Medical lasers in the treatment of cancer| Open Medscience

Table of Contents

Beam Basics: The Science Behind How Lasers Operate
Photoacoustic Imaging
Clinical Applications of Medical Laser Technology
World's Most Powerful Laser
The main features of the laser system are:
- Laser Frontiers: The Convergence of Innovation in Medical, Industrial, and Defense Applications

Medical lasers are used in various clinical applications, including cancer therapy and ophthalmology.

Beam Basics: The Science Behind How Lasers Operate

Max Planck showed that light is released in specific amounts of energy known as quanta and is related to radiation frequency (f). This discovery led to the equation E=hf, where h is Planck’s constant (6.6262 x 10 ^-34Joule⋅second) and is fundamental to medical lasers.

Electromagnetic radiation is emitted from a charged particle (electron) that irradiates energy when it falls from a higher to a lower energy state. Its frequency or wavelength determines the colour of light. The shorter wavelengths are ultraviolet, and the longer wavelengths are infrared.

Quantum mechanics describes the smallest particle of light energy as a photon. The energy (E) of a photon is determined by its frequency (f) and Planck’s constant (h). The difference in energy levels across which an excited electron fall determines the wavelength of the emitted light.

The Planck equation set the foundation of the LASER (Light Amplification Stimulated Emission Radiation), and Albert Einstein 1916 described it as the theory of stimulated emission. This process involved an incoming photon of a specific frequency interacting with an excited atomic electron, causing it to relax back to a lower energy level. These fundamental discoveries of stimulated emission were the basis of the creation of modern lasers. However, it was not until 1960 that Maiman, a physicist at Bell Laboratories, generated a laser from ruby crystal (λ = 694 nm).

However, its practical capabilities began to emerge in the 1940s in the work of Charles Townes and Arthur Schawlow on the development of microwave spectroscopy.

This research led to the invention of the MASER (Microwave Amplification by Stimulated Emission of Radiation). First, however, Theodore Maiman created the first laser using an electrical source to energise a solid ruby.

More lasers were discovered, including the CO2 (carbon dioxide) laser, emitting a concentrated ray of light and absorbing water to vaporise tissue. In addition, the neodymium-yttrium aluminium garnet (Nd-YAG) laser-induced coagulative necrosis within the tissue. Also, visible light lasers were used to produce haemostasis.

Modern medical lasers are used in various clinical applications, including cancer therapy, ophthalmology, nerve stimulation, dermatology, plastic surgery, wound healing and dentistry.

However, the more advanced medical lasers based on the diode are used in cancer therapy. For example, these diode lasers are used in surgical procedures, including soft tissue cutting, coagulation and cancer thermal therapy.

Currently, different types of lasers are capable of undertaking invasive and non-invasive procedures at different depths. The type of laser depends on the region of the electromagnetic spectrum: UV (200-400) µm, visible (400-700) nm, near-IR (700-2900) nm and mid-IR (3-5) µm.

Since the conception of lasers, they have been classified according to the following characteristics:

The laser medium where the amplification occurs can be a solid, liquid, or gas. These types of lasers are referred to as solid-state lasers, liquid lasers, or gas lasers.
Gas lasers, including carbon dioxide, excimer (XeF) and argon, are used in medical lasers.
Dye lasers are examples of liquid lasers, and ruby or yttrium aluminium garnet doped with neodymium lasers are solid-state lasers.
Lasers can emit radiation at different wavelengths in the electromagnetic spectrum’s UV, visible, and IR parts. These are classified as UV lasers, visible lasers, and IR lasers.
Lasers that emit radiation continuously are called continuous-wave (CW) lasers.
Lasers that emit bursts of radiation are called pulsed lasers.

Lasers produce deeper tissue penetration depths in the near-infrared (750-1200) nm than visible lasers. Therefore, procedures that require deep penetrations, such as nano-gold mediated cancer therapy.

The visible lasers (430-680) nm have strong absorption in blood and have been used for oral cancer and retina decreases phototherapy.

Mid-IR lasers (1.9-3.0) µm and (9.3 -10.6) µm have strong absorption in water and tissue. This enables them to remove soft and hard tissue, a procedure known as ablation.

IR lasers (1.3-1.6) µm have been used for minimally invasive procedures such as resurfacing due to their more negligible tissue absorption.

