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.
Tijekom posljednjih 13 godina -- jedne, tri, 13 godina -- bio sam dio jedinstvenog tima u InSightec-u u Izraelu i partneri iz cijelog svijeta zbog provođenja ove ideje, ovog koncepta, neinvazivne operacije, od istraživačkog laboratorija do rutinske kliničke upotrebe. I to je ono o čemu ću vam govoriti. 13 godina -- neki od vas mogu suosjećati s tom brojkom. Za mene , danas, ovaj dan, ovo je poput druge bar mitzve.
(Laughter)
(Smijeh)
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.
Dakle, ovaj san je zapravo omogućen konvergencijom dviju poznatih tehnologija. Jedna je fokusirani ultrazvuk, a druga je magnetna rezonanca koja omogućava slikoviti prikaz. Pa, hajdemo prvo razgovarati o fokusiranom ultrazvuku. Ja u ruci držim fantoma koji predstavlja tkivo. Napravljen je od silikona. Proziran je, napravljen samo za vas. Kao što vidite, sve je netaknuto, potpuno prozirno. Sada ću vas odvesti do zvučnog laboratorija. Vidite fantoma u akvariju. Ovo je instalacija koju sam sastavio u laboratoriju fizike. Na desnoj strani vidite ultrazvučni transduser. Dakle, ultrazvučni transduser emitira zapravo ultrazvučnu zraku koja se fokusira unutar fantoma. OK, kada čujete klik, tad će se energija početi emitirati i vidjet ćete malu leziju unutar fantoma. OK, dakle, sve okolo je čitavo i netaknuto. Imamo samo leziju formiranu unutra. Zamislite da je ovo u vašem mozgu. Mi trebamo dosegnuti metu unutar vašeg mozga. Mi to možemo učiniti bez ozljeđivanja bilo kojeg tkiva. Ovo je, po mom mišljenju, prvi kosher hipokratični operacijski sustav.
(Laughter)
(Smijeh)
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.
OK, hajdemo malo pričati o ultrazvuku, o snazi ultrazvuka. Vi znate sve o slikama, je li tako, o ultrazvučnim slikama. I također znate o litotripsiji -- razbijanju bubrežnih kamenaca. Međutim, ultrazvuk može biti oblikovan da bude bilo što između, jer je on mehanička sila. U osnovi, to je sila koja djeluje na tkivo koje mu se preprečava. Tako da možete mijenjati intenzitet, frekvenciju, trajanje, oblik pulsa ultrazvuka kako bi oblikovao bilo što od zračnog kista do čekića. A ja ću vam pokazati višestruke primjene u polju medicine koje mogu biti omogućene samim fokusiranjem, fizikalnim fokusiranjem.
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.
Stoga, ova ideja o korištenju fokusiranog ultrazvuka za liječenje lezija na mozgu, nije uopće nova. Kada sam rođen, ova ideja je već bila začeta od strane pionira poput braće Fry i Larsa Leksella, koji je također poznat kao izumitelj gamma noža. Ali ono što možda ne znate je da je on pokušao izvesti lobotomiju mozga, neinvazivno, s fokusiranim ultrazvukom u pedesetima. On nije uspio, pa je onda izumio gamma nož. Zanima vas zašto ti pioniri nisu uspjeli. Tu je postojalo nešto osnovno što im je nedostajalo. Nedostajala im je slika. Tek nakon izuma MR-a i istinske integracije MR-a s fokusiranim ultrazvukom mogli smo dobiti povratnu informaciju -- i anatomsku i fiziološku s ciljem postignuća potpuno neinvazivne, operacije zatvorene petlje.
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.
Dakle, ovako izgleda operacijska sala iz budućnosti danas. Ovo je MR odijelo s fokusiranim ultrazvučnim sustavom. A ja ću vam dati nekoliko primjera. Dakle, prvi je na mozgu. Jedan od neuroloških stanja koji je moguće liječiti fokusiranim ultrazvukom su poremećaji motorike, poput Parkinsonovog ili esencijalnog tremora. Ono što je tipično za ta stanja, primjerice za esencijalni tremor, je nemogućnost pacijenata da piju ili jedu žitarice ili juhu bez prosipanja svega po sebi, ili da čitljivo pišu kako bi ljudi mogli razumjeti, te da su uistinu neovisni u svom životu bez pomoći drugih ljudi.
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.
