Illuminator for photodynamic therapy

Description of the invention

The present invention relates to an illuminator for photodynamic diagnosis or treatment of a profiled surface. In particular, the present invention relates to a device for photodynamic therapy (PDT) or diagnosis of senile keratosis (PD) on the scalp or parts of a patient's face, as well as other indications (e.g., acne) and other regions of the patient's body (e.g., arms, legs, etc.).

As used herein, the term "visible light" refers to radiant energy in the visible range of the electromagnetic spectrum, and the term "light" refers to radiation energy including ultraviolet (UV), infrared (LR), and visible ranges of the electromagnetic spectrum.

Description of the state of the art

Photodynamic therapy or photochemotherapy is currently proposed for the treatment of several types of skin conditions in or around the skin or other tissues, such as are found in body cavities. For example, PDT has been proposed for the treatment of various types of skin cancer and precancerous conditions. In PDT, the patient is prescribed a light-activated factor or a precursor to a light-activated factor that accumulates in the tissue being diagnosed or treated. The area of ​​the patient's body that contains the tissue to be diagnosed or treated is then illuminated with visible light. Visible light causes chemical and / or biological changes in the light-activated factor which, in turn, selectively locates, destroys, or alters a selected tissue while causing only minor and reversible changes to other tissues in the area.

General references for PDT using LAA as a light-activated factor precursor can be found in U.S. Patent No. 5,079,262, entitled, "Method of Detection and Treatment of Malignant and Non-Malignant Lesions Utilizing 5-Aminolevulinic. Acid "(A method of detecting and treating malignant and benign lesions using levulinic-5-amino acid) by James C. Kennedy et al., Granted January 7, 1992 and in U.S. Patent No. 5,211,938, entitled "Method of Detection of Malignant and Non-Malignant Lesions by Photochemotherapy of Protoporphyrin IX Precursors". ) by James C. Kennedy et al., granted May 18, 1993. The content of these patents is incorporated herein by reference. James C. Kennedy et al. In the Journal of Clinical Laser Medicine and Surgery, November 5, 1996, entitled "Photodynamic Therapy (PDT) and Photodiagnosis (PD) Using Endogenous Photosensitization Induced by 5-Aminolevulinic Acid (ALA): Mechanisms and Clinical Results" ) and photodiagnostics (PD) using endogenous photosensitization, induced by levulinic 5-amino acid (ALA): Mechanisms and Clinical Outcomes) is also included here as source material. "First Phase III", an annual report from DUSA Pharmaceuticals, Inc. (Tarrytown, New York) includes illustrations and application examples of the invention, and is also incorporated herein by reference.

As used herein, the terms ALA or levulinic 5-amino acid refer to ALA itself, its precursors, and its pharmaceutically acceptable salts.

Most traditional non-laser light sources contain only three main functional blocks: an emission source for generating photons (eg a light bulb); coupling means for directing, filtering or otherwise guiding the emitted light to reach its intended destination in a useful form; and a control system for starting and stopping light production at the appropriate moment. The popular, office fluorescent lighting fixture is a good example of such an arrangement. In this hardware, visible white light is produced by a controlled arc in the mercury vapor that excites the inorganic phosphor material inside the glass tube. The energy transfer from the arc emits visible white light from the tube. The emitted visible light is directed towards the workplace by reflectors in the lamp housing; the distribution of visible light towards the destination is often increased by using a scattering system. In a typical office system, the production of visible light is controlled by a simple switch that cuts off the power to the lamp.

PL 192 844 B1

For therapeutic purposes, it is desirable to deliver an emission that is uniform in intensity and color. In particular, it is highly desirable to provide an illuminator with an emitted light spectrum that largely covers the spectrum of optically activating the photosensitizer. According to a preferred embodiment of the present invention, blue light with a wavelength exceeding 400 nm (nanometers) is particularly advantageous for certain diagnostic and therapeutic purposes, particularly when ALA is a light-activated agent used for senile keratosis PD and PDT. However, visible light in other parts of the spectrum, particularly in the green and red ranges between 400 and 700 nm, may also be used.

Traditional illuminators do not produce visible light that is sufficiently uniform in intensity on the profiled surface.

The essence of the invention

It is an object of the present invention to provide an improved illuminator for PDT and / or PD.

Another object of the invention is to provide a PDT illuminator that produces visible light with a high degree of uniformity in terms of both spectral characteristics and intensity on the profiled surface in a differentiated manner. The term profiled surface as used herein refers to a non-planar surface.

Yet another object of the invention is to provide an illuminator for a PDT or PD that produces visible light almost entirely in a selected wavelength range.

Another object of the present invention is to provide an illuminator for illuminating a patient's face or head.

Yet another object of the present invention is to provide an illuminator with a cooling system improving the uniformity of the radiation intensity of the illuminator.

