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and i just want to say one thing to the.students.uh and uh what i'd like for you.students to know is that uh we will be.taking questions to the speaker.at the end of course you can put those.questions in the chat and we will try to.go through those if you have questions.about what the speaker has to say today.otherwise i'm going to hand this off to.professor o'brien to introduce our.distinguished lecturer for today.well i've been instructed to reduce it.down to 10 seconds but i have.i have maybe just about twice that.amount or three times that amount.to introduce matt um.i have to say it's truly an honor to.have professor matt o'donnell.as an illinois ece distinguished.colloquium speaker today.this this talk is also under the.auspices.of the distinguished lecture program of.the ieee ultrasonics and.electrics and frequency control society.i've been acquainted with match for.professionally and personally for about.four decades.he is a well recognized pioneer.and scholar at the national.international levels and has.had many significant contributions to.advanced biomedical.engineering this colloquium speaker.announcement recount the.the announcement recounts his academic.and industrial positions.as well as many well-deserved honors and.awards.i'll let you read the uh read those from.the.announcement i'm not going to repeat.them instead i encourage you to read and.aspire to them.what matt has and continues to uh.emerge what what matt has done and.continues to merge from is his.creativity.his productivity and his fundamental.observations that have changed the.landscape.of diagnostic ultrasound by any measure.i think you would.recognize if you start reading his early.work.middle work current work you realize he.is a world-class leader.a pioneer a scholar and and.well-recognized educator also as you're.going to learn from this talk today.so matt i would like to turn it over to.you and.welcome okay so i thank you very much.thank you very for inviting me to come.to illinois lunch today was great with.you.guys i enjoyed it uh very much.um and hopefully dinner tonight will be.even better.so.start please okay oh i'm sorry.i have to change the uh camera.i should have done that before i start.so.everybody gets in real time to see.what your zoom skills are.there we go okay.sorry i should have a joke while i'm.doing that but.i don't okay.so you should see me looking at you and.the slides everything okay.all right and also please anybody uh.mute.your uh uh your audio out there because.i know i always forget to mute my audio.when i'm listening to somebody so just.ask you to do that.so i'm going to do uh.a quick spin about where sonics.ultrasonics and photonics come together.this is an area which i've been.interested in for over 25 years.and it started as a little hobby and now.it consumes almost.all of our lab is looking for different.applications of bringing these two.technologies together.there are three areas which i'll show.you just as examples.of uh how you can leverage these two.tools to do some really interesting.stuff in.in biomedical engineering so the first.will be on.uh photo acoustic imaging uh which we.have here and that's where light.generates sound the second will be.laser ultrasound and also some photo.acoustics on.uh involved in that too but this is.laser ultrasound where light.detects sound so that's the essential.technology there.and the third is uh in the area where.sound.tickles light and so this will give you.an example from that which is optical.coherence elastography.where sound modulates life so let's get.into the first one photo acoustic.imaging.photo acoustic effect discovered by.alexander graham bell.yes the guy who invented the telephone.it was called the photophone.when he first found this and it's a.fairly.simple effect but has a major.consequences so consider this little.simple gaddankan experiment.look at you have a piece of something.mimicking a piece of tissue and inside.of it you're going to have an optical.absorber.but we're going to have an ultrasound.array that's going to detect the results.of an interaction the interaction.is we're going to bring in light but.unlike traditional.optical imaging where you spatially.confine the light.but have a cw illumination so it's.temporally broad.but spatially compact we do the inverse.we bring in light which is spatially.broad and in fact the diffusion of light.and tissue is to our benefit.because we want light to go everywhere.but it is temporally compact.and the reason for that is is that when.this light.propagates through uh the medium.anywhere that there are absorbers.you'll create a little heat pulse and.that heat pulse through thermal.expansion.creates a particle velocity which is a.pressure wave.and that pressure wave can be detected.by the ultrasound transducer.and is given by a wave equation i think.this is the only equation.today but anyway is that the left side.is a wave equation for the pressure and.the right size.is the source or drive term but that's.given by this little heat pulse.and that heat pulse though for the light.that's going in is determined by the.product of the local.optical absorption of the of the region.times the amount of light the fluence.that gets there.so what does that enable what that.allows you to do.is to make a picture where the.information.where the um imaging information comes.acoustically.but the contrast is optical okay.so the source of the contrast in the.image the strength of an acoustic pulse.like you get.whoops like you have right there is just.proportional to how much.is absorbed okay now.from an optical point of view this is.great because it gets over the diffusion.limit.you can go centimeters into tissue uh.because you don't have to maintain.optical coherence all you're caring.about.is light is the absorption and as long.as the pulse length.is uh sure long compared to any.diffusion spread that you will get as a.result of diffusion.then you'll have this compact uh.acoustic pulse coming out which is.easily realized.so it's a nice way to get around the.diffusion limit.but i'm an ultrasound guy as as bill.said and so we looked at this.this photo acoustics effect as a way to.bridge the worlds of optical.and ultrasound imaging and in fact.there's a sweet spot we think in this.region where you have.several centimeters of penetration to.have so typically.areas where you would use 10 15.megahertz ultrasound instead of two.or three megahertz ultrasound but you.have this region where you can combine.ultrasound with this photo acoustic.imaging so.the immediate question is why why would.you want to do that okay this is.integrated we call it pause.photo acoustic ultrasound the reason you.can do that.is you can bring the beautiful molecular.contrast.that has been developed for nearly a.hundred years in optics.into simple ultrasound and so contrast.agents which in traditional objects.are things like fluorophores we now make.contrast agents which are.absorbers specific absorbers and this is.just the potpourri.of different particles developed in our.lab other competitors lab.uh around the world