Volio bih da upoznate Johna. John je umirovljeni profesor povijesti iz Virginie. On je bolovao od esencijalnog tremora mnogo godina. I lijekovi mu više nisu pomagali. I mnogi od tih pacijenata odbijaju podvrći se operaciji, dopustiti ljudima da im režu mozak. Prije četiri ili pet mjeseci, on je podvrgnut eksperimentalnom postupku. On je odobren od strane FDAIDE na Sveučilištu Virginia u Charlottesvillu koristeći fokusirani ultrazvuk kao oštricu, ciljna točka bila je u njegovom talamusu. A ovo je on rukom napisao. “Lipanj 20.,” ako možete pročitati “2011”. Ovo je rukom napisao u jutro tretmana prije odlaska na MR. Sada ću vam pokazati kako tipični postupak izgleda, kako neinvazivna operacija izgleda.
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.
Stavimo pacijenta na MR stol. Pričvrstimo transduser, u ovom slučaju na mozak, ali ako bi u pitanju bio drugi organ, bio bi drugačiji transduser pričvršćen na pacijenta. Zatim liječnici naprave normalanu MR sliku. Koja je svrha toga? Nemam pokazivač ovdje, ali možete li vidjeti zeleni pravokutnik ili trapez? To je glavna regija za tretman. Postoji sigurna granica oko mete. Meta je talamus. U onom trenutku kad se slike dobiju i liječnk nacrta sve potrebne osiguravajuće granice i tako dalje, on zapravo odabire točku -- vidite okruglu točku u sredini gdje je pokazivač -- i pritisne plavi gumb nazvan “ozvuči”. Mi taj trenutak ubrizgavanja energije zovemo ozvučivanje. Jedini ručni rad koji liječnik ovdje radi je pomicanje miša. To je jedini uređaj koji mu je potreban za ovaj tretman.
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.
Kad on pritisne “ozvuči” ovo se dogodi. Vidite transduser, svijetlo plavi. Ovdje je voda između lubanje i transdusera. Ona radi ovu eksploziju energije. To podiže temperaturu. Prvo moramo potvrditi da smo na meti. Tako da je prvo ozvučivanje na nižoj energiji. Ono ne radi nikakvu štetu, nego podiže temperaturu za nekoliko stupnjeva. Jedna od jedinstvenih sposobnosti MR-a je neinvazivna sposobnost mjerenja temperature. To je uistinu jedinstvena sposobnost MR-a. To se inače ne koristi u normalnoj dijagnostici. Ali ovdje, mi možemo dobiti i anatomski prikaz i temperaturne mape u stvarnom vremenu. Možete vidjeti točke ovdje na grafu. Temperatura je privremeno podignuta na 43 stupnja C. To ne uzrokuje nikakvu štetu. Bit ovoga je da smo točno na meti. Jednom kad liječnik potvrdi da je točka fokusa na meti izabrana, onda učinimo punoenergetsko odsijecanje kao što ovdje možete vidjeti. Možete vidjeti da temperatura raste na otprilike 55 do 60 stupnjeva C. Ako to radite duže od sekunde, to je dovoljno da uništite sve proteine u stanici.
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.
Ovo je ishod iz pacijentove perspektive -- isti dan nakon operacije. Ovo je trenuračno poboljšanje. (Pljesak) Hvala. John je jedan od desetak vrlo hrabrih ljudi koji su volontirali u ovoj studiji. Morate razumjeti što je tim ljudima na pameti kada su odlučni prihvatiti taj rizik. Ovo je Johnov citat nakon što je to napisao. Rekao je: „Ovo je čudo.“ A njegova žena je rekla : „Ovo je najsretniji trenutak moga života.“ Pitate se zašto. Hoću reći, jedna od poruka koju želim poslati je kako zaštititi kvalitetu života? Ti ljudi izgube svoju neovisnost. Ovisni su o drugima. Danas je John potpuno neovisan. Vratio se normalnoj životnoj rutini. Također igra golf, kao što se to radi u Virginiji kad si umirovljen. Ok, možete ovdje vidjeti ovu maglu. Otprilike 3 mm u sredini mozga. Nema štete vani. On ne boluje od neurološkog deficita. Nije potreban oporavak, ništa. Može se vratiti svom normalnom životu.
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.
Prijeđimo sad na bolniju temu. Bol može učiniti vaš život lošim. A ljudi pate od različitih bolova poput neuropatskih bolova, bolova u križima te bol koju izazivaju koštane metastaze, kada metastaze dođu do vašeg mozga, ponekad je vrlo bolno. Sve ovo što sam nabrojao pokazalo se da može biti uspješno liječeno fokusiranim ultrazvukom, uklanjajući bol, opet, vrlo brzo. Htio bih vam pričati o PJ. On je 78- godišnji farmer koji je bolovao od -- kako da to kažem? -- zove se bolovi u guzi. Imao je metastaze u svom desnom dijelu stražnjice, sjediti nije mogao čak ni s lijekovima. Morao je zaboraviti sve aktivnosti na farmi. Liječen je radioterapijom, najsuvremenijom radioterapijom, ali nije pomoglo. Mnogim pacijentima poput njega pomaže radioterapija.