An additional object of the present invention is to provide an illuminator comprising a finite emitter which approximates the uniform emission of the emitter with an infinite plane by varying the distance between the individual light sources within the illuminator.

Yet another object of the present invention is to provide an illuminator with a system that monitors the visible light emitted from the plurality of light sources and emits a signal to regulate the emission of visible light from the plurality of light sources.

According to the invention, an illuminator for photodynamic diagnosis or treatment of a profiled surface, comprising a housing in which a plurality of light sources are mounted illuminating the surface with substantially uniform intensity, is characterized in that the light sources are bent such that they are generally parallel to the profiled surface. and illuminate the surface with visible light, and the housing keeps bent light sources at a proper distance from the profiled surface.

Each of the curved light sources may include a generally arcuate center region and arms extending from the respective ends of the center region, and the housing includes an aperture allowing a profiled surface to be inserted between the arms toward the center region. The central region is generally semicircular and the arms extend generally parallel to one another from the respective ends of the central region. The arcuate center region has a radius of curvature of approximately 19 centimeters.

The casing arms are connected to a cooling system adapted to provide increased cooling to the central region and its ends than to the central region.

The housing supports a reflector disposed between the housing and the plurality of light sources, and a shroud is secured to the housing between the plurality of curved light sources and the profiled surface, and the cooling system includes inlet openings in the shroud adapted to allow ambient air to pass therethrough; and in the reflector there are intermediate openings adapted to transmit heated air from the first zone between the reflector and the shield to a second zone between the reflector and the housing, and outlet openings in the housing adapted to remove the heated air.

The housing houses at least one fan adapted to direct ambient air through the inlet openings and remove the heated air through the outlet openings. The inlet openings include perforations in the shell near the free ends of the arms, and the intermediate openings include perforations in the reflector near the ends of the center region.

PL 192 844 B1

Multiple bent light sources are generally parallel to each other, and the lateral distance between adjacent bent light sources varies along the profiled surface. The lateral distances between internal light sources are greater than that between external light sources.

The housing surrounds the emission region and the plurality of bent light sources are seven fluorescent lamps having a first distance transversely from the innermost fluorescent lamp to each adjacent fluorescent lamp, a second distance transversely between the intermediate fluorescent lamps on each side of the innermost fluorescent lamp a third distance in the lateral direction between the outermost fluorescent lamps and corresponding adjacent, intermediate fluorescent lamps, and a fourth distance in the lateral direction between the outermost fluorescent lamps and the edges of the emission region and the first distance in the lateral direction is approximately 7 centimeters, the second distance in the lateral direction it is approximately 5 centimeters, the third transverse distance is approximately 3.5 centimeters and the fourth transverse distance is approximately 2.5 centimeters.

Bent light sources generate visible light essentially entirely in the blue range of the spectrum. The light has a nominal wavelength of 417 5 nanometers and a nominal bandwidth of 30 nanometers.

Many bent light sources contain a fluorescent tube lined on the inside with Sr2P2O7: Eu.

The numerous curved light sources have a maximum total emission region of approximately 2,850 square centimeters and a minimum therapeutically active emission region of approximately 1,350 square centimeters.

A shield can be positioned between the multiple curved light sources and the contoured surface, supported by the housing, and multiple light sources in the active emission region approximately 5 centimeters (2 inches) from the shield and about 10 centimeters (4 inches) from the shield have the radiant intensity. equal to at least 70% of the maximum radiation intensity. The radiation intensity of multiple bent light sources in the active emission region, at all working distances from the shield, is at least 60% of the maximum radiation intensity.

The radiation intensity of multiple bent light sources is approximately 9 to 11 milliwatts per square centimeter. The radiation intensity is approximately 10 milliwatts per square centimeter.

In another embodiment of the invention, an enclosure supported by the housing is positioned between the plurality of light sources and the contoured surface, the shield filtering out ultraviolet radiation emitted by the plurality of bent light sources towards the contoured surface. The cover is made of polycarbonate. The cover includes a light diffuser.

In a further embodiment of the invention, the plurality of bent light sources comprises at least one power electronic circuit which includes an activation / deactivation controller for supplying / interrupting power to the plurality of bent light sources; an exposure controller for interrupting power to the plurality of bent light sources, when a selected dose of light irradiates the profiled surfaces, and a starter to initiate and maintain voltage across the plurality of bent light sources. The exposure controller is a timer for interrupting the supply of multiple light sources after a predetermined time. The clock comprises at least one regulating element for determining the time of exposure of the profiled surface to said light. At least one electronic circuit includes a visible light sensor for measuring the intensity of light from at least one of the plurality of light sources and for producing a first signal, representative of the light to be measured; a detector for monitoring the input voltage of a starter and for producing a second signal, representative of the input voltage being monitored; a transformer to supply a plurality of input voltages to the starter; a set of switches for selecting one of a plurality of input voltages to provide to a starter and a processor for controlling operation of said at least one electronic circuit and for receiving first and second signals and controlling the set of switches; the processor adjusts the input voltage of the starter to adjust the light intensity from the plurality of bent light sources such that the intensity of the visible light illuminating the profiled surface is maintained substantially uniform. The transformer is a step-down-step autotransformer. At least

One electronic circuit includes an indicator for indicating the status of the illuminator, controlled by a processor. The activation / deactivation controller includes a main power switch to control the power supply from an external source and a key switch to prevent the use of the illuminator by unauthorized persons.

