solution to accomplishment in the same way Thomas Edison discovered the solution to the electric light relentlessly indefatigably implacably until the truth which had been there all the time was revealed to him his second important ability was the knack or skill of writing about his findings in such a way that it was instantly understood intellectually but what is perhaps even


more important for this particular subject understood emotionally as well on the last page of Think and Grow Rich was read the hand which put the book down on the table was a different hand the man who then stood and walked out into the world was a different a changed man the suffocating entangling webs of self-imposed frustration and interaction had fallen away and now the way was clear the man

Napoleon Hill's Think & Grow Rich  Condensed and Narrated by Earl Nightingale


was now the possessor of the unique unseen talent for turning dreams into reality thoughts into things so called fate of the idle effects of exterior circumstances were no longer in command he who had been a passenger was now suddenly the captain to begin we have to understand the simple truth the principle or philosophy which lies is the supporting structure of this work


unless whatever it is you build is based on truth you will end with the entire structure fallen and scattered about you like the armor of Homer's ancient warriors it simply cannot stand it cannot withstand the test of time the reason thinking Grow Rich has withstood the test of time is because it rests on the broad clean foundation upon which may also be found every


accomplishment of man the clear unchallengeable fact that everything begins with an idea a philosophy based on the fact that riches of every kind begin with the State of Mind that one may start with nothing but thoughts ideas and organized plans thoughts are sings incredibly powerful things when mixed with definiteness of purpose persistence and the burning desire for


their translation into material objects or riches riches being whatever it is you happen to want wise men have been saying this for centuries and just recently Charles a sarami wrote the truth is that the human mind is as real and organism as any muscle in the body but far greater in potential power and like muscle fiber it can be strengthened to lead on to unimaginable is based if


you know what you want and if you want it strongly enough to muster the kind of persistence that simply cannot be stopped you most certainly achieve it by controlling your mind you can control your destiny here on earth with this as our foundation let's talk about napoleon hill's famous 13 proven steps to riches as found in his book Think and Grow Rich remembering of course that riches are


whatever it is you happen to want and right here let me make two important points the first is that whenever you listen to this record have a notebook handy and make notes as we go along the second is that this record was produced for your own personal use to go with you on your own exciting journey to play this record for a group will prove to be of only temporary help make sure you


have your own personal copy to play again and again particularly at those times when you may feel yourself getting off the track and now napoleon hill's famous 13 principles you will notice that we have separated each principles by bending them on the record in this way you're given quick access to any particular principle to which you may wish to return for reference the first


principle desire here is the starting point for all achievement that first step toward riches but it's right here that we so often run into a stumbling block a person will say I know what I desire but can I get it we'll get into this business of doubt later but once and for all let's clear up this point this point of whether or not you can accomplish that which you desire with


all your heart I think it was best expressed by Emerson who wrote there is nothing capricious in nature and the implanting of a desire indicates that its gratification is in the constitution of the creature that feels it in other words you would not have the desire unless you were capable of its achievement each of us has a built-in governor and our desires are modified by


our abilities and leanings whatever it is that you desire with all your heart understand once and for all that it can and should be yours in Think and Grow Rich Napoleon Hill cites example after example of why you're burning desire is nothing more than an accurate picture of what you will one day become so right here firmly establish in your mind that which you desire more than


anything else for as hell vicious put it by annihilating the desires you annihilate the mind every man without passions has within him no principle of action nor motive to act a good way to determine whether or not you really have a burning desire is to examine the way you go after it if you go after that which you think you desire tentatively timidly in an attempt to play it safe


you don't have a burning desire at all you can't get the second base if you keep one foot on first but if you're willing to burn your bridges behind you and say once and for all this is it this is what I will do and I will never retreat I'll never go back then you have the sort of desire that can only end in success it takes that kind of resolve to be able to keep


picking yourself up after there falls you're bound to take the only people who don't make mistakes are those who never try anything the timid feeders in the lagoon who never venture into the broad deep sea beyond well these principles will work for anything you may want a more harmonious home life a more successful career for our example let's say your desire happens to be more money


to better care for your family and provide for your future years to get your share of the prosperity that lies ahead Napoleon Hill gives us six definite practical steps to follow 1 fix in your mind the exact amount of money you desire it is not sufficient merely to say I want plenty of money be definite as to the amount there's a psychological reason for definiteness


which will be described in a subsequent principle number 2 determine exactly what you intend to give in return for the money you desire there's no such reality as something for nothing 3 establish a definite date when you intend to possess the money you desire and 4 create a definite plan for carrying out your desire and begin at once whether you're ready or not


to put this plan into action 5 write out a clear concise statement of the amount of money you intend to acquire name the time limit for its acquisition state what you intend to give and return for the money and describe clearly the plan through which you intend to accumulate it 6 read your written statement aloud twice daily once just before retiring at night and


once after a rising in the morning as you read see and feel and believe yourself already in possession of the money or whatever your goal happens to be it's important that you follow these instructions to the letter play this part of the record over until you have it down to your satisfaction for this is by far the most important of the 13 principles and this chapter of


the book ends with these words through some strange and powerful principle of mental chemistry which she has never divulged nature wraps up in the impulse of strong desire that's something which recognizes no such word is impossible and accepts no such reality as failure the second principle is faith you never would have even thought of your main desire unless faith were tugging at your


mind and if you find it difficult at times to have faith in yourself you can be certain that you can have faith in these principles Napoleon Hill writes faith is a state of mind which may be induced or created by affirmation or repeated instructions to the subconscious mind through the principle of conscious Auto suggestion conscious auto suggestion simply means a


suggestion by yourself to yourself just as an autobiography is a biography written by the person it's about by getting a mental image of yourself already having accomplished your main desire over and over again you will muster the faith you need faith is vital to accomplishment the emperor napoleon once said all the scholastic scaffolding falls as a ruined edifice before one


single word faith Pascal said faith affirms many things respecting which the senses are silent but nothing which they deny it is superior to their testimony but never opposed to it Goethe said epochs of faith are epics of fruitfulness but epochs of unbelief however glittering a barren of all permanent good and a Schlegel put it in actual life every great Enterprise begins with and takes


its first forward step in faith have faith that you can accomplish that which you seek for you would never have decided upon it unless it was meant for you to accomplish in his chapter on faith Napoleon Hill gives us a self-confidence formula first I know that I have the ability to achieve the object of my definite purpose in life therefore I demand of myself persistent


continuous action toward its attainment and I hear and now promise to render such action second I realize that dominant thoughts of my mind will eventually reproduce themselves in outward physical action and gradually transform themselves into physical reality therefore I will concentrate my thoughts for 30 minutes daily upon the task of thinking of the person I intend


to become thereby creating in my mind a clear mental picture of that person third I know through the principle of Auto suggestion any desire that I persistently hold in my mind will eventually seek expression through some practical means of attaining the object back of it therefore I will devote ten minutes daily to demanding of myself the development of self-confidence fourth I


have clearly written down a description of my definite chief aim in life and I will never stop trying until I have developed sufficient self-confidence for its attainment fifth I fully realize that no wealth or position can long endure unless built upon truth and justice therefore I will engage in no transaction which does not benefit all human effects I will succeed by


attracting to myself the forces I wish to use and the cooperation of other people I will induce others to serve me because of my willingness to serve others I will eliminate hatred envy jealousy selfishness and cynicism by developing love for all humanity because I know that a negative attitude toward others can never bring me success I will cause others to believe in me


because I will believe in them and in myself in rereading thinking Grow Rich so that I could write this condensation for recording I was forcibly struck all again by this great chapter on faith particularly the examples of how some of the world's greatest men have accomplished what appeared to be impossible through faith the third principle is Auto suggestion


now we've already touched on this this chapter the book tells us how through repeated suggestion the subconscious mind can be put to work for us it is the Faculty of being able to concentrate your mind on your burning desire until your subconscious mind accepts it as fact and begins to devise ways of bringing it about here is where hunches come from sudden flashes of thought or


inspiration guidance the instructions given in connection with the six steps in the second chapter will now be summarized and blended with the principles covered by napoleon hill's chapter on Auto suggestion first go into some quiet spot perhaps in bed at night close your eyes and repeat aloud so you may hear your own words the written statement of the amount of money you


intend to accumulate or a careful reaffirmation of whatever your goal happens to be the time limit for its accumulation and a description of the service or merchandise you intend to give in return for the money as you carry out these instructions see yourself already in possession of your goal for example suppose that you intend to accumulate fifty thousand dollars by


the 1st of January five years from now that you intend to give personal services in return for the money in the capacity of a Salesman your written statement of your purpose should be similar to the following by the first day of January 19 whatever it happens to be I will have in my possession fifty thousand dollars which will come to me in various amounts from time to time