and this is the.excitement about.the photo acoustics as an add-on to.ultrasound is bringing a true.molecular uh dimension uh to.a fairly simple technology ultrasound.this is just an example it's one of the.particles we have in uh.developed in our lab this is done.obviously.we're scanning out a w because we're.from washington but.um the idea uh here is this agent is.actually a combined ultrasound and photo.acoustic agent doesn't matter.what the point is is that with simple.ultrasound.you can bring now a molecular dimension.through this photoacoustic effect.so it's exciting to be able to do that.however.for this to be truly clinically viable.you have to bring it.in to uh the clinic in the same way that.you deliver.ultrasound uh to playing so that means.first of all you.require real-time frame rates for these.interleaved images you can't give up.anything in ultrasound to add this uh.molecular dimension the second is.is that co-effectiveness size.portability are very very important for.ultrasound.but in the early days of photo acoustics.they were not so the image i just showed.you on the previous slide.that was the laser that was used that's.a unit sharpie right there so you can.see that's the the pump laser the opo.the power supply.is a cooling system underneath which is.uh.cooling this guy now certainly you can.make it more compact than this.but nowhere near the level that you have.here which is where.ultrasound handheld systems go so this.is a major.uh limitation and this and the last.is is that having lasers coming in.different directions.uh uh into the body is fine but the way.in which we do ultrasound is through.handheld probes.and so doing things in real time with.handheld probes so that the.user can be seeing the images to guide.procedures or to do instantaneous.diagnosis.is if you're going to add this optical.dimension then it has to be seamlessly.integrated with the probe.so this is something which been a system.working on for.about a decade now which was to change.the way in which uh.photo acoustics is performed and that is.the traditional.systems to date have been to use an.ultrasound array but then.integrate a big laser which pumps out a.single optical pulse into the tissue.we substituted an approach which is a la.conda ultrasound which is.we're going to scan fast very very fast.we use.low light levels but scan very very fast.and it put a challenge into the optical.delivery system.but what it does is it dramatically.reduces uh the burden on the laser.so if you look at that laser that we um.i showed you that we use for those.original uh.images our first step in this evolution.was to replace it with this laser and.there's your unit sharpie here so this.is something you can hold in your hand.so there's a laser you can just hold in.your hand it functions at a single.wavelength 1053.it's a kilohertz pulse repetition rate.and about 2.2 millijoules about 100.times.lower pulse power than this guy.but again it's this delivery system and.fast scanning that we have to.to design to take advantage of this.technology to produce uh photo acoustic.images of the same quality.well just to show you i'm not going to.go through all the details how we put.that together.but you can do it with that kind of.technology this is just a simple.experiment that we did which.mimicked drug delivery guidance of drug.delivery whereas.is done traditionally with ultrasound.where you bring a needle into.and this is just a uh excised tissue.sample not in vivo.but you bring it in you then deliver an.agent.but the agent in ultrasound you can't.see.in photoacoustics you can see it why.because you can.label it molecularly okay so these are.these pauses images so.interleaving we're interleaving these.fast photo acoustic images.with ultrasound images in real time.where the.photo acoustics brings us molecular.information and the ultrasound brings us.anatomical and sometimes functional.information okay.now in the last few years we've evolved.that system one extra step and that is.to try to do spectroscopy.this big laser the reason why we use it.most labs use some equivalent of this.is because we can scan wavelengths and.get optical spectrum.through photo acoustic measurements.leverage this technology that we have.here this this um.dio palm solid state laser into a.tunable uh thai sapphire.uh laser um that's able to sweep.over uh near ir range which is.appropriate for.for biomedical applications but again at.these high rep rates but slightly lower.about half the.uh energy that we had for the single.wavelength but still a very efficient uh.approach and again.in this fast scanning uh motif so this.is the system we put together it's a.real-time.uh approach and i'll just show you some.images but before i do that i want to.mention two effects.quickly which um have.limited spectroscopic measurements in.vivo.and the two major limitations for.spectroscopic measurements in vivo are.number one.tissue motion the reason being that.you must sweep through a range of.wavelengths.each wavelength takes a laser pulse so.to get a spectrum.at a pixel level to get a spectrum you.must go through multiple wavelengths.and so with the slower lasers that have.been used to date.that could take seconds to sweep through.there.and so just by movement of your tissue.you can.warp or or color spectra which have.nothing to do with molecular properties.or just due to motion.a second effect which can color a.spectra is fluence if you remember what.i said from the photoacoustic.equations is that heat generated is.proportional to the absorption.and the fluids and you really want the.absorption because that's the.fundamental molecular characteristics.however the fluence in tissue because of.this diffusion effect.the fluence can vary as a function of.wavelength.so depending where you are and make.photo acoustic measurements again you.can color that spectrum.because of the fluence variations with.wavelength which has nothing to do with.the molecular characteristics.of the object uh in which you're trying.to image.so those two big effects.this integrated photo acoustic ultra.uh ultrasound with spectroscopy.spectroscopic laser.by doing it fast and integrating this.delivery system.into it we're able to uh.i'm not gonna say solved yet we're able.to address.at this stage we're almost solving i'd.say we're able to address.these two challenges of tissue motion.and um.affluence variation so and so what we.can do is because we get these.these uh images still relatively fast.but still subject to motion we have.interleaved high frame rate ultrasound.pictures which we just used traditional.motion tracking speckle tracking for.your ultrasound folks.to re-register the photo acoustic images.and so we can eliminate the motion art.effect more importantly.though for any system no matter how fast.it goes.is that the fluence we can address the.fluence uh variations.through this uh fast scan approach.because we can illuminate the object.from different spatial positions.by having heterogeneity in spatial.positions.we can map the photo acoustic signal.changes with position.and from that of the same object okay of.a common object.that you