The housing supports a visible light sensor and a reflector disposed between the visible light sensor and the plurality of curved light sources; the reflector has a first aperture adapted to transmit visible light from the first of the plurality of bent light sources to the visible light sensor, the first aperture being spaced from the visible light sensor by a first distance and having a first cross-sectional area, and the reflector is a second aperture adapted to transmit visible light from the second of the plurality of bent light sources to the visible light sensor, and the second opening is spaced a second distance from the visible light sensor and has a second cross-sectional area; wherein the ratio of the first and second cross-sectional areas is proportional to the inverse of the squares of said first and second distances, and the visible light sensor is adapted to monitor the intensity of the light emitted from the first and second light sources and produce a signal to adjust the intensity of the visible light emitted by the plurality of sources lights, so that an essentially uniform intensity of visible light illuminating the profiled surface is ensured.

There is a third aperture in the reflector adapted to transmit visible light from a third of the plurality of bent light sources to a visible light sensor, the third aperture spaced a third distance from the visible light sensor and having a third cross-sectional area; and of the plurality of curved light sources, the second and third are substantially equidistant from opposite sides of the first of the plurality of curved light sources, the second and third distances are substantially equal and said second and third cross-sectional areas are substantially equal; and the visible light sensor is adapted to monitor the intensity of the light emitted by the first, second and third of the plurality of bent light sources and generate a signal, to adjust the intensity of the visible light from the plurality of bent light sources, such that a substantially uniform intensity of the visible light illuminating the profiled surface is provided .

The illuminator described above is used to illuminate a profiled surface with topically applied LA-5-amino acid. LA-5-amino acid is provided in the vehicle. LA-5-amino acid is supplied in consecutive portions. The emitted light is basically in the blue range of the spectrum. Irradiation comprises approximately 1000 seconds of exposure to light having a nominal wavelength of 417 5 nanometers and a nominal bandwidth of 30 nanometers.

The plurality of bent light sources and their circuits form an emission region for emulating an emitter with an infinite VH emission plane, generally parallel to one another and adapted to emit light of substantially uniform intensity from said emission region; the first distance in the lateral direction between adjacent light sources varies with respect to the circumference.

The first distance in the transverse direction is greater between adjacent light sources distant from the perimeter than between adjacent light sources that are close to said perimeter. The plurality of light sources comprises a first pair of bent light sources disposed parallel to each other and spaced from the periphery by a first distance; a second pair of bent light sources positioned parallel to the first pair and spaced apart from the respective source of the first pair by a second distance in the lateral direction; a third pair of curved light sources parallel to the first and second pairs and spaced from the corresponding source of the second pair by a third lateral distance, and at least one center curved light source parallel to the first, second and third pairs and spaced from adjacent curves light sources a fourth distance in the lateral direction; the first, second, third and fourth distances being in the approximate ratios of 2.5: 3.5: 5: 7, respectively.

According to the present invention, a profiled surface PDT or PD illuminator comprises a plurality of light sources generally aligned with the profiled surface and illuminating the profiled surface with visible light of substantially uniform intensity and a housing supporting the plurality of light sources generally parallel to the profiled surface.

PL 192 844 B1

The PDT or PD method of a profiled surface typically comprises supplying LAA on the profiled surface and illuminating the profiled surface with visible light of substantially uniform intensity from multiple light sources placed generally parallel to the profiled surface.

The illuminator cooling system comprises an elongated light source having a generally arcuate segment connected to the generally straight segment. Generally the straight segment and the connection between the generally arcuate and straight segments receive more cooling than the generally arcuate segment.

According to the present invention, an illuminator for emulating an infinite plane emitter comprises an emitting surface having a circumference and a plurality of light sources that are generally parallel to each other, said plurality of light sources being adapted to emit light of substantially uniform intensity from said emitting surface. The lateral distance between adjacent light sources varies along said circumference.