during the interim in return for this money I will give the most efficient service of which I'm capable rendering the fullest possible quantity and the best possible quality of service in the capacity of salesmen of and here describe the product or service you intend to sell or whatever it is you do for a living it goes on I believe that I will have this money in my possession my


faith is so strong that I can now see this money before my eyes I can touch it with my hands it is now awaiting transfer to me at the time and in the proportion that I deliver the service I intend to Ren in return for it I am awaiting a plan by which to accumulate this money and I will follow that plan when it is received second repeat this program night and morning until you can see in


your imagination the money you intend to accumulate third place a written copy of your statement where you can see at night morning and read it just before retiring and upon arising until it's been memorized as you carry out these instructions you are applying the principle of auto suggestion the fourth principle is specialized knowledge it is here that I think Napoleon Hill makes a


very important point knowledge is power only to the extent that it is organized into a definite plan of action and directed to a definite end to quote from the book before you can be sure of your ability to transmute desire into its monetary equivalent you will require specialized knowledge of the service merchandise or profession which you intend to offer in


return for fortune perhaps you may need much more specialized knowledge than you have the ability or the information require and if this should be true you may bridge your weakness through the aid of your mastermind group more on this later but for now realize that you must learn all you can about your specialty set aside a definite time every day for learning more about what it is you do


for a living take the courses that are offered on your subject and associate with men who know your business well the fifth principle is imagination the imagination is literally the workshop where in our fashion all plans created by man the impulse the desire is given shape form and action through the aid of the imaginative Faculty of the mind it has been said that man can create


anything he can imagine as Napoleon Hill says and teaches whatever the mind of man can conceive and believe it can achieve man's only limitation within reason lies in his development and use of his imagination and subsequent motivation to action the great leaders of business industry finance and the great artists musicians poets and writers became great because they


developed the power of self motivation incidentally one of best books ever put together on this subject if not the greatest is success through positive mental attitude by Napoleon Hill and W Clement stone I suggest you get a copy from your bookstore at your earliest convenience if your bookstore happens to be out of the book you may obtain a copy by writing to the address on the label of


this record as you go about your daily work think constantly of ways in which it could be done better more efficiently think of the changes that are inevitable can they be made now and if you feel limited remember the words of the late Frank Lloyd Wright he said the human race built most nobly when limitations were greatest and therefore when most was required of imagination in order to


build it all limitations seemed to have always been the best friends of architecture as you build your future from this point onward don't concern yourself with limitations but remember that they may be your best friends since they require imagination if were to rise above them and this Beecher said the soul without imagination is what an observatory would be without a telescope


now if you turn this record over we'll get to the sixth principle the sixth principle is organized planning you have decided on your desire your goal now let's organize the plan for its accomplishment right on schedule let me quote again from Think and Grow Rich you have learned that everything man creates or acquires begins in the form of desire the desire is taken on


the first lap of its journey from the abstract to the concrete in the workshop of the imagination for plans for its transition are created and organized earlier you were instructed to take six definite practical steps as your first move in translating the desire for whatever you want into its physical equivalent one of these steps is the formation of a definite practical plan


or plans through which this transformation may be made one ally yourself with one or more persons a group of as many people as you may need for the creation and carrying out of your plan or plans for the accumulation of the money you've established as your goal making use of the mastermind principle this is important too before forming your mastermind Alliance


decide what advantages and benefits you may offer the individual members of your group in return for their cooperation no one will work indefinitely without some form of compensation although this may not always be in the form of money 3 arrange to meet with the members of your mastermind group at least twice a week and more often if possible until you have jointly perfected the necessary


plan or plans for the accomplishment of your goal 4 maintain perfect harmony between yourself and every member of your mastermind group keep in mind these facts first you're engaged in an undertaking of major importance to you to be sure of success you must have plans which are faultless second you must have the advantage of the experience education native ability and


imagination of other minds this is in harmony with the methods followed by every person who has risen above the average work at this until you have a well-executed formal plan for reaching your objective in this way you're never confused or wondering what you should do next every morning you know exactly what you're going to do and why it is in this chapter of thinking Grow Rich that


Napoleon Hill gives us his eleven qualities of leadership one unwavering courage two self-control 3 a keen sense of justice four definiteness of decision 5 definiteness of plans 6 the habit of doing more than paid for 7 a pleasing personality 8 sympathy and understanding 9 mastery of detail 10 willingness to assume full responsibility and 11 cooperation the chapter on organized planning is one of


the largest and most important in the book it goes without saying that a man without a plan to follow is like a ship without a course no place to go with disaster a probability the seventh principle decision the mastery of procrastination to quote accurate analysis of over twenty five thousand men and women who had experienced failure disclosed the fact that lack of decision was near the head


of the last of the thirty major causes of failure this is no mayor's statement of a theory in his effect procrastination the opposite of decision is a common enemy which every man must conquer analysis of several hundred people who had accumulated fortunes well beyond the million dollar mark disclosed the fact that every one of them had the habit of reaching decisions promptly and


of changing these decisions slowly if and when they were changed people who fail to accumulate money without exception have the habit of reaching decisions if at all very slowly and of changing these decisions quickly and often a definite objective makes reaching prompt decisions that much easier Napoleon Hill gives many examples one of which is the case of Henry Ford


one of Henry Ford's most outstanding qualities was his habit of reaching decisions quickly and definitely and changing them slowly this quality was so pronounced in the late mr. Ford that it earned form the reputation of being obstinate it was this quality which prompted mr. Ford to continue to manufacture his famous Model T the world's ugliest but for the time most


practical car when all of his advisors and many of the purchases of the car were urging him to change it perhaps he delayed too long in making the change but the other side of the story is that his firmness of decision yielded a huge fortune before the change in model became necessary and the company's certainly none the worse for today when you make up your mind stay with it the


majority of people who fail to make the grade are generally easily influenced by the opinions of others easily swayed they permit the newspapers and the gossiping neighbors to do their thinking for them opinions are the cheapest commodities on earth keep your own counsel when you begin to put into practice the principles we're describing here by reaching your own decisions and


following them take no one into your confidence except the members of your mastermind group and be very careful in your selection of this group that you choose only those who will be in complete sympathy and harmony with your purpose close friends and relatives while not meaning to do so often handicapped one through a opinions and sometimes through ridicule


thousands of men and women carry inferiority complexes with them all through life because some well-meaning but ignorant person destroyed their confidence through opinions or ridicule if a decision is worth anything at all it's worth sticking to until it's been completely worked the eighth principle persistence Napoleon Hill defines persistence as the power of will


willpower and desire when properly combined make an irresistible pair persistence to an individual is what carbon is to steel in uncounted thousands of cases persistence has stood as the difference between success and failure it is this quality more than any other that keeps the majority from great accomplishment they will try a thing but as soon as the going gets tough they


fold experience with thousands of people has proved that lack of persistence is a weakness common to the majority of men it is a weakness which may be overcome by effort if you are to accomplish the desire you've set for yourself you must form the habit of persistence things will get dark it will seem as though there's no longer any reason to continue everything in you will tell you to give


up to quit trying and it's right here that the men are separated from the boys it's right here that if you'll go that extra mile and keep going that the skies will clear and you'll begin to see the first signs of the abundance that is to be yours because you had the courage to persist with persistence will come success persistence is a state of mind therefore it can be cultivated like all


states of mind persistence is based upon definite causes among them these 1 definiteness of purpose knowing what you want to desire 3 self-reliance 4 definiteness of plans 5 accurate knowledge knowing that your plan is sound 6 cooperation sympathy understanding and harmonious cooperation with others tend to develop persistence 7 willpower 8 Hemet persistence is the


direct result of habit the ninth principle power of the mastermind it is in this section that Napoleon Hill describes the importance of forming a group of individuals sympathetic to your desire they may be individuals with similar plans a mastermind group can be made up of two or more individuals no two Minds ever come together without thereby creating a third a third invisible intangible force


which may be likened to a third mind you may have noticed many times that by discussing something with another individual you suddenly get good ideas as a result of this Association ideas you would not have gotten without this Association the same thing happens to the other person a lot of good ideas have been born in individual minds as a result of having met in committee associating with your


mastermind group is not meant as a means of letting others do your thinking for you far from it it is to stimulate your own thinking through the association with other minds no one knows everything the more sympathetic Minds you get together and by sympathetic I mean working for a common purpose the more related information is going to be available and great ideas are a


combination of related information so pick the member or members of your mastermind group with care make sure there are people you respect and who are hardworking and conscientious you have a lot of fun and you'll all reach your goals just that much sooner the tenth principle could be called enthusiasm that is the enthusiasm that comes from the channeling of all bodily drives into


