Guide Star to Internal Medicine

This is one of those wow dealsthat science sometimes throws us. Combining the effects of ultrasound and light is used to produce anholographic image of any target area inside tissue.  However we read these results, the promise ishuge.  It is possible to produce a holographicimage of any part of one’s body with this. The tools still need to be designed properly but this is a revolution inimaging.

I do not know what thetheoretical limit of resolution will turn out to be but it is certainly waybetter than present practice.

Again practical devices willsurely come quickly as there is nothing in terms of technology here that gas tobe overcome.  So soon enough medicinewill be able to image a problem to a high level of accuracy and likely even acton it directly using a range of linked devices.

You may not have noticed, butmedicine is swiftly converging on a complete reliance on remote surgical toolsfor internal work.  This will accelerateit nicely.

A guide star lets scientists see deep into human tissue

February 11, 2011

A WUSTL scientist has invented the biomedical equivalent of theastronomers' guide star.To correct for atmospheric blurring, astronomerssometimes shine a laser into the sky near the spot where a telescope ispointing. The laser beam energizes sodium atoms naturally present above thestratosphere, producing a glowing artificial star called a guide star. Theastronomers use the ‘twinkling’ of this guide star to continuously compensatefor the effects of atmospheric turbulence on the light they are collecting fromnearby stars. The guide star thus allows astronomers to obtain much sharper,more detailed images free of atmospheric blurring. Shown here is a laser beamprojected into the night sky from the Keck-2 telescope on Mauna Kea, Hawaii.Credit: Paul Hirst/Creative Commons

Astronomers have a neat trick they sometimes use to compensate for theturbulence of the atmosphere that blurs images made by ground-based telescopes.They create an artificial star called a guide star and use its twinkling tocompensate for the atmospheric turbulence.

Lihong Wang, PhD, the Gene K. Beare Distinguished Professor ofBiomedical Engineering at Washington University in St. Louis, has invented aguide star for biomedical rather than celestial imaging, a breakthrough thatpromises game-changing improvements in biomedical imaging and light therapy.

Wang's guide star is an ultrasound beam that "tags" lightthat passes through it. When it emerges from the tissue, the tagged light,together with a reference beam, creates a hologram.

When a "reading beam" is then shown back through thehologram, it acts as a time-reversal mirror, creating light waves thatfollow their own paths backward through the tissue, coming to a focus at theirvirtual source, the spot where the ultrasound is focused.
The technique, called time-reversed ultrasonically encoded (TRUE)optical focusing, thus allows the scientist to focus light to a controllableposition within tissue.

Wang thinks TRUE will lead to more effective light imaging, sensing,manipulation and therapy, all of which could be a boon medical research,diagnostics, and therapeutics.

In photothermal therapy, for example, scientists have had troubledelivering enough photons to a tumor to heat and kill the cells. So they eitherhave to treat the tumor for a long time or use very strong light to get enoughphotons to the site, Wang says. But TRUE will allow them to focus light righton the tumor, ideally withoutlosing a single tagged photon to scattering.
In both cases photons take random paths through tissue. Some are lost(blue) but others (green) will reach the mirror on the other side of thetissue. The mirror is a special phase conjugate mirror that turns the lightaround and sends it back on its original path, as though time had beenreversed. Clever as this is, by itself it isn't very useful because the lightscatters again as is backtracks (left). In the new method, called TRUE,ultrasound is focused into the tissue (small black ring). Light passing throughthe ultrasound field is tagged by it and selectively returned by the mirror toits virtual source, the ultrasound focus (right). Instead of scattering, thelight is brought to a focus inside the tissue. Credit: Lihong Wang

"Focusing light into a scattering medium such as tissue hasbeen a dream for years and years, since the beginning of biomedicaloptics," Wang says. "We couldn't focus beyond say a millimeter, thewidth of a hair, and now you can focus wherever you wish without any invasivemeasure."

The new method was published in Nature Photonics, which appearedonline Jan. 16, and has since been spotlighted by Physics Today (both onlineand in print) and in a Nature Photonics Backstage Interview.

The problem

Light is in many ways the ideal form of electromagnetic radiation forimaging and treating biological tissues, but it suffers from an overwhelmingdrawback. Light photons ricochets off nonuniformities in tissue like a steelball ricochets off the bumpers of an old-fashioned pinball machine.

This scattering prevents you from seeing even a short distance throughtissue; you can't, for example, see the bones in your hand. Light of the rightcolor can penetrate several centimeters into biological tissue, but even withthe best current technology, it isn't possible to produce high-resolutionimages of objects more than a millimeter below the skin with light alone.

Ultrasound's advantages and drawbacks are in many ways complementary tothose of light. Ultrasound scattering is a thousand times weaker than opticalscattering.

Ultrasound reveals a tissue's density and compressibility, which areoften not very revealing. For example, the density of early-stage tumorsdoesn't differ that much from that of healthy tissue.

Ultrasound tagging

The TRUE technique overcomes these problems by combining for the firsttime two tricks of biomedical imaging science: ultrasound tagging and timereversal.

Wang had experimented with ultrasound tagging of light in 1994 when hewas working at the M.D. Anderson Cancer Center in Houston, Texas. In experiments using a tissue phantom(a model that mimics the opacity of tissue), he focused ultrasound into thephantom from above, and then probed the phantom with a laser beam from theside.

