo tvegati. John je, potem ko je znova napisal sporočilo, dejal, "Neverjetno." Njegova žena je rekla, "To je najsrečnejši trenutek mojega življenja." Vprašate se, zakaj. Eno od sporočil, ki ga želim posredovati, je pomen ohranjanja kakovosti življenja. Ti ljudje so namreč izgubili svojo samostojnost. Odvisni so od pomoči drugih. John pa je danes v celoti samostojen in nadaljuje z vsakodnevno rutino. Igra tudi golf, kot običajno počnejo upokojeni v Virginiji. Tu lahko vidite točko. Meri približno tri milimetre v središču možganov. Okrog nje ni poškodb. Ni več okvar živčevja. Po posegu ne potrebuje niti okrevanja, pač pa se vrne v običajno življenje.
Let's move now to a more painful subject. Pain is something that can make your life miserable. And people are suffering from all kinds of pain like neuropathic pain, lower-back pain and cancer pain from bone metastases, when the metastases get to your bones, sometimes they are very painful. All those I've indicated have already been shown to be successfully treated by focused ultrasound relieving the pain, again, very fast. And I would like to tell you about PJ. He's a 78 year-old farmer who suffered from -- how should I say it? -- it's called pain in the butt. He had metastases in his right buttock, and he couldn't sit even with medication. He had to forgo all the farm activities. He was treated with radiation therapy, state-of-the-art radiation therapy, but it didn't help. Many patients like that favor radiation therapy.
Poglejmo si sedaj bolj občutljivo področje. Bolečina je nekaj, kar vam lahko zagreni življenje. Ljudje trpijo zaradi vseh vrst bolečine, od nevropatske bolečine, bolečine v križu, do onkološke bolečine metastaz na kosteh, kjer lahko postanejo izjemno boleče. Vsi ti tipi bolečin so bili dokazano uspešno zdravljeni z usmerjenim ultrazvokom, ki je zelo hitro odpravil bolečino. Rad bi vam predstavil še PJ-jev primer. PJ je 78-letni kmet, ki je imel -- kako naj to povem? -- bolečino v zadnjici. Imel je metastaze na desni strani, zaradi česar ni mogel sedeti niti ob uporabi zdravil. Moral se je odpovedati vsem dejavnostim na kmetiji. Zdravili so ga z obsevanjem, najsodobnejšim obsevanjem, a mu ni pomagalo. Veliko takih pacientov se odloči za obsevanje.
And again, he volunteered to a pivotal study that we ran worldwide, also in the U.S. And his wife actually took him. They drove like three hours from their farm to the hospital. He had to sit on a cushion, stand still, not move, because it was very painful. He took the treatment, and on the way back, he drove the truck by himself. So again, this is an immediate relief. And you have to understand what those people feel and what their family experiences when it happens. He returned again to his daily routine on the farm. He rides his tractor. He rides his horse to their mountain cabin regularly. And he has been very happy.
Tudi on je prostovoljno sodeloval v osrednji raziskavi, ki je potekala po celem svetu, tudi v ZDA. Pripeljala ga je njegova žena. Od kmetije do bolnišnice sta se vozila tri ure. Moral je sedeti na blazini in se ne premikati, saj je bilo preveč boleče. Po posegu je na poti na kmetijo sam vozil tovornjak. Še enkrat gre torej za takojšnje izboljšanje. Treba je upoštevati, kako se ti ljudje počutijo in kaj občutijo njihove družine, ko poseg uspe. PJ se je vrnil k svoji dnevni rutini na kmetiji. Sam vozi traktor, pogosto celo jaha na konju do svoje koče v hribih. Res je srečen.
But now, you ask me, but what about war, the war on cancer? Show us some primary cancer. What can be done there? So I have good news and bad news. The good news: there's a lot that can be done. And it has been shown actually outside of the U.S. And doing that in the U.S. is very painful. I don't see, without this nation taking it as some collective will or something that is a national goal to make that happen, it will not happen. And it's not just because of regulation; it's because of the amount of money needed under the current evidence-based medicine and the size of trials and so on to make it happen.
Sedaj pa vas zanima, ali lahko s tem napovemo vojno raku? Kaj lahko storimo v začetnem stadiju rakavih obolenj? Imam dobro in slabo novico. Dobra je, da se lahko stori marsikaj. To smo dokazali izven ZDA. V ZDA je namreč take posege zelo težko opravljati. Bojim se, da če ne bo ta narod tega sprejel kot skupno željo ali kot cilj celega naroda, da bi to omogočil, bodo taki posegi nemogoči. Razlog niso samo predpisi, pač pa predvsem količina denarja, zahtevana v današnjem zdravstvu, ki temelji na dokazih, in za obsežne raziskave, ki to onemogoča.