positive worthwhile outlets it is in this chapter that Napoleon a describes the importance of the woman the one and only woman in the achievement of a worthwhile goal it seemed quite significant to mr. Hill that practically every great leader was a man whose achievements were largely inspired by a woman when things get tough and you can count on if they will you may be


deserted by what you thought were friends but if you've got a good woman you'll never be alone she'll be willing to start over again if necessary and she'll give you the new enthusiasm that comes through her faith in you having someone to love is having someone to share your success and accomplishment to give you the praise that all of us need from time to time a man can become


successful without a wife and family but all the real joy is taken out of it take care of your wife and children as your greatest possessions the 11th principle has to do with the subconscious mind the subconscious mind consists of a field of consciousness in which every impulse of thought that reaches the objective mind through any of the five senses is classified and recorded and from which


thoughts may be recalled or withdrawn as letters may be taken from a filing cabinet it receives and files sense impressions or thoughts regardless of their nature you may voluntarily plant in your subconscious mind any plan thought or purpose which you desire to translate into its physical or monetary equivalent the subconscious acts first on the dominating desires which have


been mixed with emotional feeling such as faith your subconscious mind works night and day through a method of procedure unknown to man the subconscious mind draws upon the forces of infinite intelligence for the power with which it voluntarily transmutes one's desires into their physical equivalent making use always of the most practical media by which this end may be


accomplished you cannot entirely control your subconscious mind but you can voluntarily hand over to it any plan desire or purpose which you wish transformed in a concrete form no one knows very much about what we call the subconscious or unconscious mind we do know that it is incalculably powerful and can solve our problems if we go about using it the right way and


the best way is to hold in your conscious mind as often as possible a clearer picture of yourself already having accomplished your goal you know what you want define it clearly and then project it on the motion picture screen of your mind hold it see yourself doing the things and having the things you'll have when your objective will have been reached do this as often as possible as you go


about your daily work and particularly at night just before you go to sleep and the first thing upon arising as you do this your subconscious will begin to lead you in the most logical ways toward your objective don't fight it follow your sudden hunches the ideas that come into your mind knowing that it's your subconscious trying to get through to your conscious mind if you keep at this


you'll be amazed and delighted by the wonderful ideas that just seem to come from nowhere in the next principle we'll talk some more about this sixth sense that seems to control the lives of the great men and women but it comes from a systemic triggering of the subconscious mind the lives of the great men and women which seem miraculous to the average person are nothing more than the


fulfillment of their burning desires through the power of their subconscious minds time means nothing to your subconscious a man could work steadily at his job for forty years and not accomplish as much as is possible in three or four years through the proper working of this principle your subconscious mind cannot remain idle if you fail to plant desires in your


subconscious mind it will feed upon the thoughts which reach it as a result of your neglect remember that you're living daily in the midst of all manner of thought impulses which are reaching your subconscious mind without your knowledge some of these impulses are negative some are positive you are now engaged in trying to help shut off the flow of negative impulses and to aid in


voluntarily influencing your subconscious mind through positive impulses of desire when you achieve this you will possess the key which unlocks the door to your subconscious mind bulwa wrote the man who succeeds above his fellows is the one who early in life clearly discerned his object and toward that object habitually directs his powers even genius itself is but fine


observation strengthened by fixity of purpose every man who observes vigilantly and resolves steadfastly grows unconsciously into genius the key word there is unconsciously know what you want decide once and for all that it will be yours remain steadfast on course propelled by faith and your subconscious or unconscious mind will do the rest the twelfth principle as outlined in


thinking Grow Rich by Napoleon Hill has to do with the brain if you had access to all the wealth in the world and took a penny you would be doing exactly what you very probably have been doing in the use of your brain nothing in the world is more pitiful than the misunderstanding by the average person of the power of his brain and the minds to which it is connected the conscious


and the subconscious you own in your brain the most marvelous miraculous inconceivably powerful force the world has ever known take for example the fact that the number of lines which connect the brain cells with one another equal a figure one followed by 15 million ciphers it has been determined that there are from ten to fourteen billion cells and the average human cerebral cortex it is


inconceivable that such a network of intricate machinery should be in existence for the sole purpose of carrying on the physical functions incidental to growth and maintenance of the physical body this is the mechanism that has given us the supersonic airplane our deep rocket probes into outer space the sciences the arts all that we know and use today and will use


tomorrow have hatched from this small grey mass each of us carries around do you can you doubt even for a moment that it can bring you and yours everything you want here on earth of course it can if you will recognize your power as an individual and stop acting like those who have never even thought about it give it the job you've decided to accomplish and watch it handle it the


thirteenth and final principle is called the sixth sense the sixth sense can be described as the sense through which infinite intelligence may and will communicate voluntarily without any effort from or demands by the individual this principle is the apex of the philosophy it can be assimilated understood and applied only by first mastering the other twelve principles


the sixth sense is that portion of the subconscious mind which has been referred to as the creative imagination it has also been referred to as the receiving through which ideas plans and thoughts flash into the mind the flashes are sometimes called punches or inspirations the sixth sense defies description it cannot be described to a person who has not mastered the other principles of


this philosophy because such a person has no knowledge and no experience with which the sixth sense may be compared the sixth sense is not something that one can take off and put on a twill ability to use this great power comes slowly through application of the other principles we've outlined many individuals come into a workable knowledge of the sixth sense even before


the age of 40 but more often the knowledge is not available until one is well past 50 and this for the reason that the spiritual forces with which the sixth sense is so closely related do not mature and become usable generally except through years of meditation self-examination and serious thought but begin to develop it now by applying the principles we've talked about here


remember this man can create nothing which he does not first conceived in the form of an impulse of thought mens thought impulses begin immediately to translate themselves into their physical equivalent whether those thoughts are voluntary or involuntary keep fear out of your mind by concentrating on the mental picture of your goal your greatest desire now I want to mention


that Think and Grow Rich as a book carries more endorsements by great men who knew of its truth than any other book of its kind ever written I'll touch on only a few all of these great men actually endorsed Napoleon Hills principles former President of the United States William Howard Taft FW Woolworth wrote that he had built his great chain of stores by applying many


of these principles Robert dollar who built the great dollar steamship line wrote if I had had this philosophy 50 years ago I suppose I could have accomplished all that I've done in less than half the time I sincerely hope the world will discover and reward you Samuel Gompers wrote that the mastery of these principles is the equivalent of an insurance policy


against failure President Woodrow Wilson John Wanamaker the merchant Prince wrote I know that your fundamentals are sound because I've been applying them in my business for more than 30 years George Eastman the world's largest maker of cash Thomas Edison Luther Burbank Theodore Roosevelt iam Statler john d rockefeller i think you know that the endorsements of these great men could not have been


bought with all the money in the world what we have been talking about here can change your life can bring you anything and everything worthwhile you want in life for yourself and your family cut yourself away from the average from the mediocre and chart your course on the dream in your heart these thirteen principles will never let you down as long as you use them and now it is with


great pleasure that i give you the author himself napoleon hill thank you era nightingale the message which you who are listening have just heard has brought you within three short steps of the supreme secret of success the same secret which has brought happiness peace of mind and financial success to countless thousands of people who have read Think and Grow Rich the same


secrets which has made master salesmen out of ordinary order takers and the same secret which has brought friendship love and marriage to men and women who have come under the spell of the thirteen principles which Earl Nightingale has just described you desire the better things of life or you wouldn't be listening to this record come with me then and I will help you


chart your course so you may acquire whatever it is that you desire most in life by following these instructions one condition your own subconscious mind to work for you while you sleep as well as when you are awake you can do this by playing this record to yourself every night just before you retire then before you go to sleep after hearing the record write out a clear statement of what you


wish to accomplish the following day and request your subconscious mind to work during the night and provide you with the plan you will need to achieve your purpose to form a personal mastermind group of two or more people who are closely associated with you they can be members of your family your business or your professional associates or people who work where you are employed and play


this record in their presence at least once a week after you have done this engaging friendly roundtable discussion of the thirteen success principles and requests each person in the group to participate and to look for inspirational ideas which may help him or her to become more successful three beginning now follow the habit of rendering more service and better service than that which is


expected of you and do it in a pleasing positive mental attitude this will make friends for you it will increase the value of your services and it will attract opportunities by which you may get from life whatever it is that you most desire follow these instructions to the letter and you ensure to see the day when you can express a prayer of gratitude for having


had the privilege of hearing and acting on the message which Earl Nightingale has given you through this record and now may I reach out across the space and the time which separate us and offer you a hand of friendship and a sincere prayer that you will be blessed with a richer and fuller life because of this message your big opportunity may be right where you are now follow these


good evening everybody my name is rose I'm with the Academy of Science st. Louis and we are one of the sponsors of tonight's talk along with the st. Louis Zoo and we're very pleased to be partnering with the zoo to bring you tonight science seminar before we get started this evening I'd like to tell you a little bit about the Academy of Science and who we are we're an