In order to achieve the above-mentioned purposes, a monitoring system for an illuminator illuminating a surface is also provided. The monitoring system comprises a plurality of adjustable light sources adapted to illuminate a surface with light of a substantially uniform intensity; a light sensor supported in correspondence with the plurality of light sources; a partition between the light sensor and the plurality of light sources; a first opening in the partition adapted to transmit light from the first of the plurality of light sources to the light sensor, the first opening spaced from the light sensor by a first distance and having a first cross-sectional area and a second opening in the partition adapted to transmit light from the second from numerous light sources to the light sensor, the second opening is spaced a second distance from the light sensor and has a second cross-sectional area. The ratio of the first and second areas is proportional to the reciprocal of the squares of the first and second distances; the light sensor is adapted to monitor light emitted from the first and second sources of the plurality of light sources and outputs a signal to regulate the light emission from the plurality of light sources so as to provide light of substantially uniform intensity illuminating the surface.

In order to achieve the above-mentioned objectives, a light is also provided according to the present invention for the photodynamic diagnosis or treatment of a profiled surface, the light being emitted by a plurality of sources, provided generally parallel to the profiled surface and illuminating the profiled surface with uniform intensity.

The present invention is based on similar principles to the fluorescent illumination system described above. According to an embodiment of the present invention, visible light is produced by fluorescent tubes equidistant from the profile surface and the associated control electronics; the visible light emitted by these pipes is directed towards the surface to be diagnosed or treated by shapes generally parallel to the profiled surface of the pipes and their elements, such as a reflector; the activation of the fluorescent tubes and the visible light illumination of the profiled surface are regulated by electronic circuits.

The present invention differs from traditional light sources because of the biological requirements placed on the light source used for PDT. A much greater degree of accuracy and integration is required with respect to the components of the present invention. The output spectrum, exposure time and uniformity of illumination must be controlled to ensure that the characteristics of the device are suitable for delivering light to lesions and eliciting a photodynamic response. In order to achieve this, each functional block within the present invention comprises carefully selected and processed elements. The principles of operation of each functional block are described in detail below.

The inverse-square law for optics says that the intensity of light from a point source, perceived by an object, is inversely proportional to the square of the distance from the source. For this reason, the distance to the source is an important variable in all optical systems. Thus, in order to obtain homogeneous illumination of the face or head, variations in the illumination output as a function of distance must be minimized. A flat emitting surface will not deliver a dose of uniform light to all parts of the face at the same time because the non-planar surfaces of the face and head cannot be placed at a constant distance from the emitting surface. In order to solve this problem, the present invention employs a U-shaped emitting surface that better reproduces the profiles of the human face and head and minimizes the difference in the distance between the lamp and the object which, in turn, minimizes the differences in the illumination of the object.

PL 192 844 B1

Since the emission of cylindrical light sources can vary with temperature, the temperature distribution also plays an important role in achieving homogeneous illumination. Then, since the emission from the tube can vary with its length, the selection of the temperature distribution can be used to adjust the uniformity of the radiation of the illuminator.

The illuminator according to the invention provides a uniform distribution of the intensity of visible light.

Additional objects, features and advantages of the invention will be set forth in the following description, and in part will be apparent from the description, or may be learned from practice of the invention. The objects and advantages of the invention can be realized and achieved with the devices and combinations detailed in the appended claims.

The subject matter of the invention is illustrated in the exemplary embodiments in the drawing, in which fig. 1 shows a partially cross-sectional front view of an illuminator according to the present invention, fig. 2 - a partially cross-sectional side view of the illuminator shown in fig. a partially cross-sectional plan view of the illuminator shown in Fig. 1, Fig. 4 - details of a light source in the form of a fluorescent tube, shown in Fig. 1, Fig. 5 - details of the headlamp shown in fig. 1, fig. 6 - details of the cover shown in fig. 1, fig. 7 - electrical wiring diagram in the illuminator shown in fig. 1, fig. 8 - starter circuit diagram in the illuminator shown in fig. Fig. 1, Fig. 9 shows a modified wiring diagram in an illuminator according to the present invention, Figs. 9A-9D - details of the electrical circuit diagram shown in Fig. 9, Fig. 10 - spectrum of the typical fluorescent emission from a light source in the form of a fluorescent tube shown in Fig. 4, Fig. 11 - a monitoring system according to the present invention.

Detailed description of the preferred embodiments

According to the preferred embodiment shown in Figs. 1-8, seven U-shaped fluorescent tubes 10 (1) - 10 (7) are powered by three electronic starters 20. Regulating the voltage of the starter changes the intensity of the radiation emitted by the tubes. The tubes 10 (1) - 10 (7) are supported by the housing 30 and are covered by a polycarbonate cover 40 which directs the cooling air flow inside the device and prevents contact between the glass and the patient in the event of a tube breakage. An aluminum reflector 50, positioned downstream of the tubes, increases both the output radiation and the homogeneity of the output radiation distribution. The overall dimensions of the device are approximately 38 cm (height) x 45 cm (width) x 44.5 cm (diameter). Fig. 1 shows the position of the patient's head and nose.

