1. Field of the Invention
The present invention relates to diode laser devices that employ laser sources with significant activation thresholds and high temperature sensitivities, which are capable of delivering quasi-continuous or near-continuous wave radiation energy.
2. Information Disclosure Statement
Diode light energy sources that have significant activation thresholds and high temperature sensitivities are rarely employed for applications that require laser energy having wavelengths in the visible red to near IR region because the output power at these wavelengths is limited to an ineffective level. Notably, these sources are seldom employed for applications in photodynamic therapy (PDT), which typically require light energy in the 600-760 nm range, or for environmental sensing and monitoring applications, which require light energy in the 3-3.5 xcexcm range.
PDT is gaining importance both for cancer and non-cancer applications. Typically, this therapy begins with the application of a photosensitizer that may be topically applied, injected, or intravenously introduced to a treatment site. After a suitable time interval depending on certain properties of the photosensitizer, radiation energy in a suitable wavelength band is selectively applied for a predetermined duration and intensity to the target site.
The basic concept of PDT is that certain molecules function as photosensitizers that absorb light of certain wavelengths. If light energy of the proper wavelength is delivered to the photosensitizer, it stores the energy from the photons by increasing its energy to a higher level called a triplet state. Inside the body, some of the excited photosensitizer molecules transfer the stored energy to nearby oxygen molecules, exciting them to a higher energy level called a singlet state. Singlet oxygen is a highly reactive gas that rapidly oxidizes essential cellular components that surround it, and in a living cell this oxidation causes necrosis.
The choice of wavelength depends on the optical absorption characteristics of the photosensitizer, but red light has been favored for its absorption by the photosensitizer, and ability to reach a large tissue volume. A clinically useful photosensitizer should be non-toxic at useful doses, and should concentrate in diseased tissue by either selective uptake or retention. Also, the photosensitizer should be photochemically efficient and ideally be activated by tissue penetrating light ( greater than 600 nm). Most commonly, photosensitizers used in PDT consist of a hematoporphyrin derivative (HpD) such as porfimer sodium, or Photofrin. Although the mechanism of HpD""s preferential location in malignant cells is uncertain, the total time that the derivatives are retained in the malignant tissue is much longer than in nonmalignant tissue, where it generally clears within 24-72 hours. As a result, there is a xe2x80x9cwindowxe2x80x9d of time in which the physician can exploit the differences in HpD concentrations to cause selective photodegradation of malignant tissue.
After photosensitizer administration, a delay of 24-72 hours allows for HpD to be expelled from healthy tissue, and the malignant tissue is irradiated with visible red light tuned to approximately 630 nm. Shortly after administering treatment, the tumor becomes necrotic and, when effectively treated, the tumor becomes a nonpalpable scab that is usually sloughed off within a few days. A high therapeutic ratio and relative lack of morbidity have made PDT a very attractive form of therapy.
While some forms of disease, such as skin disease, are accessible by a wider variety of light delivery systems, others occur inside the body and light energy must be brought to the treatment site using an optical fiber with a suitably configured tip. PDT is most commonly used to alleviate symptoms and diseases associated with cancers of the brain, head, neck, esophagus, skin, colon, and bladder, although PDT treatment can also be applied to other diseases. An example of the latter is age related macular degeneration, one of the most common causes of blindness in patients over 50 years of age. The xe2x80x9cwetxe2x80x9d form of this disease, responsible for 90% of the severe vision loss associated with this condition, is due to choroidal neovascularization, the proliferation of abnormal blood vessels from the choroid, between the retina and the sclera. Fluid leaking from these blood vessels and development of scar tissue are the main reasons for loss of central vision. PDT can be used to slow down the debilitating effects of the disease. The current treatment is relatively unselective, and the heat used to destroy abnormal vessels can induce severe damage to the overlying retina. Application of PDT for this disease involves an intravenous injection of a photosensitizer such as benzoporphyrin derivative monoacid ring A, followed by photoactivation with non-thermal radiation at a wavelength specific for the dye.
PDT is advantageous compared to conventional treatments such as surgery because the procedure can often be carried out in a clinical setting, i.e. in treatment rooms rather than operating rooms. Also, PDT is minimally invasive, safe, cost effective, and highly selective.