Reversing Time, Photoacoustics and Other Optical Breakthroughs in Biomedical Imaging


independent science organization we're supported entirely through community contributions and we've been around for a very long time since 1856 it's our mission to promote the public understanding of science and inspire the next generation and at venues throughout the region we do that by connecting science in the community through free and our very low-cost public talks so in


seminars and workshops and trips and tours that celebrate science at venues throughout the metropolitan st. Louis region and surrounding counties these trips tours and talks feature scientists and engineering professionals of both national and international renown in addition to advancing the public understanding of science excuse me as I had said it's our mission as well to


inspire the next generation we do that through a number of free and low-cost opportunities that are expressly for teams such as their teen science cafes teen cafes Youth Leadership Council and Junior Academy of Science the Junior Academy is a pre-professional stem membership organization for students in grades 6 through 12 that offers hands-on opportunities in science engineering and


medicine teens can attend unique behind-the-scenes explorations of leading engineering technology and science labs of our region you can access University Libraries participate in field opportunities in challenging and engaging science competitions for a full range of academic levels and Junior Academy members make real-world connections meeting top stem professionals so if you know a student


or students or you are a student in grades 6 through 12 with a love for science memberships in the Junior Academy make great holiday gifts you can find more information on the Academy and all of our community wide events by visiting our website at academy of science stl dot org you may also visit us on Facebook or Twitter or before you leave tonight pick up some of the literature that is


on the table just outside the auditorium I do want to mention a couple upcoming academy events you might have an interest in attending on Tuesday evening December 9 at the Missouri History Museum retired University of missouri-columbia associate professor of fisheries and wildlife sciences and the Nature Conservancy's Great Rivers partnership science advisor dr. David


gala talks about an ecological history of the Missouri River and 21st century challenges in the Big Muddy this event is free and open to the public you do not need to register to attend and then on January 28th on the Washington University Medical School campus and as part of our teen science cafe series radiology and biomedical engineering professor dr. Susan Lackey talks about


nanotechnology in the science of the small teen science cafes are open to all students in grades 6 through 12 they are interactive they are free and there is food but you do need to register to attend and you can do so by logging onto our website again at academy of science stl org you can find even more science opportunities talk some tours on our web site or listed on the event fliers and


Academy literature that is available for you to take with you before you leave this evening if you'd like to receive a notification of upcoming academy public lectures and events there are some enews sign-up sheets that will make their way around the audience if you are a student and you need to verify your attendance at tonight's talk there will be some verification cards that are available


following tonight's QA also out at the table outside the auditorium please turn off cell phone rings or any other electronic devices that might make noise during the program with all that said I'd like to introduce this evening speaker dr. Lee Hong Wong dr. Wong earned his BS and MS and optics from Zhang universities of Science and Technology in Wuhan China and his PhD in


electrical engineering from Rice University he is a fellow of the Academy of Science State Lewis and a recipient of the Academy's 2014 James bees outstanding st. Louis scientist award recognized for his seminal work in photoacoustic tomography and bio photonics he is currently the gene K berry distinct professor of biomedical engineering at Washington University in st. Louis and


his book biomechanical optics principles and imaging was one of the first text books in the field garnering the 2010 Joseph W Goodman book writing award dr. Wagner is also the co-author of a book on polarization and editor of the first book on photoacoustic tomography his laboratory invented or discovered get ready functional photoacoustic tomography 3d photo acoustic microscopy


the photo acoustic Doppler effect photoacoustic reporter gene imaging focused scanning microwave induced thermoacoustic tomography universal photoacoustic reconstruction algorithm frequency swept ultrasound modulated optical tomography time reversed ultrasonic Lian decoded optical focusing sonoluminescence tomography Miller matrix Oct article coherence computed


tomography and oblique incidence reflectometry his magic Harlow model of photon transport and scattering media is used worldwide he has published over 380 peer-reviewed articles and delivered 382 keynote plenary are invited talks he is prolific and well-known across the globe and we are very pleased to have him here with us tonight he's here with us to talk about photo acoustics and other


optical engineering breakthroughs in biomedical engineering on behalf of the academy of science news in the st. Louis Zoo won't you please join me in welcoming dr. Lee hongwol well thank you rose for the very kind introduction thank you all for coming here tonight I'll be talking about several technologies we've been working on in our lab our goal is to image biological


tissue using optical contrast starting from the motivations and challenges in our field in general I'll be talking about two major incarnations of photoacoustic tomography namely photoacoustic computed tomography and photo acoustic microscopy then I'll talk about some some of the newer technologies we've been working on time reversal and compressed ultra-fast


photography the very first question is why do we bother with light for imaging purposes you know when you walk to a hospital you go to your video department you'll see a lot of imaging modalities already MRI ultrasound and x-ray what not now first of all it's very safe to use light because we're receiving light or optical photons all the time every day so we're dealing with what's called


now ionizing radiation the radiation involves photons of very tiny energy you're talking about electron volts as a unit for photon energy so when you're talking about a cup of v's then the photons are not energetic enough to ionize molecules very safe but we use x-ray photons that are so energetic thousands of v's they'll knock off electrons out of molecules do


eyeliners tissue and cause problems such as DNA DNA damage and so the ionizing radiation parted of the EMR electromagnetic spectrum causes the problems right so we're working this region which is very safe more importantly from a very fundamental perspective which is the physics that tells us light occupies a very special region of the EM spectrum this is the


only part of the EM spectrum that allows us to probe molecules directly so we have access to the molecular information we know the importance of molecules in biomedicine right so we have to use a light and because light can probe molecules we can apply this to biomolecules all the biomolecules you can think of right you can read the four major classes of biomolecules some other endogenous or


intrinsic biomolecules or even exotic molecules you know later on I'm gonna make a point that in fact by using photoacoustic tomography week we can potentially image any molecules right so this can be extremely powerful by using by imaging biomolecules we can provide all sorts of imaging functionalities for example in vivo functional imaging very much like functional MRI you might have


heard of so x-ray will image structure very well but x-ray may not be able to tell if a piss piece of tissue is alive or dead right so we want to image not just the structure of the tissue but also the physiological function and photo acoustics or optical imaging in general can provide that type of information in vivo metabolic imaging so this is someone like PET imaging


positron emission tomography you know we're looking at metabolic parameters right so I enumerated a couple of examples such as the metabolic rate of oxygen glucose consumption rate we all know that these are the two major mechanisms of metabolism your body right in vivo molecular imaging so we're able to image all sorts of biomarkers which can potentially be hallmarks of cancer


for example and we can image reporter genes that allows us to track gene expressions we can even provide label-free in vivo histological imaging as we know standard histology is invasive you know when you go to the hospital if physicians who we need to do a histology on you that means they have to exercise tissue out of you all right so that's invasive then they'll go through a


series of procedures and prepared a tissue before they can examine the tissue slices under microscope so the whole procedure is ex-vivo invasive and takes time can we move this technology and transform this to an in vivo situation where we can look at a tumor margin right as we know that a lot of cancer patients die because the cancer cannot be removed 100% so there's small residual of cancer


cells and that are left around right so then the cancer will grow back can we use our technology to demarcate and basically find the boundaries of the tumor and remove the cancer 100% so that's going to save lives there are many many reasons why optics is so powerful but we face challenges one of the challenges is called diffraction right in high school or middle school we


were taught that you can focus a light beam through a lens to a geometric point all right if you say that in a high school you get a full mark right but if you say that in college the professor may tell you you're wrong right so because light is a wave anyways cannot be focused to a point a geometric point right the ultimate size of the focal point depends on the


wavelength right in this graph if you do your best try to focus as sharply as possible make this angle alpha 90 degrees your focus eyes will become wavelengths over - right that's how small you can focus this is called the diffraction limit so waves water fracked this year three of our colleagues working in our field were awarded the Nobel Prize in Chemistry actually for


breaking through this limit so this limit has been come they can generate resolution smaller than the wavelength which is amazing achievement now we face even more challenges in penetration right our intuition tells us light will not penetrate through tissue because we can't even see through our own palm right so when we close our eyes our eyelids is going to block all the light


we can't even see the outside but you will actually see light right this is why some people when they sleep they have to wear blindfolds you have to wear blindfolds our eyelids are not dark enough they're not blocking enough light right so photons you know basically it's a quantum term for light photons will actually go through the eyelids and reach the retina and this is why even


when you close your eyes you will see some light where's the challenge if we want to penetrate penetrate tissue and get images 350 years ago microscopy was invented right that really revolutionized medicine or any previous before that point there was no technology that allows us to see cells with the Y field optical microscopy we can see cells now we're at micron