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.
Dakle, on se prijavio za središnju studiju koju smo proveli širom svijeta, također u SAD-u. Zapravo ga je dovela njegova žena. Vozili su se oko tri sata od njihove farme do bolnice. Morao je sjediti na jastučiću, mirno stajati, bez micanja, jer je bilo vrlo bolno. Primio je tretman i na povratku on sam je vozio kamionet. Ponavljam, ovo je trenutačno poboljšanje. Morate razumjeti kako se ti ljudi osjećaju i što njihove obitelji iskuse kad se to dogodi. On se vratio svojoj dnevnoj rutini na farmi. Vozi traktor. Redovito jaše konja kad ide u njihovu planinsku kolibu. Te je vrlo sretan.
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.
Sad me pitate, ali što s ratom protiv raka? Pokaži nam neki primarni karcinom. Što bi se tu moglo učiniti? Imam dobre i loše vijesti. Dobre vijesti: postoji puno toga što se može učiniti. I to je zapravo pokazano izvan SAD-a. U SAD-u je to vrlo bolno. Ne vidim kako bi se to ostvarilo bez da ova nacija na to gleda kao nekakvu kolektivnu volju ili tako nešto što je nacionalni cilj koji se treba ostvariti. Nije samo zbog odredbi, također i zbog svote novca koja je potrebna na trenutnoj medicini utemeljenoj na dokazima te veličini kliničkih pokusa itd.
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.
Prve dvije primjene su rak dojke i rak prostate. Oni su prvi liječeni fokusiranim ultrazvukom. U slučaju dojke imamo rezultate koji su bolji od rezultata dobivenih operacijom. Ali ovdje imam poruku za muškarce. Jučer smo ovdje čuli Guillena kako govori o negativnom učinku poteza kod raka prostate. Sada postoji jedinstvena mogućnost s fokusiranim ultrazvukom nadgledanim MR-om jer sad zapravo možemo razmišljati o uklanjanju kvržica na prostati -- tretirajući samo fokalnu leziju te ne odstranjivanju cijele žlijezde te time izbjegavajući sve probleme s potencijom i inkontinencijom. Postoje i drugi tumori u abdomenu -- prilično malo, zapravo jako malo -- gušterača, jetra, bubreg. Izazov ovdje s budnim pacijentom koji diše -- a u svim našim tretmanima pacijent je budan i svjestan i priča s liječnikom -- je da moramo naučiti MR neke trikove kako da to napravimo u stvarnom vremenu. A to zahtjeva vremena. To traje dvije godine.
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.
Sada imam poruku za dame. U 2004. FDA je odobrila upotrebu MR-om nadziranog fokusiranog ultrazvuka za liječenje simptomatičnih mioma maternice. Mnoge žene boluju od ove bolesti. Svi ti tumori uzrokuju teška krvarenja tijekom menstruacijskog ciklusa, pritisak u abdomenu, bol u leđima, učestalo mokrenje. A ponekad, one ne mogu začeti i zatrudnjeti zbog mioma. Ovo je Frances. Diagnosticiran joj je miom veličine grejpa. To je velik miom. Ponuđeno joj je uklanjanje maternice, ali to je neprihvatljiv prijedlog nekomu tko želi zadržati opciju trudnoće. Stoga je izabrala podvrći se fokusiranom ultrazvuku u 2008. 2010. prvi put je postala majka zdravom djetetu. Tako je rođen novi život.
(Applause)
(Pljesak)
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.
U zaključku htio bih vas ostaviti zapravo s četiri poruke. Jedna je da razmislite o količini patnje od koje su spašeni pacijenti koji se podvrgnu neinvazivnoj operaciji, također i ekonomski i emocijalni teret kojeg su oslobođene njihove obitelji i zajednica te društvo općenito -- usput, također i njihovi liječnici. Druga stvar o kojoj bih htio da razmislite je novi odnos između pacijenta i liječnika kada imate pacijenta na stolu koji je budan i može čak pratiti tretman. U svim našim tretmanima, pacijent drži gumb za zaustavljanje ozvučivanja. On može prekinuti operaciju u bilo kojem trenutku.
And with that note, I would like to thank you for listening.
I s tom porukom htio bih vam zahvaliti na slušanju.
(Applause)
(Pljesak)