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.
Poslednjih trinaest godina, jedna, tri, trinaest godina, sam deo vanrednog tima u "InSightec"-u u Izraelu i partnera širom sveta, koji su posvećeni tome da ideja, koncept neinvazivne hirurgije, pređe iz faze istraživanja u rutinsku, kliničku praksu. O tome ću vam pričati. Trinaest godina, neki od vas možda saosećaju sa tim brojem. Ja se danas osećam kao da sam na svojoj drugoj Bar Micvi.
(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.
Spajanje dve poznate tehnologije je dovelo do ostvarivanja ovog sna. Jedna je usmereni ultrazvuk, a druga je magnetna rezonanca sa vizuelnim predstavljanjem. Prvo ćemo pričati o fokusiranom ultrazvuku. Držim u svojoj ruci fantoma, nešto što imitira tkivo. Napravljen je od silicijuma. Providan je i napravljen samo za vas. Vidite, čitav je i potpuno providan. Sada idemo na turu kroz akustičnu laboratoriju. Uočićete fantoma u akvarijumu. Ovo je konstrukcija koju sam postavio u laboratoriji za fiziku. Sa desne strane je provodnik ultrazvuka. Provodnik ultrazvuka odašilje ultrazvučni snop koji se fokusira unutar fantoma. Okej, kada čujete klik, to je momenat kada počinje emitovanje energije i uočićete malu leziju koja se formira unutar fantoma. Okej, sve oko njega je čitavo i netaknuto. Samo je jedna lezija napravljena unutra. Zamislite sada da je to u vašem mozgu. Moramo dospeti do ciljne tačke u vašem mozgu. Možemo to uraditi bez povrede tkiva. Smatram da je ovo prvi Hipokratov operacioni sistem košer tipa.
(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.
Okej, sada ćemo pričati malo o ultrazvuku, o snazi ultrazvuka. Znate sve o uslikavanju, zar ne, ultrazvučnom slikanju. Čuli ste i za litotripsiju (med.) to je razbijanje kamenja u bubregu. Ultrazvuk se može podesiti da bude bilo šta na toj skali jer je to mehanička sila. U suštini, to je sila koja deluje na tkivo kroz koje prolazi. Možete menjati jačinu, učestalost, trajanje, pulsni oblik ultrazvuka kako biste napravili bilo šta od aerosolne četkice do čekića. Pokazaću vam višestruke primene toga u medicini koje su ostvarive uz pomoć usmerenosti, fizičke usmerenosti.
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.
Ova ideja o korišćenju usmerenog ultrazvuka pri lečenju lezija u mozgu uopšte nije nova. Kada sam ja rođen, ideja je već sazrela u glavama pionira, npr. Fraj braće ili Larsa Leksela, koji je poznat kao pronalazač gama-noža. Možda ne znate da je on pokušao da uradi neinvazivne lobotomije mozga, uz pomoć usmerenog ultrazvuka u 50-im. Nije uspeo, pa je potom izumeo gama-nož. To vas navodi da pažljivo razmislite zašto ti pioniri nisu uspeli. Postoji nešto osnovno što im je nedostajalo. Nedostajala im je vizija. Tek kada je otkrivena magnetna rezonanca (MR) i kada je došlo do integracije MR tehnologije i usmerenog ultrazvuka dobili smo povratnu informaciju-- i o anatomiji i o fiziologiji što je omogućilo da dođemo do potpuno neinvazivne hirurške metode po tipu zatvorenog kola.
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.
Znate, ovako izgleda operaciona sala budućnosti. Ovo je MR odeljenje sa sistemom fokusiranog ultrazvuka. Navešću vam nekoliko primera. Prvo ću pričati o mozgu. Jedni od neuroloških poremećaja koji mogu biti lečeni fokusiranim ultrazvukom su poremećaji pokreta, kao što je Parkinsonova bolest ili osnovni tremor. Ono što je karakteristično za ova stanja, na primer za osnovni tremor, jeste nesposobnost da pijete ili jedete pahuljice ili supu, a da ne prospete sve po sebi, ili da pišete čitko kako bi ljudi to mogli da pročitaju i da budete zaista nezavisni od pomoći drugih u svom životu.
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.
Hoću da vas upoznam sa Džonom. Džon je penzionisan profesor istorije iz Virdžinije. Patio je od osnovnog tremora godinama. Lekovi mu više nisu pomagali. Mnogi pacijenti odbijaju da se podvrgnu operaciji da ljudi ne bi seckali njihov mozak. Pre četiri ili pet meseci se podvrgao eksperimentalnom tretmanu. Odobren je od strane "FADAIDE" na Univerzitetu u Virdžiniji u Šarlotsvilu, a koristi se ultrazvukom kojim se uklanja deo u talamusu. Ovo je njegov rukopis. "20. juna," ukoliko možete da pročitate, "2011." Ovo je njegov rukopis jutra pre same operacije, pre odlaska na MR. Sada ću vam pokazati kako klasična procedura ovog tipa izgleda, kako neinvazivna hirurgija 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.