resolution however you have to cut the tissue into very thin slices like ten microns in thickness and this is still the standard technique for histology or standard pathology analysis so what I call the penetration limit in this case is the operation right so the way from distortion in order to form a very good image you have to have a very regular wavefront


you have you have a controlled wavefront so in tissue because of the distribution of the refractive index in other words the speed of light will travel this light will travel at different speeds of light depending on which part of the tissue lion is traveling through and that gives you a problem that's gonna cause distortion and preventing us from forming a good image right so that


problem was overcome about maybe 20 years ago using modern optical microscopy you might have heard of a confocal microscopy two-photon microscopy or even optical coherence tomography these are really modern wonders of optical imaging technologies those technologies will reject multiple scattered photons they'll retain the on scattered or singly back scattered


photons for imaging and there was sharpen up the images they overcome this operation limit in penetrate from the original limit of say a hundred microns to about a millimeter by the way 100 microns is roughly the diameter of our hair that's how small it is a millimeter you can picture if you have a little ruler you can picture a millimeter right so a millimeter doesn't sound very big


but it's a huge advancement from 0.1 millimeters so 100 microns is 1/10 of a millimeter so that's a factor of 10 enhancement in terms of penetration right though those technologies have impacted biomedicine enormously right not just for biology but they've also been used in medicine if you go to your ophthalmologist one day they may actually use Oct article coners


tomography to examine the retina for you right because without Oct you can only see the surface of the retina you can't go beyond the retina there might be something going wrong sometimes it's behind the surface of the retina OCT is able to see through the entire resume layer very very powerful technique however this set of modern optical microscopy techniques face the next


challenge something I call diffusion limit right so they cannot go beyond one millimeter in depth in valid or tissue how do we overcome that problem so we use photo equipment rasca viewer in general photoacoustic tomography to overcome this problem where we actually use multiple scatter photons so I have a little cartoon here conventional microscopy use straight


propagating photons the modern optical microscopy will tolerate a little bit of a scattering because they can be checked multiple scattered light but to go deeper we have only multiple to scatter light left so you cannot afford to reject multiple to scatter light otherwise you will get no signal so we have to use those tortuous paths for our light propagation and somehow we have to


get spatial information right so that's the huge challenge because oftentimes when photons wander around through this tortuous path you'll lose spatial information so that means you're not gonna get a sharper image we somehow have to form a sharp image our solution is to use photo acoustics and as a result we advanced the penetration not just by one order magnitude by more than


one order magnitude more than almost two orders of magnitude now we're able to penetrate multiple millimeters even multiple centimeters so you're talking about not only skin level penetration but also organ level penetration I'll show you some more examples later like anything else we face the next challenge right we cannot penetrate beyond right now seven centimeters how do we target


the next challenge this this limit is called the dissipation limit because beyond this steps even the multiple scatter photons are spread around so they're not very intense even though you have a lot of photons at that kind of depth so the next natural question is can we gather those photons they make them intense okay so there's upcoming technique called the wave from engineering with


the internal guy stars there's hope there there's hope that we can potentially break through this dissipation limit and reach the next level this could be extremely exciting if we reach there because now we're talking about tens of centimeters of penetration by using safe light now we're talking about potentially whole body human imaging using known as a radiation with rich contrast information


so very very exciting I'll touch upon this topic later on and this is ability to time reversal now of course the ultimate limit is the absorption limit if you take all the scattering centers away out of the body you all you have left is absorption right so that's gonna limit your light penetration likely if you use the right light wavelength the right light color that penetration is


extremely long it's like a meter or so right all right so let's take a step back and ask yourself the question what does it take to get a good image if you we all know how x-ray chest x-ray works right chest x-ray works so well because x-ray does not scatter so much in tissue you get what's called ballistic light ballistic photons in x-ray regime so that's gonna cast a shadow directly for


you and you can see that the bones and certain structures if you mimic x-ray projection by using light when you have certain tissue thickness you're not gonna see see a shadow at all right because light will follow a highly tortuous photon path before reaching your observer right so on this side you won't see a shadow if we surgically cut open a tissue right that's invasive of course now the


right hand side is well very well defined because this is all exposed to your error in the photon path will be well-defined allowing us for two form a very good image despite the torch was fallen paths on the left side so the point I want to make is you only need one sided clarity you don't need both illumination clarity and detaching clarity well this is so invasive it's


not very useful right a better idea is called optical clearing so we can introduce certain chemicals into the tissue that's going to turn a tissue transparent right so that's going to achieve the equivalent to case P giving us a very sharp image unfortunately this process is toxic so you may have turned a tissue transparent but this is gonna kill the tissue so it's not very useful


for you vivo imaging what we are doing is to convert light or photons into ultrasound signals so we're talking about acoustic signals here through the photo acoustic effect acoustic scattering is orders of magnitude like a thousand times weaker than optical scattering equivalently on the detection side we've reached case P or KC without invasiveness or toxicity so on the


detection site now we're dealing with transparency that allows us to form a sharper image so that's the basic idea behind this technology right let's see I'll give you more demonstrations later on to make sure we understand the concept photoacoustic very much like x-ray CT there's also photoacoustic CT we have different geometries I'm going to talk about circular geometry first photo


acoustics as a physical phenomenon has been around for over 100 years in fact Alexander Graham Bell first reported photo acoustics he actually invented the concept of photo phone right very interestingly this paper was published only a few years after the first telephone was built he had a site you're building a photo phone using light to communicate so his idea was to


encode the voice or music into a lie beam then propagate a lie beam in space convert light back into sound again you cannot you hear that so he had no access to laser at a time that he was way be the head of the time you know because laser was invented in the 50s right so he had to use sunlight to demonstrate this principle now this idea never quite took off right for reasons you can


imagine because together to work you have to have a line of sight communication right but nowadays we have laser this idea may actually take off again with someone you actually revive this idea later for secure communication we have the opposite problem 100 years ago right so telephone allows you to talk between neighborhoods you know without worrying about line-of-sight


transmission but now we're worrying about security so between towers for example you know you have directed communication you don't have to you don't have to worry about you know losing your message right for security purposes so of course in those days there was no concept of tomography right that was not you mean in the lexicon it's a totally new modern concept we're


using this very old physics with a very new modern imaging concept to form a new imaging modality a very simple analogy I can think of for photoacoustic CT is how can we pinpoint a single sound source single point sound source like a thunderbolt so when we see the lining we can reset our stopwatch that would be our time zero when we hear the sounder we can record a time delay t1 multiply


the time delay by the speed of sound we will define radius first ergo shell on which lining took place if we have three such measurements Center at different locations we will have three spherical shells the intersection of the three shells will pinpoint the thunderbolt right so photoacoustic CT in essence is a straightforward as this its triangulation right something we learned


in middle school or high school right you can triangulate geometrically you can figure out the source right except in a real situation we don't have a point source we're gonna use light to generate a volumetric 3d complex source we don't know the exact source distribution because the source distribution is the image we're after so we have to use more than three detectors


but this gives you the basic concept at the simplest level so for photoacoustic CT the first thing we do is to expand the laser beam very different from a common use of laser where you want to use a very high intensity to drill a piece of metal for example so when we talk about laser you say well that would be dangerous you know this is a laser beam here I want to have high


collimation this is not very high power so the first thing we have to guarantee is safety what we do is to broaden the laser beam make sure the light intensity is within the safety limit so there's this institute called ANSI that regulates the safety of laser use if you stay within the safely safety element you're very very safe light will be scattered around so if you want to image


deep you have to tolerate light scattering we actually allow photons to scatter so you can penetrate multiple millimeters even multiple centimeters in biological tissue when light is absorbed it generates some heating we use very short laser pulses nanosecond right one nanosecond is a 1 1 billionth of a second right very very short laser pulses so this heating is very very rapid and we


don't need a lot of heating milli degrees right so one one thousandth of a degree would be adequate that will give you a detectable signal already so if you generate hundred hundreds of milli henries of million agrees then you have a very good signal to work with that allows you to form a bright image so this transiting allows us to generate ultrasonic emission is going to generate