Examples of light sources

According to a preferred embodiment of the present invention, seven F34T8 Ultra Blue fluorescent tubes with a length of 36 inches provide a visible light emission surface of maximum 36 cm high and 46 cm wide (approximately 2S50 cm).²), with a minimum therapeutically active area of ​​30 cm high and 46 cm wide (approximately 1350 cm²). As shown in Figure 1, the tubes have a generally arcuate center region 10A and arms 10B extending from respective ends of the center region.

Fluorescent tubes are a type of gas discharge lamp. They use an electrical discharge in a low pressure gas to produce a plasma that interacts with a fluorescent phosphor to convert electricity into light. A typical fluorescent tube consists of a sealed glass tube with electrodes or cathodes at both ends. The inside of the tube is covered with a homogeneously luminous, inorganic crystalline phosphor. The tube is filled with a low pressure inert gas, usually argon, to which a small amount of liquid mercury is added before the tube is closed. The low pressure inside the tube causes some of the liquid mercury to evaporate, creating an atmosphere of argon and mercury vapor inside the tube. Applying a sufficiently high voltage between the cathodes causes the emission of electrons from the cathode, which as they move along the tube ionize the mixture of argon and mercury vapor. Upon ionization, the gas mixture inside the tube becomes conductive, allowing electric current to flow and further excite the mercury atoms. The intensity of the current flowing through the pipe regulates the number of atoms excited and therefore also the intensity of the light emission from the pipe. When the excited mercury atoms return to a lower energy state, they emit ultraviolet (UV) light. UV radiation is absorbed by the phosphor on the wall of the tube, causing the phosphor to fluoresce, effectively converting the mainline energy

Resonant mercury at a longer wavelength. The chemical composition of the phosphor material determines the spectrum characteristics of the light emitted from the lamp. This can be used to select the wavelength of the emitted light as required by the application, as in the case of the present invention.

The emission of radiation from the fluorescent tube is not uniform. The intensity measured in the immediate vicinity of the cathode is usually low compared to the intensity of the emission from the rest of the tube. This is because the ionized gas near the cathode does not emit as much UV light as to excite the phosphor. The region of reduced emissions is known as the Faraday darkroom. In order to avoid non-uniformity problems, a plurality of U-shaped tubes 10 (1) - 10 (7) are used in one embodiment of the present invention. This arrangement allows the cathodes and their associated low-emissivity regions to fall outside the box. an active emissive surface (basically behind the patient's ears). Only the more uniform center portion of the tube radiation is used to treat the patient. Another advantage of the system is that the non-uniformity can also be controlled by varying the distance between the pipes in the transverse direction (in the horizontal direction according to Fig. 2). This is important because it has to be compensated for the fact that the radiation intensity from the flat plane light source decreases near the edge. By varying the distances between the tubes in the transverse direction produces the same effect as bending the edges of a larger illuminator, thus emulating an infinite area emitter in a compact device.

The U-shape adopted for the tubes minimizes the differences in the distance between the emitter and the object, providing a uniform distribution of visible light on the patient's face or head; The dimensions of the tube were selected based on the average dimensions of an adult patient's head. Pipe installation minimizes the impact of non-emitting regions at their ends. This allows the present invention to be made more compact and to better position the patient's head among the visible light sources. Moreover, the "U" shape provides the desired radiation intensity and radiation uniformity for head and face illumination and thus ensures that the correct dose of visible light is delivered to all regions of the object during PDT.

The number of tubes used and the distance between them were selected in order to achieve the desired parameters of uniformity and intensity of the emitted radiation. The optimal intensity distribution has been found to occur when seven pipes 10 (1) - 10 (7) are placed symmetrically in the housing with respect to opposite edges of the device with the following approximate distances in the transverse direction: 7 cm between the center pipe 10 (4) and each of them. two pipes 10 (3), 10 (5) adjacent to the central pipe 10 (4); 5 cm between pipes 10 (3), 10 (2) and 10 (5), 10 (6), i.e. in the next pairs of pipes from the center, and 3.5 cm between pipes 10 (2), 10 (1) and 10 (6) ), 10 (7), i.e. in the outermost tubes on the sides of the unit. The outermost tubes 10 (1), 10 (7) are about 2.5 cm from the edge of the housing. The present invention provides very homogeneous illumination without the use of an additional diffuser. However, it is also envisioned that the diffuser can also be provided to the cover 40.