map those uh variations those.variations can only be due.to fluence variations because it's the.same object.so you can compensate for them and.eliminate the uh the fluence variations.so that's the approach not only does.this fast scanning.allow us to integrate real-time photo.acoustic and ultrasound.but allows us to address two of the.major limitations to date.in doing in-vivo spectroscopic imaging.uh uh with photo acoustics.okay so let's just show you uh sort of.in simple fashion.how this works so this is exactly the.same sphere and i showed you before.but now i'm injecting an agent and with.the needle and all that.except when i scan through.i went through you guys saw it here.though i was sweeping wavelengths right.so it came along went boom.boom boom boom boom boom and what i was.doing is sweeping wavelengths as i was.going through that scan.so now i have images of my object.but at different wavelengths right.so if i can correct for the fluence and.correct.for the um motion.then i can look at the spectra at a.pixel level.now this was a stationary target so all.we did was fluence uh compensation.but when we do that we can look at.pixels and say these pixels here here.and here.have very similar spectra what are they.those spectra are matching to the.contrast agent.however when i look in other pixels.here for example which are those.associated with the needle.we get a fundamentally different.spectrum why well of course the needle.has different absorbers.than does our contrast agent so.here now is we can do a very simple.trick which is used in.you know all sort of systems people.elect in.ece do this stuff all the time you can.do projections right so you can.decompose.these signals do projections and so you.can make.images of the components and so that's.what we do.so we have just our raw photo acoustics.but this is the power of the.spectroscopy.the spectroscopy now allows us to.separate the components.so here and just this is sort of a.validation before we inject any gold.any of our agents we see nothing here we.only see the needle.then we start to inject while the.needle's still there we see both.we pull out the needle and of course all.we see left is the agent.okay so you can do that this is just a.simple demonstration but you can do that.for multiplicity of agents.because if you have a unique optical.spectrum.and you correct for fluence in motion.then you can you can capture that.this is in vivo test in a small animal.just showing you can see the motion.here's that scanning through wavelengths.uh like we did and so now you get these.images at different wavelengths.if you don't do any motion correction.you get this blurry image and you can't.match spectra well.when you correct for motion you can.match spectra in vivo almost perfectly.to the.contrast agent spectrum and you can get.very robust images showing exactly.concentrations of where that agent uh.is and we actually did a really crummy.job of delivery here.because we chose to try to get a region.in here but it was validated afterwards.and at least proved that technology of.being able to.do this in real time so that's a quick.flash through photo acoustics but this.is a piece about where you can use.light to generate sound and the primary.motivation for that.in biomedicine is for going that.molecular uh bringing a molecular.characteristic to the simple image and.modality.of ultrasound okay let's go to the.second one.laser ultrasound where light detects.sound.okay so let's let's do the same.experiment we just did before which was.uh a photo acoustics.so we're going to bring in a a a pulsed.laser radiation.but this time we're going to tune the.wavelength.to the material we're interested in such.that all of that energy.is absorbed within a few microns of the.surface.so we get a very very efficient transfer.of optical energy into acoustic energy.that launches an acoustic wave into the.material.and then we're going to reflections so.traditional ultrasound reflections.that come back we're going to detect.optically.now why would you want to do this both.optical generation detection.it's so that you have no contact so.there's.absolutely no contact whatsoever with.the material.this is important for a number of uh.different applications as i'll get into.in just a minute okay now.laser ultrasound's been around for.30-something uh.years um but its achilles heel.has been the detection sensitivity of.on the optical side it's typically three.orders or so.magnitude worse detection than your best.piezoelectric transducers.what we've developed over a period about.a decade now is some tricks.where we've done two things i'm not.going to go through this whole uh.spec interferometer but we did two.things.to uh uh overcome that um uh that.limitation of traditional optical.detection number one is we change the.interferometer type.to one that's called the sagnac.which gets rid of a reference arm so the.reference arm.of a traditional optical interferometer.will replace.with something which is a time delay.that is you have both.a true pulse or a sensing pulse and.a reference pulse are just time delayed.and reflect off the same.surface so the same surface acts as both.source.and reference okay which improves.efficiency greatly when you have uh.rough surfaces non-metallic types of.surfaces that's one trick the second.trick is is we use integrated optics i.know you guys at illinois.are big uh uh big leaders in in these.types of technologies.but we use integrated optics and.polarization maintaining.uh devices and a differential approach.and again afterwards anybody wants me to.talk through this i'd love to talk.through the details of this guy.but it's overcome about two and a half.orders of magnitude of the sensitivity.limits which means that.now we have something actually functions.like a pulse echo ultrasound.transducer but is entirely non-contact.um and for applications so here is.one application which is actually the.original motivation for the work this is.while i was still dean.and was giving an alumni tour through.boeing.and they uh have this problem that.the composite materials which are going.into the modern aircrafts like the.787 especially.are dramatically changing aerospace but.they have a problem the problem is.is they really don't know very well how.they damage so you just saw this yes you.did see that that truck just ran right.into the fuselage of that plane i'll let.it play again.bam okay you say oh that's so funny yeah.this happens once per year on average.with the worldwide fleet.okay now it may not be a truck maybe a.lightning strike.maybe something else but there is one.major collision.on average once for every aircraft in.the worldwide fleet.it's not what cleared to do okay that.truck guy hit there what do you do.if it was a metal aircraft you go up and.look because there's a very strong.correlation between the visual damage.and the damage inside that's not true.for composites.and so what boeing and when i took this.alumni group through i said oh oh.opportunity right so is there a way for.doing non-contact.fast ultrasound inspection on in sight.uh to look at damaging composites.so that's what