Christic wave through the photo acoustic effect okay so this is the bells effect and because of the acoustic transparency we can detect all the acoustic signals and form a very sharp image outside however the contrast comes from optical absorption so we're combining optical contrast without drisana krez Ellucian these one common question is why don't we use ultrasound tomography why do you


have to use photo acoustics so you notice on tomography as you know you actually fire ultrasound pulse into tissue then listen to the echoes right so medical ultrasound imaging originated from sauna of sonar right so after the Second World War scientists and physicians started to borrow that technique in a pointer for a human imaging so what ultrasound imaging


does not provide is the optical contrast we want to have the optical mechanism as the contrast so we have access to molecular level information for example using light later I'm going to show you we can see the color differences of the two forms of blood oxygenated blood and deoxygenated blood red versus blue our veins you know look blue right the arteries will look red so ultrasound


will not be able to tell the difference that's just one example this is the first set of functional photoacoustic images it's also the first set of in vivo images acquired using photo acoustic CT this was reported in 2003 by our lab and we can see actually brain activation if he we go one side of the whiskers of assam animal and the contralateral side of the brain would be hemodynamically


activated so the blood flow will change and we can detect that change to show the brain activation on one side and those images were acquired now evasively so this work really started the growth of our field you know if you look at after 2003 our field really doubled roughly every three years in size after 2010 the conference on this topic became the largest in photonics West which is a


twenty thousand attendee gathering right so this has surpassed a lot of the competing technologies or you know peer technologies a natural question is why is this technology so exciting well this is probably the only technology that allows us to image from organelles all the way to organs in vivo and we use the same contrast right so we use the optic absorption as the contrast mechanism so


I'm plotting different implementations of this technology right we actually have far more than that can pot here but this says this is a highly scalable technology we can image at very much microscopic level but we can also scale to the macroscopic level this type of multi scale imaging can be very very important because in current medical practice or biomedical practice for


cells and below we use optical microscopy so we're acquiring optical contrast but for tissues and above we switched to now optics we're gonna use MRI ultrasound x-ray CT what have you so we're talking about two different contrast mechanisms mechanisms preventing us from correlating images across all the lens skills as we know to understand about the problem we have to have a multiscale


understanding you have to correlate information across the learn skills so photo tomography can potentially allows us to do so by enabling multi scale biological research and enabling translation of microscopic discovery to macroscopic clinical practice at least accelerate the pace of such translation so for the 2003 work we actually use a single element transducer that took like


20 minutes to get a 2d image now we have ultrasone arrays with 512 elements within 2 seconds so we can get a 2d image in fact now in our lab we're building a system that allows us to get an image within one millisecond so the technology is really getting faster and faster in terms of data acquisition so we can image the whole body of its Manimal right without without injecting


any contrast agents we can see the internal organs we've got 10 defined boundaries detect tumors detect functions the farmers are very interested in in this type of technology because what is the alternative to see this type of contrast they have to use x-ray CT the radiation dose is a big problem to monitor the same animal for development of a new drug you have to monitor the animal


multiple time points over a time course of a couple months at least so the radiation dose can kill the animal and it doesn't give you enough information as well because x-rays sometimes does not provide enough information right you have to have the functional information to make your to test the efficacy of the drug further acoustic tomography is simultaneously analogous to MRI in


pet so this is one example on this site we can see the hemodynamic contrast right so this is the concentration of hemoglobin we detect the brain again in response to electric stimulation of the pause of the animal on one side you can see the counter lateral side of the brain activate so on this side we're showing why this is analogous to PET imaging so we're using a glucose analog


that mimics glucose so when there's glucose uptake you can see stronger signals right this is very much like PET imaging so this can be potentially very powerful in the future as well because photo acoustics can serve as a backbone to connect with other standard modalities like MRI and PET we're trying to push bring image into the ultimate level human brain imaging this is extremely


challenging problem because human skull is a lot thicker than animal skull so that causes problems because the skull has a different speed of sound and soft tissue so this is like a photograph of the x-ray CT image X X we go a tall skull and this is a photograph and we put this k9 brain inside this skull which are the image using photo acoustic tomography actually some of the


colleagues predicted this will not be possible because the skull is so thick we got very very encouraging data so we got a image that shows certain structures which match the structures in the photograph very well the next big step is to push this to in vivo imaging of human brain unlike x-ray CT which always works in transmission mode because x-ray doesn't scatter much further acoustic waves


propagate essentially in all directions so that means we're very flexible in terms of actually implementation I just talked about the circular geometry for detection but we can also do it using a linear geometry so this is a hand hold ultrasound probe that you might have seen the hospital we have like hundreds of ultrasound detectors along this probe we use optical fibers optical fiber


bundles to deliver light with a single laser shot we can illuminate a volume below this linear probe it allows us to form a two-dimensional image so all the data will be acquired within say 100 microseconds so your boy motion artifacts when you acquire this type of images and you can see this is actually a standard ultrasound machine we worked in cooperation with Philips to modify this


clinic ultrasound system for concurrent photoacoustic imaging yogic dual contrasts for the acoustic contrast in ultrasonic contrast so this system works around this point allows you to penetrate multiple centimeters and get hundreds of microns resolution this is a one example where we can see a tiny absorber buried at a depth of five centimeters right this was not possible


using standard optical imaging right at this type of resolution in fact this is a form of reporter gene imaging or a form of molecular imaging again three colleagues receive the Nobel Prize in 2008 for their discovery of force and proteins you might have heard of you know this is a huge discovery that allows us to follow gene expressions but it's all fluorescence based by using


standard optical imaging you cannot penetrate these so all of the applications are limited to cells or animals at a very shallow depth now we're talking about multiple centimeters of penetration for this type of imaging so this is going to extend the capability of fluorescent proteins and some of the derivatives this technology is being tested at Washington University


for a human studies for human applications and this is one example where a breast tumor was imaged using standard ultrasound imaging and photoacoustic imaging we can see the CM tumor using a very safe light dose the laser intensity is one-half of the safety limit and a safety light safety limit is less than one-tenth of the dams threshold so this is extremely safe level light those we're


also targeting something that might have a more immediate application which is breast cancer staging you might have heard that the standard breast cancer staging is invasive you have to surgically remove the first draining node or the central nerve node what we want to do is to inject organic dye near the tumor it's gonna flow toward a central enough node then we use the


photo acoustics to detect us in the lymph node and use a needle which is guided by the photo acoustic technology to take cells out of the simple nerves node do you test if there's any presence of cancer cells so once this is a proven we can convert the surgical surgical procedure into a needle biopsy procedure this is some of the initial test results in humans you can see the central nodes


note we can see the needle here at as well in there another clinical problem is to monitor the brain oxygen consumption in the surgery you want to do it in the war but there's no non-invasive technique allows us to do that well so the current technique is invasive you have to insert into the carotid artery and jugular vein some sensors to detect the oxygen content so


can we do this now you massively we can use photo cosec tomography to quantify the oxygen saturation we use so2 to represent the oxygen saturation level at both the caudate artery in the jugular vein and you'll see that they have different values the difference in so2 tells you how much oxygen has been extracted by the brain so this is an indicator that tells you how well our


brain is consuming the oxygen if this difference is too small that means the patient is not consuming enough oxygen are you going to do something about it otherwise the patient might wake up from the surgery bring that so we've tested seven healthy volunteers that reach so2 is very similar to the expected range so this is very good news for us as a initial test the next


natural step is to move this into the war to work on real patients let me move on to the microscopy domain unlike the photoacoustic CT you will have to use math to form an image you know you have hundreds of sensors that Christic sensors you get all the signals then you send the data to a computer use your algorithm to form a image someone like x-ray CT image reconstruction but it's


actually more sophisticated because it deals with extra dimension so here we're gonna use acoustical lens very much too like lenses like I'm wearing a pair of lenses and everybody has a pair of lenses Eve even if you don't wear glasses right our eyeballs actually have lenses inside as well these are biologically made so here we're gonna use the acoustic version of


lenses to firmly image it directly let's just assume there's a target you know a piece of tissue we want an image we fire a light pulse to illuminate the tissue to generate photo acoustic waves and then we use this focused ultrasound transducer to receive the signals and you're gonna get a time trace like this so this is your time axis you get a voltage like this you'll see a spike


corresponding to where the target is so if this guide is deeper then this spike is gonna appear later if you have multiple absorbers or targets you'll see multiple spikes because we know the speed of sound in tissue we can convert this time of arrival into depth so this time trace is essentially a one dimensional image we call that a scan right or 1d image if we scan the system


across the Tish we got a 2d image you would call that be Skinner right now if you're Astros game on a tissue surface you got a 3d image so that's the basic concept and this is the detail now maybe I should skip this is this photograph shows the first 3d photo microscope which we published in 2005 so this is used to implement the idea I just described right so we focus light into tissue


right to penetrate deep beyond like a millimeter which is the limit how far how well we can focus right beyond a millimeter you can't really focus so well and so we use this what's called a dark field we use a done' beam on a surface to minimize the surface interference and then the ultrasound transducer is comfo wholly located you just want to maximize your signal


strength with a single laser shot you get a 1d image in the depths duration so this head is raster scan XY scan in its water tray to get a 3d image so this is the map rates around this point it penetrates three millimeters we can scale to a few more millimeters if we won't add expensive resolution everybody you can get tens of microns resolution so the resolution is getting better this