Fluorescent tubes according to preferred embodiments of the present invention use the commercially available Sr2P2O7: Eu phosphor which is used in the diazotypy process. When such a phosphor absorbs the UV radiation emitted by mercury, it emits in the blue spectral range with a wavelength of 417 nm (nominal) and a spectral width of 30 nm. A typical fluorescence emission spectrum of the pipes of the present invention is shown in Fig. 10. According to a preferred embodiment of the present invention, the spectrum of the radiation emitted is selected according to the absorption spectrum of protoporphyrin IX, a photosensitive substance that is produced from ALA in the tissue of the object. Radiation in a different spectral range may be delivered using a different phosphor inside the tubes. A different range of the emission spectrum may also be provided using other light source manufacturing technologies.

Electrical parameters

To obtain satisfactory performance from the fluorescent tube, it is necessary to apply a voltage to the cathodes of the tube to initiate the conductivity of the tube and then regulate the current through the tube. Fluorescent tubes using gas discharge are particularly sensitive to the voltage and current used to drive them. Higher current intensity increases the number of generated electrons, resulting in an increase in the intensity of the emitted light. But the greater current causes the cathode temperature to increase, potentially increasing cathode material erosion and contamination

The atmosphere of the tube through the material removed from the cathode; this leads to a reduction in the service life of the pipe. Too little current flowing through the pipe may cause the pipe wall to be too cold, which will result in the condensation of mercury vapor, negatively affecting the uniformity of the intensity of the emitted radiation. Then, for most tube designs, it is necessary to heat the cathodes to obtain proper initiation of the tube discharge. The regulation of the voltage and / or current characteristics in the tube and the heating of the cathodes are accomplished by external electronic circuits which are usually assembled and placed in a single device, called a "starter". Different designs of the starter are possible; from simple electromagnetic coils to sophisticated electronic circuits that optimize and control various aspects of tube performance.

According to a preferred embodiment of the present invention, each starter 20 comprises three main functional blocks: an input filter circuit, an oscillator circuit, and a high frequency transformer.

The input filter circuit rectifies the AC voltage from the 120 VAC line, creating an internal DC voltage that can be used by the oscillator. The filter also prevents noise on the AC line from adversely affecting the operation of the starter and prevents the oscillator transients from going backwards to the AC line. Finally, this circuit provides power factor correction so that the peak current drawn by the starter from the AC line is less than that of a simple rectifier. It is also possible to supply the preferred embodiments of the present invention with constant voltage.

The oscillator provides a mechanism for transmitting electrical energy in each starter device 20; it includes a pair of keying transistors connected to a resonant circuit that includes an output transformer. A small signal from the output transformer is fed back to the inputs of the keying transistors, causing them to oscillate when a DC voltage is applied. The oscillation energy is coupled to the tubes through the transformer. With this design of the starter, the amount of oscillation is proportional to the DC voltage which, in turn, is proportional to the voltage on the AC line. Since the transformer is also connected to the cathodes of the pipes, the amount of current flowing through the pipes is proportional to the alternating voltage on the AC line. This is known as a non-constant wattage design and was chosen in order to be able to adjust the intensity of the output lighting according to the present invention.

The high-frequency transformer transfers energy to the tube and performs several other important functions. Provides electronic transformation of voltage and current limiting impedance levels to deliver the correct voltage and current to pipes for proper and safe operation. It also provides feedback to the oscillator, which helps to stabilize its operation and provides a mechanism for generating an initial high-voltage start-up pulse.

The additional transformer windings provide the current for heating the tube cathodes. This lowers the voltage level needed to initiate the discharge and reduces cathode damage from the initial current pulse.

Due to changes in the tube manufacturing process, the intensity of the light emitted must be adjusted to meet the requirements for the specific PDT purposes. Thereafter, the intensity of the emitted illumination must be adjusted as the tubes age to compensate for the degradation of the tubes themselves. In a preferred embodiment of the present invention, the starters 20 are non-constant wattage starters whereby the tube emission can be controlled by varying the input voltage applied to the starter. According to a preferred embodiment of the present invention, 40% variations are possible by using two step down / step up autotransformers 60w AC line.

The voltage of the starter can be adjusted manually or automatically. According to embodiments of the present invention where manual voltage regulation is used, the appropriate starter voltage is determined by the technician manually by selecting the terminals on the two step-down / step-up autotransformers 60. Since AC line voltage variations affect the voltage of the starter, external voltage stabilization can be used to improve the stability of the emitted radiation. Another preferred embodiment of the present invention has automatic voltage regulation, including an "active" circuit, comprising electronic switches activated by a microcontroller to eliminate the need for external voltage stabilization and the need for the technician to regulate the voltage of the starter as the emitted tube radiation decreases in intensity over time. The microcontroller receives input signals from optical sensors

And voltage, and then activates a suitable electronic switch in order to keep the intensity of the emitted radiation within a certain range. The active keyer can also correct for changes in emission intensity due to line voltage and temperature changes during operation; thus, stabilization of the external line voltage is not needed in the preferred embodiment of the present invention using the active-keying circuit. Automatic voltage regulation according to a preferred embodiment of the present invention is described in more detail below.