Type of Laser	Wavelength (nm)	Medical Applications
Ruby	694	Dermatology
Nd-YAG	1064	Broad application
Er-YAG	2940	Surgery
Diode	630-980	Surgery, Photodynamic therapy
Argon	350-514	Surgery, Photodynamic therapy, Ophthalmology, Dermatology
Carbon dioxide	10600	Surgery
Pumped-dye	504-690	Photodynamic therapy, Dermatology

Photoacoustic Imaging

Photoacoustic imaging is a hybrid imaging technique based on the photoacoustic effect. It delivers non-ionising laser pulses to tissues and produces heat which initiates thermoelastic expansion to generate an ultrasonic wave. These waves can be detected using ultrasound imaging equipment. This technique can be used to show organs and blood vessels to tumours. Also, more advanced photoacoustic imaging can picture 3-D images of internal body parts and differentiate cancerous cells from healthy cells. This technology platform is called Photoacoustic Topography Through an Ergodic Relay (PATER).

Clinical Applications of Medical Laser Technology

Clinical Application	Medical Procedure
Laser Lithotripsy	Laser lithotripsy is a technique used to break up urinary and biliary stones. The most popular shockwave lasers used in lithotripsy are based on the one-microsecond pulsed-dye laser. They work by the excitation of coumarin dye to produce monochromatic light.
Oncology	Laser interstitial thermal therapy (LITT) is used on patients who are not ideal surgical candidates. LITT is used to treat several cancer types, such as gliomas and meningiomas. Also, mucosal ablation techniques use lasers to treat gastrointestinal cancers, superficial oesophageal cancer, colorectal adenoma and Barrett's oesophagus. Moreover, photodynamic therapy utilises lasers to treat lung cancer lesions.
Cardiovascular Surgery	The trans-myocardial laser revascularisation (TMLR), laser vascular anastomosis and laser angioplasty in peripheral arterial diseases are used to improve blood flow to the heart. TMLR is the only treatment procedure for severe angina and is used in coronary artery bypass grafting. In TMLR, the CO2 laser or the Ho-YAG laser are delivered directly to the target areas of the heart muscle.
Cataract Surgery	The parameters of the ophthalmic laser are set at a specific wavelength, duration, pulse pattern, energy, repetition rate and spot size. These settings produce a monochromatic laser beam that is capable of hitting the same spot within the eye. Therefore, changing the parameters will produce a different absorption in the type of tissue. For example, when using the argon laser, local thermal effects such as photocoagulation can result. Other lasers such as excimer lasers, for instance, Nd-YAG, can be applied in refractive surgery.
Endoscopic Gastrointestinal Surgery	The Nd-YAG laser is used to produce coagulation of gastrointestinal bleeding. It is also used to treat benign small mucosal lesions. Also, the laser is used as a soothing treatment for malignant gastrointestinal disorders in addition to incision treatment for anatomical lesions such as stenosis or cysts.
Oral Surgery	The lasers used in oral surgery include CO2, Er-YAG, Diode and Nd-YAG. They are also used in disinfection and healing.
Dermatology and Reconstructive Surgery	The lasers based on the Nd-YAG and diodes are mainly emitted by infra-red light. These systems target the water in the dermis and heat the collagen in the process to initiate regeneration.