is an image of our own skin in this area of the palm there you can see blood vessels without injecting any contrast agents if you want to get the same type of images use x-ray you have to inject iodine base contrast or some other heavy metal phase contrast even then you'll miss some of the smaller vessels because x-ray does not give you enough contrast for vessel imaging so we all know the


importance of blood vessels this is a depth result or be scanned image showing you some of the standard skin structures now we're working with our dermatology department you apply this technology for melanoma imaging we've also miniaturized the probe so we can use this technology in the GI tract all right so you have to make the device tiny in order to be inserted into the


standard endoscope so unlike standard endoscopy like colonoscopy for example which only detects the surface of the lumen or the colon right so here we want to image beyond the surface these standard colonoscopy or upper GI endoscopy will miss anything beyond the surface we want to see deeper right seven millimeters is sufficiently deep in terms of the GI wall right so that


allows us to see the deeper structures by providing both photo acoustic and ultrasonic contrast mechanisms so this technology has been licensed to a large company for human translational commercialization I'll skip some of the details on the engineering side and this is by the way this is the first photo Costa endoscope we can also implement a photo acoustic microscopy at even finer


resolution so if we sacrifice the penetration now we're back within one millimeter penetration these we do want to cover the very top layer of the of the thickness so you can focus light more tightly that allows you to get finer resolution and you do have to somehow collect the ultrasound wave so we have to engineer this transducer or beam combine or what we call light some


combiner that allows us to combine the light optical axis and acoustic axis make them coaxial right so with a single laser shot you get an image 1d image and then you can raster scan to get a 3d image so this technology works around this point right so your penetration is about one point two millimeters but you're getting a single-digit micron resolution so this is one example where you can


monitor the same animal over time so this is angiogenesis meaning new growth of blood vessels right so we can monitor this process because angiogenesis is a hallmark of cancer cancer cannot grow without growing more blood vessels so it's a very important process of cancer growth and of course this is just the one side of the story the flip side of the story is we can potentially we're


actually doing that we're using the same technology to monitor drug the targets angiogenesis so we can use this as a therapeutic technology now therapeutic you use the anti-angiogenic drug to treat into genesis and we can monitor the efficacy of the drug this is another example we can see essentially every single blood vessel in the skin including the smallest capillaries you


can see here these are capillary pads you know the lines are single capillaries that are actually single of ourselves so we're looking at single cell lab already using this technology without injecting any contrast agents this is all what we coin dodged in this contrast we can also detect the color you know because our C and D arcy hemoglobin molecules have different


colors right so we can quantify the concentrations of both forms from which we can compute their oxygen saturation of hemoglobin right this is a very important parameter and we can detect arteries and veins by looking at the colors and this is actually coming out of our finger cuticle so we can image a human capillary loops and watch the color of the blood vessels and that


tells you where oxygen is released the most it turned out at the tip of the capillary loop seems to release most of the oxygen right so this is very interesting physiology in one day we can potentially use this to monitor some of the diseases involved in in human capillary level even some of the diabetic applications we're trying to push this photoacoustic oximetry to the


ultimate level right this is the device working at 1 Hertz just for demonstration purposes this is 20 Hertz and we actually work at 200 Hertz at this rate we can see single red blood cells traveling right so you can resolve single red blood cells in real time in vivo and watch how red blood cells bifurcate at this Junction we can also look at the color of each red blood cell


and look at how oxygen is released from red blood cells as we know red blood cells are oxygen carriers so this is the ultimate level oximetry it allows us to study some of the fundamental biology related to oxygen delivery and of course this is very much relevant to to cancer metabolism now this is very recent the data is unpublished as we know cancer primary tumor will not normally kill


patients is the metastasis that kills the patients so when the primary tumor somehow transported to a distant site that grows a new tumor and a grow to grow everywhere that kills the patient so CTC or circulating tumor cells are very important because this is one mechanism where cancer cells spread now we're able to monitor you'll see these flashes of white ash these are


circulating tumor cells if we can man identify them in the bloodstream right you can do multiple things to stop the metastasis right you could well you can imagine that potentially you can simply zap there's circulating tumor cells using a higher energy laser pulse that would be a Wang approach there are certain other pharmaceutical approaches you can think of I talked about


histology right so how can we make standard histology now invasive in vivo and we can actually detect the cell nuclei directly by using photo cosa microscopy we get an image that looks almost like standard HD staining histology so this is the standard histology this is the same piece of tissue that we acquired using our native contrast we use the optical contrast so


we can potentially move this into the o.r and find out brain tumor margin for example right so that can potentially improve patient survival we also try to beat that wavelength limit for resolution so you can see here this is the stander microscopy at a very fine resolution already but we improve that further to a resolution of 19 an au meters so this is sometimes called super


resolution imaging we break through this wave lens however to limit for resolution now we're detecting mitochondrion we can see some of the internal structures of a single metal counterion so now we're talking about this regime of resolution so so far I've demonstrated the scalability of photoacoustic tomography has applications in animals cells all the way to humans but we're also working on


time reversal because eventually wanna beat the penetration limit the photo acoustic tomography go even beyond what's available right now so time reversal is possibly one solution this is a very very interesting concept you know the we are actually inspired by astronomy the astronomers started something very similar because they want to observe the stars clearly


but our atmosphere is going to distort the wave coming onto the earth so that allows actually pours the images what they do is the fire a laser beam to generate some sparks the sparks in the sky will serve as a guide star there is its artificial Chi star it allows us to correct the wavefront distortion as a result you can form a sharp image like this so it's very striking difference


all right can we do the same thing in biological tissue right so we don't have first of all we don't have a guys there how do we solve that problem in biological tissue well let me illustrate the time reversal concept using this cartoon let's say we have a tiger this there's a bottle of liquid right that's gonna cause way front distortion so if you have plane wave way from very nice


way from on this side as a propagates through this bottle it becomes this wavy way from right this wave wave wave away from if it's reflected by this standard mirror like the mirror you use every morning it's gonna cause basically return its way from it'll stay wavy and when you go through this bottle again it'll become even more wavy alright so the conventional mirror is not gonna


give you anything that's reasonable it's not gonna give you a sharp image in fact you know by going through the bottle twice you get twice distorted you get an image that looks like a distorted tiger but if you use this special mirror something called the face conjugating mirror that's going to return the way frown in assert in the same direction right so you notice here this way from


curvatures are complementary to the from here right but this phase conjugate mirror is gonna return away from a in the same direction this is almost like a time reversal right the concept is like a time reversal you record some scene right if the person walks forward you play it backward the person is gonna walk backward so we want a wave we want an optical waves to walk backwards right


so that's why the phase can't you mirror does right when you go through the bottle the wavefront distortion is gonna be canceled through this bottle you get a very nice way from now you can see a very sharp image so that's the power of time reversal how do we implement the same concept in biological tissue we knew the guy star first of all to begin with which is really hard to do in


tissue in the early days our field actually embedded some molecules into tissue that provides it guys that are the trouble is that's invasive you have to poke the tissue to you eject some dye or floor force and it's also not very flexible because once you have that molecule in the location that's fixed you can only focus light to that position so what we do here is to focus


ultrasound to a given point and that ultrasound is going to attack light passing through the outside of tissue we detect attacked photons and time reverse the tagged photons back and it will come back to the outer assumed focal point so this technology is called time reversed ultrasound coded or true optical focusing in other technologies to use photo quistis as a guy star right so


this this is called optical speckle right if you have a camera embedded in a piece of tissue this is what you would see in general yeah you got bright spots everywhere there there are actually a lot of photons down there even when it's deep but they're all spread all over the place so using this optical focus we can actually collect a lot of the bright spots and concentrate them onto this


ultrasound focal spot if we were to use an your higher-order effect we catch you coalesce all of them into a single spot so this can be extremely powerful right so you here's the signal by 6000 times it's a huge enhancement one more possibility of finding a guy star is to use motion right so when there's blood flow freaks for example the blood flow can be used to serve as a guy starts


moving so we have this cartoon if you have a plane behind a child for example can we actually track that plane right so using the motion of the object as a guy star itself all right let me spend a couple more slides talk about one last technology we're working on in fact this paper up here today I knew actually this our work made cover of the nature as we know this is the best scientific journal


so we developed the technology that allows us to literally detect the fastest phenomenon possible right allowed by physics as we know Einstein's relativity theory says nothing can travel beyond the speed of light so we're detecting the light pulse itself and the light pulses are traveling in space at a speed of light we're capturing the light pulses as the light


propagates in space get reflected by this mirror and if the my rate bends as a crosses interface of two media you can see the angles will change right or you've had two pulses in two media and we can watch them a race and see which one will fly will travel faster and here you know what I saw a green pulse traveling here it'll excite some fluorescence and this red spot is