So the first two applications are breast cancer and prostate cancer. They were the first to be treated by focused ultrasound. And we have better-than-surgery results in breasts. But I have a message for the men here. We heard here yesterday Quyen talking about the adverse event trait in prostate cancer. There is a unique opportunity now with focused ultrasound guided by MR, because we can actually think about prostate lumpectomy -- treating just the focal lesion and not removing the whole gland, and by that, avoiding all the issues with potency and incontinence. Well, there are other cancer tumors in the abdomen -- quite lethal, very lethal actually -- pancreas, liver, kidney. The challenge there with a breathing and awake patient -- and in all our treatments, the patient is awake and conscious and speaks with the physician -- is you have to teach the MR some tricks how to do it in real time. And this will take time. This will take two years.
Najprej smo ta način uporabili pri raku dojk in raku prostate. Na teh dveh vrstah raka smo najprej izvedli postopek. Pri raku dojk so rezultati boljši kot pri operaciji. Imam pa tudi sporočilo za moške. Včeraj je tu Quyen govorila o neželenih dogodkih pri raku prostate. Tu imamo izjemno priložnost uporabe usmerjenega ultrazvoka, ki ga vodi MR, saj si dejansko lahko zamislimo lumpektomijo prostate, s čimer bi zdravili le glavno poškodbo brez ostranitve celotne žleze in se tako izognili vsem težavam s potenco in inkontinenco. Tu imamo še druge rakave tumorje v trebuhu, ki jih je pravzaprav zelo malo -- rak na trebušni slinavki, jetrih in ledvicah. Izziv pri tem je -- ob pacientu, ki diha in je buden, in tako kot pri vseh naših posegih zavestno govori z zdravnikom -- da naučimo napravo za magnetno resonanco, kako naj poseg izvede ob pravem času. To pa bo terjalo čas. Trajalo bo približno dve leti.
But I have now a message to the ladies. And this is, in 2004, the FDA has approved MR-guided focused ultrasounds for the treatment of symptomatic uterine fibroids. Women suffer from that disease. All those tumors have heavy bleeding during periods, abdominal pressure, back pain, frequent urination. And sometimes, they cannot even conceive and become pregnant because of the fibroid. This is Frances. She was diagnosed with a grapefruit-sized fibroid. This is a big fibroid. She was offered a hysterectomy, but this is an inconceivable proposition for someone who wants to keep her pregnancy option. So she elected to undergo a focused ultrasound procedure in 2008. And in 2010, she became a first-time mother to a healthy baby. So new life was born.
Imam pa tudi sporočilo za dame. Leta 2004 je Ministrstvo za zdravje odobrilo uporabo usmerjenega ultrazvoka z magnetno resonanco za zdravljenje simptomatskih materničnih fibroidov. Ženske zbolijo za to boleznijo. Za te tumorje je značilno močno krvavenje v času perila, hude bolečine v trebuhu in hrbtu ter pogosto uriniranje. Včasih celo ne morejo spočeti otroka in zanositi zaradi fibroidov. To je Frances. Odkrili so ji fibroid v velikosti grenivke. Gre za velik fibroid. Ponudili so ji histerektomijo, kar pa je nesprejemljiv predlog za nekoga, ki želi nekoč zanositi. Zato se je leta 2008 odločila za poseg z usmerjenim ultrazvokom. Leta 2010 je postala mlada mamica zdravi dojenčici. Rodilo se je novo življenje.
(Applause)
(Aplavz)
So in conclusion, I'd like to leave you with actually four messages. One is, think about the amount of suffering that is saved from patients undergoing noninvasive surgery, and also the economical and emotional burden removed from their families and communities and the society at large -- and I think also from their physicians, by the way. And the other thing I would like you to think about is the new type of relationship between physician and patients when you have a patient on the table [who] is awake and can even monitor the treatment. In all our treatments, the patient holds a stop sonication button. He can stop the surgery at any moment.
Za konec imam za vas štiri sporočila. Prvič, pomislite, koliko trpljenja prihranimo pacientom v postopku neinvazivnega posega, in koliko finančnega in čustvenega bremena prihranimo njihovim družinam, skupnostim in družbi nasploh ter nenazadnje tudi njihovim zdravnikom. Drugič, rad bi, da razmislite o novi vrsti odnosa med zdravniki in pacienti, ko je pacient na mizi buden in preko zaslona spremlja poseg. Pri vseh naših posegih ima pacient dostop do gumba, ki ustavi sonikacijo. Poseg lahko prepreči, kadar želi.
And with that note, I would like to thank you for listening.
S to mislijo se vam zahvaljujem za pozornost.
(Applause)
(Aplavz)