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Lasers in Medicine激光医学

发布时间:2019-07-06 09:01

Over the past half century, lasers have found their way into ophthalmology, oncology, cosmetic surgery, and many areas of medicine and biomedical research.

The possibility of using light in treating illness has been known for thousands of years. The ancient Greeks and Egyptians used sunlight as a therapy and the two ideas were even tied together in mythology, with the Greek god Apollo taking responsibility for both light and healing.

However, it has only been since the invention of the laser 50 years ago, that the potential of light in medicine has really been revealed.

The special properties of lasers make them much better than sunlight or other light sources at targeting medical applications. Each laser operates within a very narrow wavelength range and the light emitted is coherent. They can also be very powerful. The beams can be focused to a very small point, giving them a high power density. These properties have led to lasers being used in many areas of medical diagnosis and treatment.

Lasers repair skin and eyes 

The earliest medical applications for lasers were in ophthalmology and dermatology. Just a year after the invention of the laser in 1960, Leon Goldman demonstrated how a ruby laser, which emits red light, could be used to remove port wine stains, a type of birthmark, and melanomas from the skin.

This application relies on the ability of lasers to operate at a specific wavelength. Lasers are now widely used in dermatology for things like tumor, tattoo, hair, and birthmark removal.

“In dermatology, I probably use a dozen different lasers,” R. Rox Anderson, an SPIE Fellow, dermatologist at the Wellman Center for Photomedicine at Harvard University (USA), and co-chair of the SPIE BiOS symposium, observes in an SPIE video interview. The type of laser and the wavelength of its emissions depend on the type of lesion being treated and what the main absorber is within it. The wavelength also depends on the patient’s skin type.

“You can’t really practice dermatology — or ophthalmology — now without access to lasers. They are mainstay tools of what we do for patients,” he says. The use of lasers for vision correction and a wide variety of ophthalmology applications grew after Charles J. Campbell in 1961 became the first physician to use a ruby laser to treat a human patient with a detached retina.

Later, ophthalmologists used argon lasers (which emit green-wavelength light) to treat detached retinas. This application uses the properties of the eye itself–specifically the lens–to focus the laser beam onto the area where the retina has become detached.

The highly-localized power from the laser causes the retina to reattach.

Patients with certain forms of macular degeneration can be helped with laser surgeries such as laser photocoagulation and photodynamic therapy. In a laser photocoagulation procedure (above), a laser beam is used to seal leaky blood vessels and slow abnormal vessel growth under the macula.
 Illustration © JirehDesign.com

Similar experiments had been tried in the 1940s with sunlight, but doctors required the unique properties of lasers before the work was a success. Another medical approach, also with argon lasers, is used to stop internal bleeding in patients. Green light is selectively absorbed by hemoglobin, the pigment in red blood cells, in order to seal off bleeding blood vessels. This can also be used in cancer treatment to destroy blood vessels entering a tumor and deprive it of nutrients.

“None of these applications could be done with sunlight,” points out SPIE Fellow Abraham Katzir, director of the Applied Physics Group at Tel Aviv University (Israel). “Medicine is very conservative—as it should be—but the laser is gaining acceptance in many medical disciplines. In many applications lasers are replacing traditional tools.”

Both ophthalmology and dermatology have also benefitted recently from excimer lasers, which emit in the ultraviolet range. These lasers have become widely used to reshape corneas (LASIK) so that patients no longer need to wear glasses. They are also used in cosmetic surgery to remove spots and wrinkles from the face.

Profitable cosmetic surgery 

Such technology developments are inevitably popular with commercial investors due to the huge revenue potential. The analyst firm Medtech Insight estimated in 2008 that the market for energy-based aesthetic devices would be worth more than $1 billion by 2011. Indeed, despite a decline in overall demand for medical laser systems during the global recession, laser-based cosmetic surgeries continue to be in regular demand in the United States, the dominant market for medical laser systems, according to a September 2010 Global Industries Analysts report.