actually a fluorescent light so we're watching this fluorescent light to decay and with a single laser shot we observed this phenomenon even the force and decay is on the nanosecond scale because we have picosecond resolution so that nanosecond looks like eternity for us so this can be used for very high speed microscopy or you can potentially use this in combination with the Hubble


telescope for example to look at very large phenomenon right like supernovae for example so this has very broad applications potentially and this is the technology we just developed I don't know how much detail we need to get into this maybe I should skip at this late hour you can ask me questions later if you're curious about this so I've covered a lot of different technologies


here started with the motivation and challenges in your field I talked about photoacoustic CT photo QC microscopy in two forms time reversal and what we call cup compressed ultra-fast photography Washington University requires me to discuss my financial financial interest with two companies which have commercialized the photo because it photoacoustic tomography and


we're funded by NIH through various projects thank you very much I'll be happy to entertain any questions if there's any oh it's hard for me to see so tissue imaging is the main goal for our research but you can potentially use it for some other applications even non biomedical right you can imagine robotic vision for underwater right so photo if there's turbidity what we call when


there's a muddy water for example right you can't really see very far underwater so using photo acoustics so you can overcome the turbidity you fire some light pulses if your goal is to see a couple meters beyond you right so potentially like and propagate that for our generate acoustic waves then you can pick them pick that up and form an image does that answer your question


okay and there was yeah back there please so it hurt you a light-induced sound so what happens is light is first absorbed so you generate a transient heating a very short temperature rice right so on the order of nano second scale because we use nanosecond laser pulses and so that temperature rises as you can imagine is gonna cause thermo elastic expansion and that pushes tissue even


though this is very my new every milli degree gives you eight millibars or 800 Pascal's of pressure rice which is already detectable so if you generate hundreds of million degrees temperature rise then you get a very bright signal to detect and that allows us to form a image so this is called a photo acoustic effect so basically it's a photo thermal and thermal acoustic in the end that we


just call that photo acoustic affect the standard detectors has to be coupled acoustically to the tissue you can direct it touch it just like when you perform ultrasound imaging in the hospital they typically apply some gel on the skin to to ensure acoustic coupling water coupling is one way gel coupling is more convenient for a lot of applications however our field is also


developing non-contact sensing of acoustic waves through optical interferometry so if you shine light on to the tissue surface if there's vibration on the surface that displacement can be picked up through optical interferometry and that can be translated into acoustic wave as well so that's a potential non-contact version for now most of the implementations are


based on the contact version it's more traditional and it's better developed there's yeah please mm-hm so right now for breast cancer image in extra mammography is still the gold standard so we're still sticking with that one there are two types of directions that our field is taken one is to supplement extra mammography because x-ray mammography you know as


since it's as sensitive as it is they have trouble with young women with reader graphically dense breast so where they really feel miserable the other flaw with x-ray mammography is the very high false positive rate so that causes a lot of you know biopsies you know subsequent tests which turned out to be unnecessary eventually so can we use photo acoustics to supplement right if


x-ray detects this as positive can we confirm if this is truly positive or not by detecting the functional information another way that's more takes longer it's going to take longer to validate is to star from breast cancer screening to begin with so can we use photoacoustic tomography to screen for breast cancer without using ionizing radiation at all just start from from the functional


contrast provided by photo acoustics the reason I said is going to take longer it's because even though breast cancer is a huge problem the rate of incidence is still relatively low you know you have to test like a thousand patients to get enough patients with breast cancer so you can establish the statistics so it's a more difficult problem any more questions


yeah please all right images right yeah so it's a very good question your temp is still talking about photoacoustic tomography right so there are two different ways of getting an image with the microscopy technique with a single laser shot you get a 1d image which is depth resolved so you eliminate along the vertical axis for example then you generally the essentially a volumetric acoustic source


but then we use ultrasound transducer to pick up the signals so the acoustic time of rival is gonna tell you the depth information you get a 1d image with a single laser shot then you have to use scan linearly to get a 2d image then you have the if you want to get a 3d image then you have the raster scan that's one way of getting an image 3d image another way is to use a ray of transducers so


for example like the ringing array I showed right so we basically for the reign of 512 elements surrounding the head of animal or a body of animal or wherever we want an image like the breast then we use a broad field light illumination we don't focus light here at all we just light light photons basically bathe the tissue you generate the 3d volumetric source then your ring


is going to detect signals from a slice because we acoustically focus in the elevational direction the height direction and then we detect signal from the from this slice then we use image reconstruction to form a 2d image and if you want to get a third dimension of course you do the scan now this is a way the 1d array now if budget is not a problem then we can potentially get a 2d


array I mean in the ideal world that you imagine we could surround the brass or the head with a lot of transducers in that case with a single laser shot you should be able to get a 3d image but right now the the technology allows us to get a ring array or 1d array at a reasonable price but a two-dimensional array is I know quite expensive in fact the ultrasound world has been working on


that for quite some time and they're talking about one happy in other words one dimensional density is high the second dimensional density is much lower because you simply cannot have that many transducers ultrasound transducers and still maintain the cost yeah please mm-hmm so I I was trained in laser physics so I got my PhD from rice and I my PhD thesis was actually on my chemistry project


after I got my PhD I decided to switch to something more applied so I worked for MD Anderson Cancer Center there was a laser lab I think that was a very good fit for my career goal so for applications in ori i think there are several potential applications so one of them is the cancer demarcation as I mentioned can we have a complete removal tumor so you minimize the recurrence


rate another application as summation is the bring oxygen consumption monitoring we want to do that now you basically so this is what's so good about Wash U right so even though most of my lab spaces in the hilltop or Danforth campus I have a lab in the medical school as well we have a lot of collaborators you know so physicians Wash U physicians are very eager to work with engineers they


want to work with us the knock on my door come to my office want to work with engineers to apply our technology to their problems so we're targeting multiple problems it GI tract breast you know breast cancer staging melanoma you name it so we want to see the real impact in the human side the photo acoustic tomography has been commercialized by several companies now


I personally work with two of them so for preclinical imaging it has been you know established so there are products available they are being sold for a human imaging it's not there yet so I was not allowed to mention the name of the company which has licensed our IP for human imaging but so we're very happy that this is moving forward so it's going to take some time eventually I'd like to


John I believe a lot of things everything I believe I think is true but if I stop to think about it what do I mean by a belief what is the nature of belief yeah well I think as you know the mind is a biological phenomenon so belief is part of the biology of the mind and you won't understand belief unless you see it in relation to other parts of the biology of the mind now I

John Searle - What is Belief?


have to introduce an ugly word here intentionality and that sounds like it's a fancy thing it just means the capacity by which the mind represents objects and states of affairs so beliefs and hopes and fears and desires and love and hate and lust and discussion those are all intentional now that suggests they've got something to with intending but that's just an accident of history we

John Searle - What is Belief?


got this word from the Germans and like most of our confused words in philosophy I and in German intentionality doesn't sound like a position that's the word for intention so forget about the connection with intending and just think there is this capacity that the mind has to represent and it does that in a variety of ways and belief is one of the most important a belief in desire are

John Searle - What is Belief?


kind of matching concepts here because with belief we represent how things are or how we think they are and that has the mind to world direction of v am I supposed to fit the world but with desires we represent not how we think things are but how we want them to be and that desire has the world to mind direction of it the world is supposed to change to match the mind now how then

John Searle - What is Belief?


does all of this work as a totality all of these intentional States well I can't ask that question briefly it's too big a question but I can tell you some features beliefs are characteristically I justified beliefs required justification in a way that desires and hunches don't and beliefs are currently justified by their position within a network of other beliefs and other

John Searle - What is Belief?


intentional states and above all a network that contains perception so you see that the dog is in the living room and that is a kind of a boring belief but you come to the believing the dog is in the living room so you have beliefs that are both related to your perceptions and also many of your beliefs are derived related to other beliefs I believe that Barack Obama is active in the government

John Searle - What is Belief?


because I also believe he's president the United States but now the remarkable thing is that with beliefs there's a peculiar rational constraint in that the belief is not only caused by perception which is often the case but the belief is itself subject to rational assessment depending on not just what you've seen but what you've read and what you know otherwise and what seems reasonable and

John Searle - What is Belief?


what evidence you have so now I have to introduce another piece of jargon the belief only exists in a big network of other beliefs and other mental states and one part of the network such as my belief were in the United States that only makes sense in relation to the whole network I'd have to believe the United States is a country that if it's on the surface of the earth and so on so

John Searle - What is Belief?


belief is not belief it looks like it's pretty simple on the surface truth I got this belief I believe I'm an American but in fact it's part of a vast network of intentionality and you can really only understand it by seeing how the network works and how its constrained by rationality and by perception are there different categories of beliefs such that the belief that you saw your dog in

John Searle - What is Belief?