we did so we used the.system built this system for that.so just for the non-ultrasound people.quickly.type of images i'm going to show are a.little unusual but a scan is just a.single one line just like a.radar or ultrasound one line which is.range.uh at one position.you then scan that position to get b.scan so you get cross-sectional images.but what i'm going to show you are c.scans which are you get a three.volumetric a data but i'm going to.present the images back to you.slice by slice by slice and you'll see a.movie.where you'll be looking from the front.surface of this part to the bottom.surface of the part okay.and this is just an example so here is.an impact damage on a composite sample.visual inspection is this little dot.right here in the middle.and we compared our uh low scanner which.took a few minutes to do this scan.versus three hours and many thousands of.dollars on a micro ct system in the in.uw.hospital that was interesting to write.on a grant.um for this and we're going to do a.comparison so i'll play the movie but.remember the movie is we're scanning.from.top to bottom of this uh sample.and so what you're seeing is the flaw of.the damage.and these are the propeller uh.delaminations.which are known and you can see here.almost identical.information you're getting from the uh.from the laser ultrasound and the ct.huge volume involved in that uh uh.damage um even though.surface inspection is like the size of a.a small marble or a.ball bearing okay so.looks pretty cool but i'm a bio guy.right i'm a bio engineer so.so that was cool that was fun you know.and you got to get alumni happy and.stuff like that but it was okay how do.we actually use this stuff and so in the.last.few years we've been looking at ways to.use this non-contact detection for.biomedicine.and so three we've pursued one is.label-free.flow cytometry that is not using any.fluorophores to do cell separations.in flow cytometry the second is to try.to do.uh point of care histology uh using.non-contact photo acoustics and the.third which i will show you a few slides.of because i think um.it's interesting i mean i think it's.it's a potentially real application.which is scatter-free spectrophotometry.okay.so what the hell does scatter-free.spectrophotometry mean well first of all.let's talk about what a.spectrophotometer is.many people use especially in the.biomedical sciences and the chemical.sciences.but the idea is pretty simple as i said.optics.goes into this molecular characteristics.of materials so a spectrophotometer is.normally used let's say this is a little.a godonkin thing again.i have my latest nanoparticle okay in.there and i want to know what's the.absorption spectrum of that nanoparticle.i put a solution of that nanoparticle in.a spectrophotometer which just has a.source and detector.and just measures the attenuation of.light along a fixed light path.and from that draws out what the.spectrum is what the absorption spectrum.is which is related to the molecular.characteristics.of this uh of the absorber or the.nanoparticle in this case.what happens though if you want to look.for those absorbers.inside of something complex so for.example.inside of live cells so.that by the way is our ultimate goal.doing spectrophotometry inside.of live cells so when you do that.put these uh nanoparticles well.yes there's absorption but there's a.hell of a lot of light scattering that.goes on here and so you can't.so you have a lot of attenuation which.may not be related to the absorption and.the.molecular characteristics themselves now.they're pure optical tricks.with integrating spheres and other.things.but they're very sample dependent and.and hard to calibrate we were looking at.a very very simple.uh uh approach in a very simple system.to be able to get optical spectra inside.of uh.living cells analogous to the way you.make a.measurements um in solutions.okay so here's the idea the idea is.we're going to make a photo acoustic.system very similar to what i talked.about in the first.bullet of this talk but we're going to.use the non-contact detector which i'm.talking about now in the second bullet.of this talk and we're going to unlike.what we did before.where we spread the light going in for.photo acoustics we're now going to focus.the light and so what we have is a.little microscope.but we have a photo acoustic microscope.but it's 100.non-contact and the idea is we're going.to scan this.to look at cells in cell culture.all right and so a little proof of.principle just of of this idea.is we first take uh and do scanning.in a sample which consists of uh free.nanorods and free cells.our pure spectrophotometry measurements.as we said are complicated because.you have a signal that you get just from.the cells themselves due to scattering.and the like.but uh uh this simple system.superposition is not too bad.so when you look at the uh.just the difference between these two.spectra it's pretty close to what the.true absorption spectrum is of the.nanoparticles that you're interested in.because the cells don't at these.wavelengths don't absorb very much.scatter a lot but don't absorb very much.so it's so it's not bad.however what happens when those.nanoparticles are endosotosed.into the cells so they're intimately.linked the.the uh nanoparticles in the cells and so.you can't separate.in this simple way you get these uv vis.spectra.if you subtracted them you get nonsense.you have nothing that has to do with the.spectrum.however when you do it photo.acoustically.and they're just else you get this one.when they're inside the cells you get.this red one.which is which is very interesting let's.look at that in the next slide.when you so the spectrophotometry.measurements are garbage they don't mean.anything in this complex environment we.know that.when they're outside the cells you get.this nice simple spectrum.when they're inside the cells you get.this split spectrum what is that.endosomal capture so we were able to.image endosomal capture of these.nanoparticles.because of the blue and red shift that.you have.because of the alignment we have a.particular type of nanosystem where the.alignment.uh changes plasma on a coupling and so.can change the resonance.and so we could see that and so that's.again our goal is to be able to make.these types of images.in live cells to see dynamic processes.while using uh.using a non-context spectrophotometer.non-contact photo acoustics as.spectrophotometry.okay flash and dash.so let's go to the third one.and the third one is where sound.modulized lights where sound.tickles light okay.and the technology is optical coherence.elastography.and let me give you a little bit of.motivation because we're buying well i'm.bioengineer.bill's a bioengineer michael's a.bioengineer so i've got a few.bioengineers here.but always we start with what's our.clinical motivation what's our bio.medical motivation and the motivation.for this.technology is to assess the mechanical.properties.of tissue types of these small big.tissues.without any contact okay.say where where would you do that well.one is the cornea and i'm gonna.do a lot of stuff with the corner so.i'll focus