“The biggest profit area is really cosmetic, and because of the potential earnings, these areas will continue to be big,” says Leon Esterowitz, biophotonics program director for the National Science Foundation (USA). His main interests for NSF lie in a different area though. “I am most pushing detecting cancer very early. There are some very serious diseases that if you don’t detect them very early, the prognosis is very bad, especially things like pancreatic and ovarian cancer.”

Laser imaging and diagnosis 

Lasers have a major role to play in the early detection of cancer as well as many other diseases. For example, in Tel Aviv, Katzir’s group is looking at infrared spectroscopy using IR lasers. This is interesting, according to Katzir, because cancer and healthy tissue may have different transmissions in the IR range. One promising application of the technique is to measure melanomas. With skin cancers, early detection is very important for the patients’ survival rates. Currently melanoma detection is done by eye, so relies on the skill of the physician.

“In Israel every year, we have a day when everybody can go for free melanoma screenings. Two years ago we took our system to one of the big health centers and were able to see a difference in the IR between the suspect but benign marks and the actual melanomas,” Katzir says.

Katzir, who organized SPIE’s first conference on biomedical optics in 1984, and his Tel Aviv group have also developed optical fibers that are transparent at IR wavelengths so that the technique can be extended to internal investigations. It could provide a quick and painless alternative to cervical smear tests in gynecology, for example.

Laser-based systems are also starting to replace the x-rays traditionally used in mammography. Using x-rays poses a challenge: high intensities are needed to be able to detect cancers well, but as the intensity of the x-ray is raised, so is the risk of the x-ray itself causing cancer. The alternative being studied is to use very fast laser pulses to image breasts as well as other parts of the body such as the brain.

OCT for eyes and beyond 

There is much enthusiasm about the potential of optical coherence tomography (OCT) in many areas of medicine. This imaging technique can give high-resolution (on the order of microns), cross-sectional, and three-dimensional images of biological tissue in real time, using the coherence properties of laser light. OCT is already used in ophthalmology and can, for example, enable ophthalmologists to see a cross section of the cornea to diagnose retinal disease and glaucoma. It is now beginning to be used in other areas of medicine too.


James Fujimoto with a high-resolution, 3D image generated using a laser in combination with the OCT system he co-developed in the early 1990s at MIT.
 Photo courtesy of John Cook, RLE, MIT.

“One of the big areas that’s emerging (for OCT) is fiber optic imaging of arteries,” says SPIE Fellow James Fujimoto of Massachusetts Institute of Technology (USA), a co-inventor of the technology. Fujimoto, also a symposium chair at BiOS, discusses his work with OCT in a SPIE Newsroom video linked to this article online. OCT can be used to assess unstable plaque that is prone to rupture.

Anderson of Harvard agrees about the potential of this technique. “I’m very excited about OCT as an imaging tool for looking at heart vessels. Cardiologists have never been able to see what they are doing. Giving them eyes is a good thing to do,” he says.

In vivo microscopy 

Lasers also play a key role in many different types of microscopy. There have been many medical developments in this area and the aim is to be able to see what is going on inside the body without cutting the patient open.

“Right now the most sophisticated way to remove a cancer is to have the surgeon run back and forth to the microscope to see if he’s got it all,” says Harvard’s Anderson. “The opportunity to do in vivo microscopy and have that happen in real time is very strong.”

One example of an emerging area in medical applications is scanning near-field optical microscopy, which can produce images with a resolution much greater than that obtained from standard optical microscopes. This technique is based on optical fibers that have been etched at their tips at a smaller scale than the wavelength of the laser. This enables sub-wavelength imaging and paves the way for imaging biological cells.

Katzir and colleagues are looking at a version of this technique with IR lasers. “We want to do imaging of individual cells in the IR and maybe see the sub-cell structure,” says Katzir, who sees applications of this in understanding Alzheimer’s disease, cancer, and other changes in cells.

PDT and other treatments 

Developments in optical fibers are helping extend the potential uses of lasers in other ways too. In addition to enabling imaging techniques within the body, these enable the energy of the laser to be transmitted to wherever it’s required. The same optical fiber used in diagnosis could also be used in treatment. Esterowitz of the NSF predicts an increasing use of fiber optics in medical applications. “Fiber lasers are getting much more advanced. In the future this will be a big change in medicine,” he says.