YEAR	INVENTORS/COMPANY	DISCOVERY
1953	Charles Townes, James Gordon, Herbert Zeiger (Columbia University).	The first laser was known as the MASER (microwave amplification by stimulated emission of radiation).
1954	Charles Townes, Herbert Zeiger, James Gordon (Columbia University).	The ammonia MASER obtained the first amplification and generation of electromagnetic waves by stimulated emission.
1955	Nikolai Basov, Alexander Prokhorov (P. N. Lebedev Physical of Institute in Moscow).	They designed and built oscillators and proposed the production of a negative absorption that was called the pumping method.
1956	Nicolaas Bloembergen (Harvard University).	Development of the microwave solid-state MASER.
1957	Gordon Gould.	Coined the acronym LASER.
1958	Charles Townes and Arthur Schawlow (Bell Labs).	The MASERS were able to operate in the optical and infrared regions.
1960	Charles Townes and Arthur Schawlow (Bell Labs).	US patent granted (number 2,929,922) for the optical MASER.
1960	Theodore Maiman (Hughes Research Laboratories).	The first laser was constructed with a cylinder of synthetic ruby.
1960	Peter Sorokin and Mirek Stevenson (IBM Thomas J. Watson Research).	Demonstrated the uranium laser, a four-stage solid-state device.
1960	Ali Javan, William Bennett and Donald Herriott (Bell Labs).	Developed the helium-neon laser.
1961	Trion Instruments, Perkin Elmer and Spectra-Physics.	Lasers began to appear on the commercial market.
1961	Elias Snitzer (American ed Company).	The first operation of a neodymium glass.
1961	Charles Campbell (Institute of Ophthalmology at ed Medical), Charles Koester (American Optical Co. at Columbia-Presbyterian Hospital in Manhattan).	The first medical treatment was used to destroy a retinal tumour using the ruby laser.
1962	Fred McClung	Contributed to the theory of lasers.
1962	Groups at GE and MIT Lincoln Laboratory.	Development of the gallium-arsenide laser.
1962	Nick Holonyak (General Electric).	Gallium arsenide phosphide laser diode.
1963	Logan Hargrove, Richard Fork and M Pollack.	The introduction of the mode-locked laser.
1963	Herbert Kroemer (University of California), Rudolf Kazarinov and Zhores Alferov (A.F. Ioffe Physico-Technical Institute in St. Petersburg, Russia).	The idea of semiconductor lasers was introduced.
1964	William Bridges (Hughes Research Labs).	The invention of the pulsed argon-ion laser.
1964	Townes, Basov, and Prokhorov.	Nobel Prize in physics for quantum electronics and the construction of oscillators and amplifiers based on the maser-laser principle.
1964	Kumar Patel (Bell Labs).	The invention of the carbon dioxide laser.
1964	Joseph Geusic and Richard Smith (Bell Labs).	The neodymium doped YAG laser.
1965	Bell Laboratories.	Two lasers were phase-locked for the first time.
1965	Jerome Kasper and George Pimentel (University of California, Berkeley).	Development of the first chemical laser based on a 3.7 μm hydrogen chloride instrument.
1966	Mary L. Spaeth (Hughes Research Labs).	The invention of the dye laser pumped by a ruby laser.
1966	Charles K. Kao, George Hockham (Standard Telecommunication Laboratories in Harlow, UK).	A breakthrough in fibre optics.
1966	Alfred Kastler	Nobel Prize in physics for the method of stimulating atoms to higher energy states. This technique was known as optical pumping and was influential in developing the MASER and the laser.
1967	Bernard Soffer and Bill McFarland (Korad Corp. in Santa Monica, Calif).	The invention of the dye laser.
1970	Basov, Danilychev (Lebedev Physical Institute).	Development of the excimer laser.
1970	Alferov's group (Ioffe Physico-Technical Institute), Mort Panish, Izuo Hayashi (Bell Labs).	Produced the first continuous-wave room-temperature semiconductor lasers, which led to fibre optic communications.
1970	Arthur Ashkin (Bell Labs).	The invention of optical trapping.
1971	Hayashi, Morton B Panish (Bell Labs).	The first semiconductor laser operated continuously at ambient temperature.
1972	Charles H. Henry	The invention of the quantum well laser.
1972	Bell Labs.	A laser beam to form electronic circuit patterns on ceramic.
1974	Wrigley's	A packet of Wrigley's chewing gum was the first product to be read by a barcode scanner.
1975	NJ Metuchen (Laser Diode Labs Inc).	Engineers develop the first commercial continuous-wave semiconductor laser operating at room temperature.
1975	an der Ziel, Dingle, Miller, Wiegman, Nordland.	The first quantum well laser operation.
1976	Bell Labs.	A semiconductor laser operating continuously at ambient temperature with a wavelength greater than 1 μm.
1976	John M.J. Madey (Stanford University).	The first free-electron laser (FEL).
1977	Bell Labs.	The first commercial installation of a fibre optic lightwave communications system is completed under the streets of Chicago.
1977	Gordon Gould.	A patent was granted for optical pumping.
1978	LaserDisc.	LaserDisc hits the home video market.
1978	Philips.	The launch of the compact disc project.
1979	Gordon Gould.	A patent was granted to cover a broad range of laser applications.
1981	Nobel Prize in Physics.	Schawlow and Bloembergen received the Nobel Prize in physics for their contributions to the development of laser spectroscopy.
1982	Peter F. Moulton (MIT Lincoln Laboratory).	Development of the titanium-sapphire laser.
1982	Audio CD.	The first audio CD was released.
1985	Steven Chu (Bell Labs).	Laser light is used to manipulate atoms.
1987	David Payne (University of Southampton).	Optical amplifiers are used to boost light signals.
1994	Faist, Capasso, Sivco, Sirtori, Hutchinson, Cho (Bell Labs).	The first semiconductor laser was able to emit light, known as the quantum cascade laser, simultaneously.