Postavili smo pacijenta na MR sto. Potom zakačimo provodnik, u ovom slučaju za mozak, ali ukoliko bi se radilo o drugom organu, drugi tip provodnika bismo zakačili za bolesnika. Potom će doktor uraditi prvi uobičajeni snimak MR-om. Cilj toga? Nemam pokazivač sa sobom, ali da li vidite zeleno, nešto kao kvadrat ili trapezoid? Ovo je opšte operativno polje. To je sigurnosna zona oko samog ciljnog mesta. Ovo je cilj u talamusu. U trenutku kada lekar dobije željenu sliku o svim neophodnim granicama bezbednosti i tako dalje, on odabira, u principu, tačku, vidite li ovu okruglu tačku u sredini gde se pokazivač nalazi, i potom pritisne plavo dugme koje se zove "sonikacija". Ovaj proces ubrizgavanja energije nazivamo sonikacijom. Sve što lekar uradi rukama ovde je pomeranje miša. To je jedini instrument koji mu je neophodan za 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.
Kada pritisne dugme za sonikaciju, desi se sledeće. Vidite provodnik, u svetlo plavoj boji. Između provodnika i lobanje se nalazi voda. Dolazi do ove eksplozije energije. To povišava temperaturu. Prvo moramo da proverimo da zaista gađamo ciljanu tačku. Prva sonikacija se izvodi uz manju količinu energije. Ne čini nikakvu štetu, ali povišava temperaturu za nekoliko stepeni. Jedna od osobenosti primene MR tehnologije jeste mogućnost neinvazivnog merenja temperature. Ovo je zaista jedinstvena sposobnost MR tehnike. Ne koristi se za uobičajeno dijagnostičko uslikavanje. Uz pomoć ovoga možemo doći do slika anatomije i mape temperatura u stvarnom vremenu. Možete uočiti te tačke na grafikonu. Temperatura je privremeno povišena na 43 stepena Celzijusa. Ovo ne dovodi ni do kakvih oštećenja. Poenta je u tome da gađamo ciljano mesto. U trenutku kada lekar potvrdi da je zadata tačka na cilju koji je izabrao, sledeći korak je amputacija punom energijom kao što ovde možete videti. Vidite porast temperature do od prilike 55 do 60 stepeni Celzijusa. Ukoliko to radite duže od sekunde, to je dovoljno da uništi sve proteine u ćelijama.
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.
Ovako rezultat izgleda iz persepktive pacijenta, istog dana nakon tretmana. Ovo je momentalno olakšanje. (aplauz) Hvala. Džon je jedan od desetak veoma hrabrih ljudi, heroja, koji su volontirali za ovu studiju. Morate razumeti šta je u glavi ovih ljudi kada požele da preuzmu takav rizik. Sada ću citirati Džona nakon što je ovo napisao. On je rekao: "Ovo je čudo." Njegova žena je rekla: "Ovo je najsrećniji trenutak u mom životu." Pitate se zašto. Znate, jedna od poruka koju želim da prenesem jeste, šta je sa zaštitom kvaliteta života? Znate, ovi ljudi izgube svoju nezavisnost. Oni zavise od drugih. Džon je danas potpuno nezavistan. Vratio se uobičajenom stilu života. On takođe igra golf, jer je to ono što radite u Virdžiniji kada se penzionišete. Okej, ovde možete uočiti naznačeni region. U sredini mozga, veličine oko tri mm. Spolja nema oštećenja. Ne pati od neurodeficita. Oporavak nije potreban, ništa se ne zahteva. Vratio se svom uobičajenom 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.
Sada ćemo pričati o bolnijem predmetu. Bol je nešto što može učiniti život nepodnošljivim. Ljudi pate od različith vrsta bola, kao što je neuropatski bol, bol u donjem delu kičme, bol nastao usled koštanih metastaza što se dešava kada rak metastazira u kostima, sve to je ponekad neopisivo bolno. Za sve ove vrste bola koje sam naveo je već pokazano da mogu biti uspešno lečene pomoću usmerenog ultrazvuka koji olakšava osećaj bola veoma brzo. Voleo bih da vam pričam o PiDžej. On je sedamdesetosmogodišnji poljoprivrednik koji je bolovao od - kako bih to nazvao? - naziva se bol u guzici. Rak je kod njega metastazirao na desnom guzu, i nije mogao da sedi čak ni uz pomoć lekova. Morao je da ostavi sve poslove na imanju. Lečen je radio-terapijom, najsavremenijom radio-terapijom, ali to nije pomoglo. Mnogi takvi bolesnici glasaju za radio-terapiju.