High laser powers may not be advantageous in PDT because high power densities can cause tissue ablation, and a main mechanism of PDT is to activate the photosensitizer. However, the laser power must be sufficient (3-4 watts) to effectively penetrate tissue and allow treatment distribution over a large area (several cm). Thus, to maximize necrosis, it is advantageous to employ a laser system for PDT that emits radiation having an activating wavelength of a chosen photosensitizer, and is powerful enough to penetrate to a desired depth without damaging the surrounding areas.
Certain applications, such as the prevention of cell proliferation, that cause restenosis following balloon angioplasty, require delivery of high energy levels through very thin optical fibers (preferably 200 xcexcm diameter). Output powers of 10 to 15 W would be advantageously used, without the risk of thermal damage, because the output radiation is emitted from a long length (several cm) cylindrical tip, that can also be cooled. Short irradiation times are of advantage, as this limits the duration of the treatment.
Continuous wave (cw) sources are preferred in PDT because they can be evenly applied at a treatment site to yield reproducible results and limited treatment times. Moreover, a cw source maintains the greatest amount of photosensitizer in an excited state that leads to elevated levels of oxygen singlets within the diseased tissue.
Due to the inefficiency of semiconductor materials, relatively few diode laser sources are presently available for PDT. The heat generated by a diode laser source often limits the power available at a treatment site to an ineffective level. Diode lasers, however, are very effective at longer operating wavelengths such as 808 nm, and 980 nm, because material science has increased the efficiency of the diodes at these wavelengths. This efficiency is lacking at lower wavelengths, i.e. below about 760 nm, and currently, no diode laser source operating at wavelengths used in PDT is able to effectively emit important photosensitizer activating wavelengths, such as 630 nm, 652 nm, or 732 nm, with sufficient average output power of approximately 3 to 4 watts. In fact, for use in PDT, the Food and Drug Administration (FDA) has only approved a KTP frequency doubled Nd:YAG pumped dye laser and an argon-ion pumped dye laser. These systems are inherently difficult to use. They are bulky, can contain toxic dyes, consume large amounts of electricity, need regular maintenance, and cost well over $100,000.
Diode lasers have distinct advantages over these classical lasers and other solid state lasers including compact size, lower power consumption, and lower maintenance costs. They are much more user friendly, and since a diode laser system typically costs much less than state of the art solid state lasers, laser applications are more available to the public. To take full advantage of the diode laser, there is a need for a diode based laser system capable of transmission of wavelengths within the visible red to near IR region and within the 3.0-3.5 xcexcm range. Thus, the current deficiencies of material science may be overcome and diode lasers could replace solid state lasers in the many applications which require these wavelengths of light energy.
It is therefore an object of the present invention to address the need for a diode laser system that may effectively be employed for use in applications that require light energy having a wavelength in the visible red to near IR range or the 3.0-3.5 xcexcm range.
Another object of the present invention is to provide a diode laser system that multiplexes outputs from diode laser emitters or emitter groups that are injected with drive currents by transistors.
Still another object of the present invention is to provide a diode laser system that can emit radiation having a wavelength below 760 nm with sufficient power necessary for activation of common photosensitizers used in PDT.
It is an aim of the present invention to provide a pulsed laser device utilizing a diode laser source that simulates quasi-continuous wave output to allow for maximum activation of a chosen photosensitizer, leading to necrosis of diseased tissue.
It is a further aim of the present invention to provide a diode laser system that has a narrow and flexible delivery component with a small cross sectional diameter. Maneuverability of the delivery component is thus increased, and it is more easily guided to a treatment site within the mammalian body.
Briefly stated, the present invention provides a multiplexed medical diode laser system that increases power available for applications that require light energy having a wavelength in the visible red to near IR range or 3.0-3.5 xcexcm range. Radiation from a diode laser emitter or emitter group is multiplexed with radiation from other diode laser emitters or emitter groups into a single optics. The diode laser emitters or emitter groups are injected intermittently with current by transistors and thus, a quasi-cw diode laser source may be available. Since the radiation is multiplexed, diode laser emitters or emitter groups can be operated at optimal duty factors and generate less thermal energy, thereby increasing efficiency while maintaining at least near cw output. In a preferred embodiment, large peak and average output powers are obtained with a combination of fast switching transistors that regulate the duty factor of diode laser emitters or emitter groups, and suitable optics that multiplex the outputs.
The above, and other objects, features and advantages of the present invention will become apparent from the following detailed description read in conjunction with the accompanying drawings.