on that there's other places.like the skin.this is especially true for burns and uh.for any kind of grafting procedures is.you don't want to touch especially post.graft.you don't want to touch and the third is.very very delicate small.samples i'll show you work today from.cornea a little bit of skin.and i will have nothing to show here but.our ultimate goal there is to be able to.monitor.sort of uh longitudinally uh.development of tissue types in organ on.the chip.type of constructs okay.so let's go to the cornea and why do you.want to know the elastic properties of.the cornea well form follows function.and the function of the cornea of course.is the primary focusing.lens uh of your eye and its shape.right its shape that turns its focal.characteristics and the shape is.determined by the intraocular pressure.that is the fluid pressure that you have.inside your eye.trying to push the cornea out and.with the response coming from the.elasticity of the cornea.all right so the deformation uh so the.focal characteristics are determined by.this fundamentally biomechanical uh.effects.the clinical standard of care is they.measure shape and iop.and iop is done either with this contact.approach.i like to watch that play a while to see.how many people start to.have their sphincters tighten and and.worry about this this contact uh.in the eye you can either get that or an.air puff i usually get the contact one.but i'm pre.anesthetized when they uh do that that's.how you measure iop.and then of course uh optical imaging uh.to look at.shape um.so our goals was to get much much more.you know develop measurements uh for.both diagnostics and guiding therapies.as our goal is to quantitatively map.elastic modulus because all.iop measurements now assume a uniform.elastic modulus for all humans.all humans have the same elastic modulus.probably not true.so anyway we want to do that we try to.measure iop.independent of the corneal elasticity.this technology and finally is our.ultimate goal is to guide and optimize.the therapeutic interventions because we.uh as i'll show you we can do this.imaging in real time.so the idea is to try to guide uh.corneal transplant surgeries lasik.surgeries all these types of things.with this technology but today i'm only.because i only have about 10.12 minutes left i'm only going to talk.about uh quantitatively mapping uh.elastic modulus uh with this technology.okay so to map last.so this is elastography this is.something which is a.has boomed in uh ultrasound.in um magnetic resonance and now.starting to come into.uh to optics and the uh the idea is.is to do this kind of mechanical mapping.you need three components one you've got.to be able to image.the second is you've got to be able to.deform and the third is from that you.need to quantitate.to work backwards to solve inverse.problems in order to get the uh elastic.modulus so you need non-contact imaging.quantitative approach.and for this application non-contact.deformations because it has to be.totally non-contact.uh system well the non-contact.imaging was great we just went down the.hall to our friend ricky wong who's one.of the.leading experts in in um phase sensitive.optical coherence tomography.and so and fast scanning uh systems and.here.we can measure displacements down to the.nanometer scale with these obstacle uh.techniques again in in real time and so.we're leveraging that technology.and at the end when i show pictures of.people i'll show you ricky's group.because they've been the fun.fiery fun group uh to work with as they.have this technology.that we're using okay the second is.quantitation and this.is the concept of dynamic elastography.which is now.wow 25 years or more or old.where you use imaging systems.to track the propagation of shear waves.in tissue okay because in simple bulk.isotropic media that shear wave speed.is directly related to the shear modulus.in the simple way.and the young's modulus which determines.tissue deformations.in an isotropic uh material uh nearly.incompressible material like.tissue say liver is just three times.that value so.so from these wave speed measurements.you can directly get elastic modulate.which are going to tell you how things.are going to deform.which is of course what you want to know.for the cornea because it's this.mechanical.uh this mechanical organ okay.but the rub so that's you know exciting.cool.let's charge but the rub is we can't.touch anything.so how do we make a deformation if we.can't.touch anything so it's got to be totally.non-contact system.is required okay so we looked at a bunch.of things.the air puff which is used clinically.yeah it's non-contact but oh boy i don't.like i mean it makes pretty serious.uh deformations anybody had well i can't.see i can see bill and.michael but anybody had an air puff iop.measurement.okay not the nicest thing in the world.is it.so um in there so anyway but also from a.technical point of view even though it's.non-contact.it's very low frequencies you can't get.very high spatial resolution with them.it's very hard to direct them.and do that so we went back to one of.our.bag of tools and said oh let's do photo.acoustics we'll whap it.with a photo acoustic thing like a laser.ultrasound system and we time and space.modulate it so it's appropriately right.to launch away.and we did that with pulse uv light.because uv does not propagate into.the cornea very far problem was to get.sizeable waves we.we were near cooking the cornea so.that was not going to work so we kept on.coming back to you know but ultrasound's.been doing this for 20 something years.you just get ultrasound in there.but you need ultrasound to be coupled.into the tissue.to do this so one bright.post-doc at a group meeting one time.just said.why don't we just put it through the air.and of course after everybody stopped.laughing.and started talking and we realized well.why not.because actually propagating ultrasound.through air gives you almost a perfect.force transducer.because that ultrasound is perfectly.reflected because of the huge mechanical.impedance mismatch.between tissue and air and that gives.you a.very large radiation force the question.is.how do you get ultrasound and air to the.surface and shape it in time.and space in a way which can launch the.appropriate sized uh mechanical ways.well we did it we we designed a set of.error coupled.ultrasound training as you can see this.is uh one of the post doc actually the.postdoc.had the crazy idea we made him build the.transducer too um.it's just pushing around some salt uh on.the table just showing that.this is pretty powerful stuff uh if you.can get it through error coupled.well when you go through the numbers it.turns out.about one to two megahertz ultrasound.will propagate.anywhere from five to fifteen.millimeters in air.which is a piece of cake for uh.ophthalmology you can just keep it about.a centimeter off the surface is no.problem.and you can get more than enough sound.to that surface.to propagate micron scale mechanical.waves which are easily tracked.with oce so that's what we did so we.called this thing acoustic micro tapping.and so it takes air coupled