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.
Ponovo, on je volontirao za važnu studiju koju sprovodimo širom sveta, pa i u Sjedinjenim Državama. Ustvari, njegova žena ga je dovezla. Vozili su oko tri sata od njihovog imanja do bolnice. Morao je da sedi na jastuku, da mirno stoji, da se ne kreće, jer je bilo previše bolno. Podvrgao se operaciji, i pri povratku kući on je vozio kamion. Još jednom, ovo je momentalno olakšanje. Morate razumeti kako se ti ljudi osećaju i šta njihove porodice dožive kada se to dogodi. On se ponovo vratio svom svakodnevnom ritmu na imanju. Vozi svoj traktor. Redovno jaše konja do njihove brvnare na planini. Veoma je srećan.
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.
Sada ćete me pitati kakav to uticaj ima na borbu protiv raka? Pokaži nam rezultate na primarnom raku. Šta se tu može uraditi? Pa, imam dobre i loše vesti. Dobre vesti su da se svašta može učiniti. To je ustvari bilo pokazano van Sjedinjenih Država. Veoma je naporno to uraditi u Sjedinjenim Državama. Ne vidim da će se to desiti ovde, iako je ovo nacija kojoj je zajednički testament, ili gde je nacionalni cilj baš taj da se pobedi rak. To nije samo zbog regulacija. Ulogu u ostvarenju ovog cilja ima i količina novca koja je danas neophodna za medicinske dokaze, i velike studije.
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 dve primene su u lečenju raka dojke i raka prostate. To su prvi pokušaji lečenja usmerenim ultrazvukom. Imamo bolje rezultate nego klasična hirurgija u slučaju raka dojki. Takođe imam i poruku za mušarce. Juče je Kvijen govorila o nepoželjnim, sporednim efektima pri lečenju raka prostate. Sada imamo jedinstvenu priliku da uz pomoć usmerenog ultrazvuka i MR tehnologije razmišljamo o procesu lampektomije prostate (med.) o odstranjivanju samo određenog dela a ne cele žlezde, i na taj način možemo zaobići probleme potentnosti i inkontinencije (med.). Postoje i drugi tipovi raka u stomaku- koji su veoma mali, zaista veoma mali-- rak gušterače, jetre, bubrega. Izazov u ovoj proceduri je u tome što pacijent diše i budan je- u svim našim tretmanima su pacijenti budni i svesni i pričaju sa lekarom-- izazov je u tome da MR treba podučiti nekim trikovima kako sve to uraditi u stvarnom vremenu. Za ovo je neophodno vreme. Neophodne su dve 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. Ovo se dešava u 2004. kada je FDA odobrio usmereni ultravuk, navođen MR tehnikom za lečenje simptomatskih fibroida materice. Žene pate od te bolesti. Ove tumore karakterišu obilna krvarenja u toku ciklusa, pritisak u stomaku, bol u leđima, česti nagoni za mokrenjem. Ponekada ne može doći do začeća i trudnoće usled fibroida. Ovo je Frensis. Uspostavljeno je da ima fibroid veličine grejpfruta. To je veliki fibroid. Predložena joj je histerektomija, ali to je neprihvatljiv predlog za nekoga ko želi i dalje da rađa. Odlučila je da se podvrgne tretmanu usmerenim ultrazvukom u 2008. 2010. je postala prvorotka i ima zdravu bebu. Novi život je rođen.
(Applause)
(aplauz)
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.
Na kraju, voleo bih da zaključim sa četiri poruke. Prva, razmislite o pacijentima koji su pošteđeni patnje uz pomoć neinvazivne hirurgije, a i o značajnom ekonomskom i emocionalnom rasterećenju njihovih familija i zajednica kao i celog društva- a čini mi se i njihovih lekara, uzgred budi rečeno. Često razmišljam i o drugoj stvari koja se tiče novog tipa odnosa između lekara i pacijenata, kada je pacijent budan na operaciom stolu i može čak da prati tretman. U svim našim tretmanima, pacijent ima u rukama dugme za prekid sonikacije. Može da stopira operaciju u bilo kom trenutku.
And with that note, I would like to thank you for listening.
Sa tim bih završio. Hvala na pažnji.
(Applause)
(aplauz)