1994	Nikolai Ledentsov (A.F. Ioffe Physico-Technical Institute).	The first quantum dot laser.
1996	Wolfgang Ketterle (MIT).	The first pulsed atom laser, which used matter instead of light.
1997	Shuji Nakamura, Steven P. DenBaars, James S. Speck (University of California, Santa Barbara).	The development of a gallium-nitride laser was able to emit pulses of bright blue-violet light.
1997	Wind Tunnel Facility (Marshall Space Flight Center).	The application of lasers to measure the velocity and gradient of distortion during a cold-flow propulsion research test.
2003	NASA.	Successfully flies the first laser-powered aircraft.
2004	Ozdal Boyraz, Bahram Jalali (University of California, Los Angeles).	Electronic switching in a Raman laser.
2006	John Bowers (University of California, Santa Barbara), Mario Paniccia (Intel Corp's Photonics Technology Lab in Santa Clara).	The first electrical powered hybrid silicon laser used in the silicon manufacturing process.
2007	John Bowers, Brian Koch (University of California, Santa Barbara).	The first mode-locked silicon evanescent laser.
2009	Chunlei Guo (University of Rochester in NY).	A new process that used femtosecond laser pulses to generate regular incandescent light bulbs.
2009	National Ignition Facility (Lawrence Livermore National Laboratory in Livermore).	Built the largest and highest-energy laser in the world.
2009	NASA.	NASA launched the Lunar Reconnaissance Orbiter.
2009	Intel.	Lasers enter household PCs with Intel's announcement of its Light Peak optical fibre technology.
2009	Nanfang Yu, Federico Capasso (Harvard School of Engineering and Applied Sciences), Hirofumi Kan (Laser Group at Hamamatsu Photonics), Jérôme Faist (ETH Zürich).	Demonstrated the compact, multibeam and multiwavelength lasers emitting in the IR.
2009	Global laser market.	In 2010 the global laser market will grow about 11% and generate total revenue of $5.9 billion.
2010	University of Konstanz. National Nuclear Security Administration. Manijeh Razeghi (Northwestern University). Rainer Blatt, Piet O. Schmidt (University of Innsbruck in Austria). Lawrence Livermore National Laboratory.	Generation of a 4.3-fs single-cycle pulse of light at 1.5-µm wavelength from an erbium-doped fibre laser. NIF was able to deliver 1 MJ of laser energy to a target. Quantum cascade laser efficiency increased to 53%. Demonstrated using a single-atom laser with and without threshold behaviour by tuning the strength of atom-light field coupling. The use of ultrafast laser pulses to probe basic material properties.
2011	Hans Zogg (ETH Zürich). Malte Gather, Seok Hyun Yun (Harvard University). Jianlin Liu (University of California, Riverside).	Developed a vertical external-cavity surface-emitting laser (VECSEL) that operated in the mid-IR at about 5 μm. Demonstrated a laser was able to genetically engineer cells to produce a novel material called green fluorescent protein (GFP) Produced zinc oxide nanowire waveguide lasers.
2012	Yale University. Lawrence Livermore National Laboratory. NASA's Curiosity Rover.	Development of the random laser. 192 UV laser beams produced a peak power above 500 trillion watts. A rock on mars was zapped with a laser.
2013	Stefan Rotter (Vienna University of Technology). Camille Brès, Luc Thévenaz (Ecole Polytechnique Fédérale de Lausanne). Benedikt Mayer (Technical University of Munich).	A laser control layout was developed using granular material to determine the emission direction. Laser pulses travelling down fibre optic cables carry the world's information Demonstrated the use of room temperature laser nanowires that emitted in the near-IR.
2014	Yuri Rezunkov and Alexander Schmidt. European Space Agency. European Space Agency. Lawrence Berkeley National Laboratory. Berkeley Lab Laser Accelerator.	Reported a boost from lasers. This laser ablation has long been proposed for rocket propulsion. Lasers are used to generate a gigabit transmission between a satellite in low Earth orbit and one in geosynchronous orbit (about 45,000 km). A laser from Tenerife connects with a satellite in orbit, providing an optical data path. A new world record for a tabletop particle accelerator (4.25 GeV). A 9 cm long capillary discharge waveguide to generate multi-GeV electron beams.
2015	Brett Hokr (Texas A&M University). Anders Kristensen (Technical University of Denmark). University of St Andrews and Harvard Medical School.	Report on a random Raman laser capable of producing a wide-field, speckle-free image with a strobe time of about a nanosecond. Created a 50 µm wide reproduction of the Mona Lisa. Research involving cells swallowing microresonators.
2016	ASML. Cardiff University, University College London, University of Sheffield.	EUV (extreme ultraviolet) lithography technology resultant in wavelength, much shorter than the 193 nm deep UV lasers used in semiconductor production. Produced quantum dot lasers on silicon.
2017	Jet Propulsion Laboratory. Lockheed Martin. The University of St Andrews, University of Wurzburg, Technical University of Dresden.	Lasers could give space communications broadband. A system produced a single laser beam of 58 kW. Created a fluorescent protein polariton laser.
2018	Lawrence Livermore National Laboratory. National Institute of Standards and Technology. Shanghai Super intense Ultrafast Laser Facility.	The National Ignition Facility laser system set a new record of 2.15 MJ. Showed that a commercial laser could produce 3D images of objects as they melted in a fire. The generation of a 10-petawatt laser burst.
2019	MIT.	Scientists used a 1.9 µm wavelength thulium laser to excite water molecules near a microphone, which transmit an audible signal.