ultrasound.and then we image in real time with a 4d.oct system that is three spatial.dimensions in real time.and you do experiments like this so you.hit at the surface.and if you have a bulk material you will.create two ways a surface wave or a.rayleigh wave propagating along the.surface.and a bulk shear wave coming off at a.fixed angle which is pretty.which is constant for all tissue because.it's nearly incompressible.and so you contract these things because.the speed of these things like we said.is directly related to.uh the elastic modulus and so there's a.little bit of a fudge factor if you use.the rayleigh wave versus the bulk wave.but there's just a simple.proportionality between those.okay so how do you make wave c estimates.well for example if you just looked.along one surface say the the top.surface.you can make plots of x t and just the.instantaneous slope.tells you what the speed is right.pretty straightforward so we built it.you stick it together we took one of.ricky systems.one of our air couple transducer systems.we stuck them uh together integrated.them together make it sound easy of.course it was a phd student in a postdoc.about six months of their lives to do it.but once it's all together uh.you can make pictures like this so this.is um.and i'm showing them at non-real-time.speeds it took one third of a second to.gather all of the information.that's shown in these movies what you're.looking at.is the gray scale now is not ultrasound.the gray scale is oct.and it's showing the cornea which.anatomically is not very interesting.other than what's looking at the apex.where you get a specular reflection.echo you ultrasound guys that's a.specular reflection.artifact that you get but it's optically.but.what the oce is we're mapping you're.looking at let me go back.i have the movies plug it here's what.you're looking at is the propagation of.these mechanical waves and we're looking.at the difference but this is an animal.model between 10 millimeters of mercury.and 40 millimeters of mercury.and of course it goes much faster right.oh.but i thought all humans were one.elastic modulus.even just iop is.part of the equation so you can map them.you can make pictures of them.it's all wonderful right you do it in.skin.we can see stuff in skin here's just.simple stuff we're looking at burn.patients now.we're starting to build a robotic system.to do this for.skin uh imaging 3d oct and oce.combined together.now but wait a minute give me a break is.it really this easy.no as you might expect right i mean i.tried to make it.like it was easy just so i could have.that loaded question so in the last.about five minutes or so.is there's more complications every time.it's like the classic onion powder.we just keep you know peeling the layer.of the onion and there's another layer.of uh complications and so i'm a native.new yorker if you haven't.couldn't tell by now um and so.complications to me has.problems problems problems i just.problems i have to.to solve well there's lots i'll just.give you two what you think are the.biggest ones.and show you this is one of the few.times in my career.where a problem slash bug turned into a.feature.okay so to show you that okay so the.first is.bounded waves okay so the cornea.is very thin it's about half a.millimeter in in humans.almost a millimeter uh in pigs but still.very very thin.and our acoustic wave wavelengths are on.the scale.they're anywhere from a few hundred.microns to to millimeter.so we're right in a true guided wave uh.situation.all right so when we had that simple.case again where it's a bulk material we.can do instantaneous derivatives to see.uh what the velocities and therefore the.moduli are when you do this bounded.oh my goodness that is a very.complicated wavefront and if you just.look at the top surface you get.something like this.okay and it doesn't make sense you can't.do simple derivatives and in fact people.have tried to do this.get artifactual images because you just.from the cuts and bumps that are in.these.interference patterns are infer they.infer it's you know.modulus changes has nothing to do with.that it's a guided wave behavior.okay but as good ees and physicists is.we know how to handle.uh complicated super imposed ways is we.look for modes and mode structures.and we did that in our case by looking.at two dimensional fourier transforms.and from that we can see distinct modes.which you would expect which are lam.wave modes.uh uh for acoustics people our classic.lamb wave modes.and we can do theoretical calculations.and match up with measurements and so by.doing dispersion analysis.we can get back to some quantitation.okay.so that's the first piece so it's.complications complications but it's now.you have to make sure that you have.sufficient bandwidth in your system to.do robust dispersion.uh analysis so that was the the first.complication which i've had to address.okay the second one has to do with.isotropy.so when you're looking at elastography.in the liver isotropy.is a very good uh approximation when.you're looking.at elastography in the cornea isotropy.as i'll show you.is not a good approximation so.in tissue types there's two basic forms.of mechanical testing that's done on.tissue one's a tensile test as is shown.here and that's directly related to.calculations of the young's modulus.okay and those types of measurements.made in excised.animal and even human cornea tell you.that the young's modulus of.cornea is in the megapascal range.the second type of test is rheometry or.shearing.tests you can make okay that's just.shown here you can see the little movie.how you can.shear the things and this is a measure.of the.direct measure of the shear modulus okay.but in the cornea when people make these.rheometry measurements which we have.done too.they're a little messy but you can do.them you see you're in the tens of.kilopascal.rain for the uh shear modulus.so is the cornea isotropic.well if it's isotropic and.incompressible and it is.incompressible or nearly incompressible.e should.equals three mu well in the human cornea.say about three megapascal is a.reasonable e mu is about 25 kilopascal.so three times you 75 well over an order.magnitude off.no way that the cornea is isotropic.so i just answered my own question.but that makes sense when you actually.look.you know micrographs of of the cornea.it's layered sheets of collagen.okay it's laid down in these layered.sheets.and it's much more uh appropriately uh.modeled as an anisotropic material in.fact.a transversely an isotropic material we.have put a sort of a variation on the.theme and what we call as a nitty.is it a nearly incompressible transverse.material.what that just says is that we assume.that the longitudinal waves or the.traditional ultrasound waves.are um uh isotropic.and that's not uh even if they're not.that's not a big it does.the errors that you make are very very.small but we do say.that these shear moduli now we have two.we have an in plane one.and we have an outer plane moduli.okay and so g is an additional.independent shear modulus like i said.you have one in plane one outer plane.all right for an incompressible