In one type of photodynamic therapy, patients are injected with a light-activated drug called a photosensitizer which is selectively retained by cancer cells. Doctors then use fiber-optic probes to expose the cancer to laser light. This activates the photosensitizer and produces a toxic reaction that destroys the tumor without irreparably damaging the surrounding normal cells.
 Photo courtesy of National Cancer Institute/John Crawford

The area of photomedicine, using light-sensitive chemicals that act with the body in particular ways, also enables lasers to be used in both diagnosis and treatment. In photodynamic therapy (PDT), for example, a laser and a photo-sensitive drug can restore vision for patients with the “wet” form of age-related macular degeneration (AMD), the leading cause of legal blindness in people over the age of 50.

In oncology, some porphyrins will accumulate in cancers and fluoresce if illuminated with a particular wavelength of light to show where the cancer is. If these same compounds are then illuminated with a different wavelength they become toxic and kill the cancer cells.

Personalized medicine 

Another future area of medicine that Esterowitz anticipates for lasers is genetics and epigenetics.

“In the future things will go to the nanoscale and this will enable us to do medicine at a cell level. Lasers, which can operate at femtosecond pulses and be tuned to exact wavelengths, are perfect partners for this,” he says.

This, he predicts, will open the door for personalized medicine, based on what is discovered about patients’ individual genomes, and even changing the genes themselves.

Pioneer of laser medicine: Leon Goldman 

No talk of laser medicine can occur without mentioning Leon Goldman, known as the “father of laser medicine.”

Just a year after the laser was invented, Goldman became the first researcher to use a laser to treat a human skin disease. The technique he used paved the way for later developments in laser dermatology.

His research also led to the application of the ruby laser in retinal surgery in the mid 1960s and to discoveries such as lasers being able to simultaneously cut skin and seal blood vessels to restrict bleeding.

Goldman, who worked for much of his career as a dermatologist at the University of Cincinnati, founded the American Society for Lasers in Medicine and Surgery and helped lay the foundations of current safety assessments of lasers. He died in 1997.

Miniaturization brings changes to laser surgery 

“When I first used a 2-micron laser, it was the size of a king-sized bed and liquid-nitrogen cooled. Now we have diode lasers that can fit into the hand and fiber lasers that are even smaller,” says Leon Esterowitz, biophotonics program director at the National Science Foundation (USA). This kind of change is paving the way for new applications and developments. 

 

“One of the future applications is going to be very small lasers for brain surgery,” he predicts.

 

Technological advances are also driving down costs. Just as lasers have become everyday components in household appliances, they are playing more of a key role in the equipment found in hospitals.

 

“Previously, laser systems were very large and complicated equipment. Now people are starting to make some components out of optical fibers. This decreases the cost, and going to the nanoscale will also reduce costs,” Esterowitz says.

 


Many other laser uses in medicine 

  • Urologists can treat urethral strictures, benign warts, urinary stones, bladder obstructions, and enlarged prostates with lasers.
  • Neurosurgeons use lasers for precision cutting and endoscopic guidance into the brain and spinal cord.
  • Veterinarians make use of lasers for endoscopic procedures, photocoagulation of tumors, excision, and photodynamic therapy.
  • Dentists use lasers for drilling cavities, gum surgery, antibacterial treatments, tooth desensitization, and orofacial diagnostics.

Laser tweezers an aid to biomedical researchers 

Optical tweezers, cell sorters, and a host of other laser-based tools are used by biomedical researchers around the world. Laser tweezers promise better and faster cancer screening and have been used to trap everything from viruses, bacteria, small metal particles, and strands of DNA.


Photo courtesy of UC Davis

Optical tweezers use laser light to hold and rotate microscopic objects, similar to the way we use metal or plastic tweezers to pick up small and delicate objects. Individual molecules can be manipulated by attaching them to a micron-sized glass or polystyrene bead. When a laser beam hits the bead, its light bends and exerts a small force on the bead, pulling it directly into the center of the beam.

This creates an “optical trap” which is able to hold the small particle at its center.


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