According to a preferred embodiment of the present invention, three electronic starters 20 with fast starting are used to power seven fluorescent tubes 10 (1) - 10 (7). Two starters 20 (1) and 20 (3) power two tubes 10 (1), 10 (7) and 10 (2), 10 (6) respectively, and one starter 20 (2) powers three tubes 10 (3) - 10 (5). These starters convert the voltage from the 120 VAC line, available in a standard mains socket, into a high-frequency sinusoidal current (approx. 25 kHz), suitable for feeding fluorescent tubes. High frequency operation is desirable to reduce the optical emission ripple that occurs in all fluorescent tubes and to increase the overall intensity. The ripple of the emitted radiation is the small variation in the tube's emission intensity relative to the sinusoidal alternating tube current used to support the arc in the plasma.

Visible light transmission parameters

In order to use the visible light emitted from the back of the tube and to increase the homogeneity of the intensity distribution, a reflector 50 is provided approximately 10 mm from the rear surface of the tubes. The reflector 50 is made of a polished aluminum sheet that is bent to suit the configuration of the tubes.

The emitting surface of the present invention is covered with a plastic sheath 40, and has low UV transmission. In a preferred embodiment of the present invention, the plastic cover 40 is made of polycarbonate. With the fluorescent tube production technology used, a small UV emission remains in the emitted radiation. Polycarbonate has a very low transmission in the ultraviolet range of the spectrum and effectively filters out any residual UV emission from the visible light emitted by the device. The cover 40 also protects the patient from injury in the event of a tube breakage.

Cooling parameters

Since the temperature of the cathode and tube wall strongly influences the emission intensity distribution, a cooling system is provided to ensure proper operation of the lamp. According to an embodiment of the present invention, the cooling system includes openings in the polycarbonate shell 40, reflector 50 and housing 30, and fans 70 for moving cooling air.

Ambient air is supplied to the interior of the present invention through inlet openings 42 in the polycarbonate sheath 40. The space between the sheath 40 and the reflector 50 forms a first zone (i.e., chamber) in which ambient air passes over the pipes 10 (1) - 10 (7). The air is heated by the pipes and is directed from the first zone to the second zone between the reflector 50 and the housing 30 through openings in the reflector 52. Reflector openings 52 are provided at an angle of ± 45 ° in order to provide a proper temperature distribution in the wall of the tubes. The heated air is exhausted by four fans 70 through exhaust openings 32 in housing 30.

In accordance with a preferred embodiment of the present invention, a plurality of inlet openings 42 (thirty-six shown) in the polycarbonate sheath 40 are equally spaced along each edge immediately above the cathode regions of the tubes. Holes 52 in reflector 50 are pairs of slots made in the columns from top to bottom; the reflector openings 52 directly face the fans 70 which are provided at an angle of ± 45 from the center of the device.

The straight tube segment between the cathode region a bent tube segment "U" produces a slightly higher emission intensity than the central portion of the bent segment. This can be attributed to the difference in the thickness of the phosphor coating caused by the bending process. To further increase the homogeneity of the emission intensity, the reflector openings 52 are provided in the reflector 50 such that cooling air flows mainly through the straight section and the end portions of the bent section. Less cooling air flows over the center of the tubes between sets of reflector holes 52, causing

The temperature of the pipe wall is higher in this region. As the emission of radiation in such a tube increases (to some extent) with increasing wall temperature, the warmer center region of the pipe produces a greater radiation intensity than the rest of the pipe and compensates for the lower emission efficiency of the center region.

Basic regulatory functions

User-operable adjustments in accordance with the preferred embodiment of the present invention include a main power switch 80 located on the rear of the housing 30 and a key switch 90 and a timer 100 located on the side of the housing 30. The timer 100 includes an exposure time indicator 102 that displays the remaining exposure time.

The main power switch 80 is part of a fused power input module that includes a two-position tilt switch and a standard interconnect cord that complies with the International Electromechanical Commission (IEC) standard. By pushing the tilt switch to the "1" position, energy is supplied to the device. The fans 70 are working but the tubes 10 (1) - 10 (7) do not light until the ignition switch 90 is turned on and set and timer 100 is activated. When the main power switch 80 is in the "0" position, all electrical components within the present invention are disconnected from the AC line. The power input module provides overcurrent protection for the present invention and current limitation in the event of a voltage impulse on the power line; the main power switch 80 will not supply power to the device if any fuse in that module is blown.

The key switch 90 provides a means by which the use of the present invention can be restricted to authorized personnel. According to a preferred embodiment of the present invention, operation of the timer 100 and tubes 10 (1) -10 (7) requires insertion of the key and anti-clockwise ¼ turn to the "ON" position. This activates timer 100 so that a prescribed exposure time can be entered.