material.e.does in fact equal three mu but it's.just mu.which is uh the one corresponding to the.vertical plane.and for torsional forces is determined.by the g so this this description.this uh uh nitty description captures.what's is the biomechanics of the cornea.so the question is is can we use oce.to get at g and mu together both of.these.okay so it allows us to decouple these.okay.so that was a good thing and then we got.the bad news.i seem to get the bad news at our weekly.group meetings i'm not sure i want to.keep going back to my weekly group.meetings but anyway we.we get them and said okay you know where.the postdocs did the did uh you know.theoretical did some simulations and.theory characters okay consider.you have a uh you know a infinite.half space of this knitting material.then you launch one of our waves what do.you see.but the speed of the wave is governed by.the square root of the g over row.okay has nothing to do with mu.so mu by the way governs the young's.modulus which is how it deforms so.therefore determines the shape primary.shape.of the the cornea and.we can't measure it we're screwed ah but.this is where a bug becomes a feature.i'll do this in two minutes and then.i'll quit where a bug becomes a feature.finally because the cornea is a bounded.material.this mixing of waves allows.a polaris because of reflections you can.have polarization changes in the shear.waves.which mix the waves which mix.information about mu and g.and so when you look at these dispersion.relations.and we normally have two modes that.we're most interested in.is they'll start to split based on.the ratio between these two moduli so.let me let's look at one more that.should have.got rid of those slides but anyway let's.just look at one mode so you can get the.feeling.is that when the you have isotropy that.is the two moduli.the same you have a fixed dispersion.relation but as that ratio changes.the shape and final asymptote of the.dispersion relation changes.so if you have a broad enough spectrum.to be able to map out precisely that.dispersion relation.then you can get these two moduli uh uh.independently okay as i just said.and can measure these fine so that's.what we've done here.we've done a quick measurement where the.top let me get the mouse up here.the top that's an isotropic uh phantom.we.built with pva it gives you these.interfering modes.you get the separate modes it works just.fine we look at the cornea we do not see.that kind of interfering mode because.now these modes are mixed.we see this simple mode when we fit it.to this proper.nitty model we can get the two moduli.and the moduli you're exactly in the.range of what you get for.um uh mechanical testing and we get.their non-linear characteristics as well.so a bug became a feature okay i could.see them at a time.so that's what i'm quitting so what i.tried to show you in a quick slap dash.uh run through some of this stuff is.some interesting ways to think where you.can bring light.and sound uh together for generating.light generating sound light detecting.sound.and light and sound tickling uh light.and hopefully.uh some applications that could be.interesting to you all.so i we thank the funding people the.people in red are faculty colleagues the.people in blue the postdocs.who have worked in the group uh the last.few years these are ours and.one of them are ricky and the ones on.top.i can tell you right now the sky in.seattle does not look like that.it is full of smoke um but anyway.that's uh i'll thank you and take.questions.and let me stop sharing so i'll change.the camera.well thank you very much matt i couldn't.help but uh.think of deja vu coming up because you.started your career.looking at the nature of uh collagen.and cardium right yeah now you're.looking at collagen.in the eye yeah 40 years later.yeah so it was interesting because um.like this air coupling thing.is when the postdoc said it is i started.to laugh and everybody looked at me like.you're not that's really not.the right you know you're supposed to.you were an old administrator you should.know better than doing stuff like that.but it was good it was in you know it.was all in fun and turns out it was.great.but the anisotropy stuff and the.collagen you know and linking to the car.that was you know me pushing to start.look this to start looking.at uh these things and it was it was.based on that history from 40 something.years ago right.and it's worked out it's it's worked.well.do you do you have a sense of what.parameter or parameters.or what kind of an image you would.provide to say the ophthalmologist.who's looking at the cornea yeah so.we're just starting out we have a great.uh md phd.collaborator ophthalmologist whose phd.by the way is in bioengineering.great um and uh.she says you know at first level is.that uh she wants to know sort of the.the.uh modulus in the apex region the.central region.of the cornea around it there.and then what she really wants to know.is because when she goes into.interventions is.okay how is it changing so we're trying.to think about.you know giving a more like a number.as a pre-procedure uh thing.which can then help you know a a model.say.okay how's you know if i make a cut here.how is it going to deform and make a cut.here.but then during the procedure to try to.do something differentially.so just look at and provide a delta.modulus image while they're uh doing.things so that's the thought.um we haven't done that but i mean.that's that's the thought.well i found it interesting is for their.um.pre uh pre-surgical planning.is really just a number was going to be.sufficient for them because.uh then if you have a good biomechanical.model you can say oh.i mean i if i take off you know 50.microns here or there then the model can.predict.and so they can go uh they can go with.that.so anyway that's what we're thinking.don't have a real answer yeah.interesting yeah thanks i think michael.has a question yeah there are a couple.of.there are a couple questions in the chat.one was for me but another one.from a student i think was how important.is the line width.of the optical source for obtaining good.photo acoustic.data the line what you mean the uh.line width in terms of uh um uh.optical line width i assume not spatial.line widths um but anyway.i'm assuming the optical line width is.it doesn't have to be it's it's we don't.need high spectral purity.so typically the type of sources we use.are.nanometer two nanometer uh kinds of.spectral purity.so um it's not that critical because.we're usually looking at.a few species simultaneously we're.trying to.um separate and their spectra are quite.different so deoxygenated blood versus.oxygenated blood spectra are quite.different.the contrast particles that we put in we.tune the spectra.right so we we can separate them in ways.things like now if you had high density.quantum dots which some people have.proposed for.for um uh contrast agents then you might.need some more spectral purity.uh uh in the in the laser but typically.you know a nanometer two nanometers is.is perfectly fine.uh a quick question about uh and one.megahertz in.an error yeah the attenuation