The laser light had only one frequency as itentered the tissue sample, but the ultrasound, which is a pressure wave,changed the tissue's density and the positions of its scattering centers. Lightpassing through the precise point where the ultrasound was focused acquireddifferent frequency components, a change that "tagged" these photonsfor further manipulation.


A conventional mirror (bottom) does not correct the distortion of awavefront produced by the water-filled bottle in this illustration. A timereversal, or phase conjugating, mirror (top), on the other hand, produces awavefront that precisely retraces the path of the light, as if time were goingbackward. It reverses the distortions introduced by the water, producing aperfect image of the tiger. Credit: Wikimedia Commons

By tuning a detector to these frequencies, it is possible to sortphotons arriving from one spot (the ultrasound focus) within the tissue and todiscard others that have bypassed the ultrasonic beam and carry no informationabout that spot. The tagged photons can then be used to paint an image of thetissue at the ultrasound focus.

Ultrasound modulation of light allowed Wang to make clearer images ofobjects in tissue phantoms than could be made with light alone. But thistechnology selects only photons that have traversed the ultrasound field andcannot focus light.

Time reversal

While Wang was working on ultrasound modulation of optical light, a labat the Langevin Institute in Parisled by Mathias Fink, was working on time reversal of sound waves.
No law of physics is violated if waves run backward instead of forward.So for every burst of sound (or light) that diverges from a source, there is intheory a set of waves that could precisely retrace the path of the sound backto the source.

To make this happen, however, you need a time-reversal mirror, a deviceto send the waves backward along exactly the same path by which they arrived.In Fink's experiments, the mirror consisted of a line of transducers thatdetected arriving sound and fed the signal to a computer.

Each transducer then played back its sound in reverse — in synchronywith the other transducers. This created what is called the conjugate of theoriginal wave, a copy of the wave that traveled backward rather than forwardand refocused on the original point source.

The idea of time reversal is so remote from everyday experience it isdifficult to grasp, but as Scientific American reported at the time, if youstood in front of Fink's time-reversal "mirror" and said"hello," you would hear "olleh," and even more bizarrely,the sound of the "olleh," instead of spreading throughout the roomfrom the loudspeakers, would converge onto your mouth.

In a 1994 experiment, Fink and his colleagues sent sound through a setof 2000 steel rods immersed in a tank of water. The sound scattered along allthe possible paths through the rods, arriving at the transducer array as achaotic wave. These signals were time-reversed and sent back through the forestof rods, refocusing to a point at the source location.

In effect, time reversal is a way to undo scattering.

Combining the tricks

Wang was aware of the work with time reversal, but at first couldn'tsee how it might help solve his problem with tissue scattering.

In 2004, Michael Feld, a physicist interested in biomedical imaging,invited Wang to give a seminar at the Massachusetts Institute of Technology."At dinner we talked about time reversal," Wang says. "Feld wasthinking about time reversal, I was thinking about time reversal, and so wasanother colleague dining with us."

"The trouble was, we couldn't figure out how to use it. You know,if you send light through a piece of tissue, the light will scatter all overthe place, and if you capture it and reverse it, sending it back, it will stillbe scattered all over the place, so it won't concentrate photons."

"And then 13 years after the initial ultrasound-taggingexperiments, I suddenly realized I could combine these two techniques.
"If you added ultrasound, then you could focus light into tissueinstead of through tissue. Ultrasound tagging lets you reverse and send backonly those photons you know are going to converge to a focus in thetissue."

"Ultrasound provides a virtual guide star, and to make opticaltime reversal effective you need a guide star," Wang says.

A time-reversal mirror for light

It's much easier to make a time-reversal mirror for ultrasound than forlight. Because sound travels slowly, it is easy to record the entire timecourse of a sound signal and then broadcast that signal in reverse order.

But a light wave arrives so fast it isn't possible to record a timecourse with sufficient time resolution. No detector will respond fast enough.The solution is to record an interference pattern instead of a time course.

The beam that has gone through the tissue and a reference beam form aninterference pattern, which is recorded as a hologram by a specialphotorefractive crystal.

Then the wavefront is reconstructed by sending a reading beam throughthe crystal from the direction opposite to that of the reference beam. Thereading beam reconstitutes a reversed copy of the original wavefront, one thatcomes to a focus at the ultrasound focus.

Unlike the usual hologram, the TRUE hologram is dynamic and constantlychanging. Thus it is able to compensate for natural motions, such as breathingand the flow of blood, and it adapts instantly when the experimenter moves theultrasonic focus to a new spot.

More photons to work with

Wang expects the TRUE technique for focusing light within tissue willhave many applications, including optical imaging, sensing, manipulation andtherapy. He also mentions its likely impact on the emerging field ofoptogenetics.

In optogenetics, light is used to probe and control living neurons thatare expressing light-activatable molecules or structures. Optogenetics mayallow the neural circuits of living animals to be probed at the high speedsneeded to understand brain information processing.

But until now, optogenetics has suffered from the same limitation thatplagues optical methods for studying biological tissues. Areas of the brainnear the surface can be stimulated with light sources directly mounted on theskull, but to study deeper areas, optical fibers must be inserted into thebrain.
TRUE will allow light to be focused on these deeper areas withoutinvasive procedures, finally achieving the goal of making tissue transparent atoptical frequencies.

Provided by Washington University in St. Louis (news : web)

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