World’s Most Powerful Laser

The Thales and ELI-NP (Extreme Light Infrastructure for Nuclear Physics) projects have developed the world’s most powerful laser. The ultra-high-intensity laser system can produce a pulse at a peak power level of 10 petawatts (1015 W). This laser system is designed to generate twin laser beams of 10 PW and is used in nuclear physics. For example, this type of laser can be used to study key nuclear reactions relevant to nucleosynthesis. In particular, the fusion of α particles and carbon nuclei to produce oxygen (4He + 12C → 16O) is central to life on Earth.

The main features of the laser system are:

The high-power laser system (HPLS) consists of two 10 PW beams that can deliver a laser pulse of up to 225 J in each arm during a laser pulse duration of 15–22.5 fs. The wavelength region is 814 – 825 nm.
The maximum focal spot intensity is I0 ∼ 1023 W cm⁻².
The laser system can deliver lower powers at 100 TW and 1 PW.
The Variable-Energy Gamma Ray (VEGA) system at ELI-NP can deliver monoenergetic gamma rays with up to 19.5 MeV.
The primary performance parameters are a photon density of ∼10⁴ s⁻¹ eV⁻¹, with a high degree of linear polarisation of >95%.
The laser will be able to study the extreme states in gases, solids and plasma.
The laser configuration can be altered to investigate systems that involve non-linear quantum electrodynamics (QED). In addition to vacuum birefringence, relativistically induced transparency (RIT) and nuclear resonance fluorescence (NRF). Including photoactivation, photonuclear reactions and photofission.

Laser Frontiers: The Convergence of Innovation in Medical, Industrial, and Defense Applications

The next generation of lasers will generate powerful beam sources at precisely the right wavelength for all medical and industrial applications. Since the laser conception, they are becoming smaller devices due to the advancement of semiconductors and direct diode lasers. This technology platform led to the Extreme Light Infrastructure for Nuclear Physics (ELI-NP) project, which uses the ultra-high intensity laser system to generate pulses at a peak power level of 10 petawatts. However, laser weapons based on electro-optical systems can increase the lethal power. For example, a high-energy laser system mounted on a US Army Boeing AH-64 Apache attack helicopter. Furthermore, the US Navy has developed solid-state lasers, including the Solid-State Laser Technology Maturation (SSL-TM) effort and High Energy Laser Counter-ASCM Program (HELCAP). However, continued research into LLLT on how to relate the dose to treat a range of clinical conditions in patients in a safe manner.

LASER TYPE	WAVELENGTH (nm)
Argon fluoride	193
Xenon chloride	308 and 459
Xenon fluoride	353 and 459
Helium cadmium	325 - 442
Rhodamine 6G	450 - 650
Copper vapour	511 and 578
Argon	457 - 528
Nd:YAG	532
Helium-neon	543, 594, 612, and 632.8
Krypton	337.5 - 799.3 (647.1 - 676.4 most used)
Ruby	694.3
Laser diodes	630 - 950
Ti-Sapphire	690 - 960
Alexandrite	720 - 780
Nd-YAG	1064
Hydrogen fluoride	2600 - 3000
Erbium: Glass	1540
Carbon monoxide	5000 - 6000
Carbon dioxide	10600