is more.than 100 db per centimeter right so.what kind of levels do you need to index.but no all we have to do is kick the.thing so we get like a micron.scale displacements and so we've gone.from like a centimeter.off so we're trying to push to two.it's it's a fluid so it goes up.quadratically right so the the losses.are four times worse at two to narrow.one.right and that will probably have to be.within a couple millimeters.if we push up to two um the bandwidth.because again.trying to do this spectral stuff the.bandwidth is primarily determined by the.width.of the mechanical source that we create.so that how tight of focus we can.we can make and so we want to go up in.in frequency so that was the big.change where stuff started really.starting to play is when we had sort of.sloppy beams coming into we have.tightly focused couple few hundred.micron wide um.beams and i'd like to get down to about.100 micron.wide as a goal but to do that we'll have.to be within a couple millimeters.of the eye another question is how did.you manufacture the device that.integrates.laser into handheld probe in a.laboratory he's curious about the design.and manufacturing process.okay with great difficulty.um that that is a custom.uh design i mean you know a custom.device that we 3d printed uh onto a.uh onto the probe uh but we're working.with a big company.uh unnamed big company to try to uh.fully integrate that in a traditional uh.ultrasound probe.um and they're gonna be developing the.manufacturing process.uh for that okay.okay another question in your photo.acoustic system you scan the laser beam.across a sample.and recorded the acoustic signals is.there a reason why you.didn't just uniformly excite the laser.across the surface.that's the way you do it traditionally.but you need much more power.you need that's the part so you need.much more power which is really these.mega lasers.and uh by uh scanning it we can bring it.down because the fluence.at each fiber is conserved so if you.take a fiber bundle.and you come down the fluence in each.fiber is the same but with the big.lasers they all get it simultaneously.with the little one we get one at a time.all right.and so the difference is is because our.light is only on.one fiber at a time our laser source.goes way down.right so you have a big laser.running at low repetition rates or a.little with a lot of energy.or a little laser running at fast.repetition rates.and then to this trick of scanning will.give you equation it's not exactly.equivalent we lose a little bit but it's.a small it's a small loss that we have.by doing this with a tremendous gain of.the.of the reduction in the size and scope.of the laser.i think there's a question uh what other.dynamic cellular phenomena would you be.interested in in trying to detect with.these techniques.okay so the i'll answer that in terms of.the spectrophotometry.because that's uh photo acoustic spec.spectro optical spectroscopy in photo.photoacoustics.so what we're looking at the first.simple thing we're looking at.is uh trafficking of nanoparticles in.cell culture.and the idea is and and what the.inspiration for some of this stuff.was that um in photo thermal therapies.and some other photo um for the dynamic.therapies and others.is you do stuff and design things using.spectrophotometry you put them in the.body and they just don't work.at all and the reason is a lot of time.is that the agents change.okay and they change due to the way in.which they're either bound.to cells or whether the way they're in.the endocytosed.into cells and so that's what we're.looking at here.is the first test is looking at change.because we can do this longitudinally.it's not.real-time imaging but by cell culture.standards it's real time you know it.takes seconds to make the image but.that's perfectly fine time constant for.this.and so we can see how these particles.are trafficked.and how they change their.characteristics depending on the state.they're in.uh within tissue so that's one thing and.the second thing we're looking at.which we've done a little bit so you.know this is pie in the sky but i'll say.it anyway because it would be cool if we.can do it.is we're looking at uh far uv so like.253 nanometer that range so um.where you quadruple so you you know you.frequency double uh.a 1064 and then you double again right.so half of 532 whatever that is.um is in that range of uh.uv uh because we got nucleic acids.so the dominant absorber in cells at.those wavelengths is nucleic acids and.so.trying to look at subtle changes.um in uh uh nuclear.uh dna you know.uh this nucleic acid either.concentrations.or uh changes uh that you would have.uh in them uh like i said in this.semi-real-time.way when you're perturbing cells or.doing things in cell culture so.uh we've gotten uv photo acoustic.signals but we've not done the.experiment that i just said.uh and if anybody races out there to go.do that make damn sure that i'm at least.acknowledged if not a co-author.all right well it's after five and so we.need to let our speaker off the hook.here.just wanna say thank you and hopefully.everyone can you know.react and thank you thank you thank you.for inviting me so.i was gonna say this is that i always.enjoy going to uh.champagne urbana and this trip was one.of the top best ones i've had so far.so thank you for your information he was.going to.get here by way of las vegas yes.and i spent las vegas in exactly the.same place i'm spending champagne.urbana in a couple days i'm doing the.same in pittsburgh so.it's the way it is thank you very much.it's been.very energizing talk good.okay and for the students if you have.questions afterwards send me send me.notes and.you know i might be slow but i will.answer.okay thank you very much okay thank you.see y'all.you.

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There is a detailed instruction on how to fill up the form on the CAT website. Both written and a video format. The instructions are easy to follow. If you still find it difficult talk to a faculty if you are taking coaching in any institute or anyone known to you who has already filled the form.

Is Commissioned Corps military?

I really don't see the point in it. This is the era of Assymetrical Warfare... Small teams, special skills & training to go wherever and accomplish the mission. Our military and adjunct forces have enough on their plate. Paid security service providers (mercenaries) provide more boots on the ground but at a price. Unit cohesion, fire discipline, respect for the people and beliefs that we're with go a long way. This war as it is in South Central Asia has seen an increase in soldiers for hire unlike any conflict before it. I agree in part that the US should have a ready force of trained security p Continue Reading

What is the difference between a commissioned officer and a non commissioned officer?

One has a commission and the other doesn’t. Non commissioned officers are Lance corporal up to Warrant Officer class 1 (Regimental Sergeant Major). Commissioned officers are 2nd Lieutenant up to Field Marshall (5 star general).

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