According to an embodiment of the present invention, the system clock 100 directly controls the operation of the fluorescent tubes 10 (1) - 10 (7). It includes three adjustment / control buttons 104: one start / stop button and two time setting buttons, as well as the exposure time indicator 102. The timer 100 is used to set a desired exposure time and to initiate visible light exposure. Automatically turns off the pipes of the present invention after a predetermined exposure time.

The two time setting keys 104 are preferably membrane switches that allow the user to set the exposure time. Pressing the up arrow key 104 increases the time, and depressing the down arrow key 104 reduces the time. After the first keystroke, the data on the display changes slowly. If the keys are held down for a long time, the displayed numbers change faster. Small adjustments to the displayed time can be made by quickly pressing and releasing the keys. In this way, the user can set a fixed exposure time.

The start / stop key 104 is a membrane switch that controls the operation of the tube; toggles between on and stopped states for pipes and clock. After the exposure time is set, pressing the key 104 activates the tubes and initiates a timer downcount. Pressing a second time turns off the tubing and stops the timer, providing a means to interrupt the treatment if necessary. If the start / stop key 104 is not pressed a second time, the timer will automatically turn off the tubes when the downcount is complete. Illumination may also be interrupted, if desired, by turning the key to the "OFF" position or by pushing the main power switch lever 80 to the "0" position.

The exposure time indicator 102 in clock 100 is preferably a four-digit LED display that gives the time in minutes and seconds. Before pressing the start / stop key 104 to initiate exposure, the display 102 indicates the exposure time set. When the start / stop key 104 is pressed to initiate the exposure, the exposure time indicator 102 counts down and displays the exposure time remaining. Pipes will automatically shut off when display shows "00:00".

Power is supplied by a three-wire hospital-grade electrical cord. The power requirements according to an embodiment of the present invention are as follows: 120 VAC,

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2.5 A, 60 Hz, the voltage from the AC power line is stabilized by an external, commercial voltage stabilizer (eg SOLA MCR1000 - constant voltage transformer).

Automatic control functions

According to a preferred embodiment of the present invention, the need for the technician to adjust the starter voltage as the tube emission intensity decreases over time is eliminated by providing automatic regulation of the starter voltage. This can be accomplished by replacing the manual selection of jumpers at the terminals with an "active" circuit of electronic switches activated by a microcontroller (Figures 9 and 9A-9D). The microcontroller receives input signals from optical and voltage sensors, and then activates the appropriate electronic switch to maintain the emission intensity within a specified size range. The active keyer can correct for variations in emission intensity due to variations in the supply line voltage and temperature variations during illumination; thus, external stabilization of the mains voltage is not required according to the preferred embodiments of the present invention using automatic regulation of the voltage of the starter. All other elements of the automatic voltage adjustment of the starter according to the embodiments of the present invention, including the tubes 10 (1) -10 (7), the starters 20, the reflector 50, and the polycarbonate sheath 40 are the same as the manual adjustment embodiments.

According to a preferred embodiment of the present invention, the electronic control system 110 comprises six functional blocks. The microcontroller 200 is the central processing unit; it includes modules that read data from the sensors of the device, determines the state of the device, regulates the voltage of the starter (and the intensity of the tube emissions), and provides the user with information via the LED display 112 (the modules are described in greater detail below). In order to achieve a predetermined level of emission intensity, the microcontroller 200 monitors the emission intensity of the tube with a visible light sensor 120 which is positioned downstream of the reflector 50. Referring to Fig. 11, visible scattered light is supplied to the visible light sensor 120 through the slots 122 (3) - 122 (5) behind each of the center tubes 10 (3) - 10 (5) on the reflector plate 50 slightly to the left of center. Voltage sensing circuit 210 signals the microcontroller 200 when timer 100 has initiated the down-counting sequence and also when the maximum allowable voltage of the starter has been reached. Using the signals from these sensors, the microcontroller 200 compares the current state of the device with the values ​​recorded during calibration and determines if the starter voltage needs to be adjusted. The regulation of the voltage of the starter is performed by a bank of electronic switches coupled through optocouplers 222, operating at the moment of the voltage crossing, with the output lines of the microcontroller. Finally, if the device is not functioning properly or is not producing radiation within the specified parameters, the microprocessor 200 activates the device status indicator 112 to inform the user thereof. The functional blocks of the electronic control system will now be described in more detail.

According to a preferred embodiment of the present invention, a fully programmable embedded microcontroller 200 (e.g., Microchip PLC16F84) is provided which includes an arithmetic logic unit, RAM, non-volatile RAM, ROM, and an interface circuit in a single monolithic integrated circuit. The microcontroller 200 also includes an electronically independent watch-dog timer that is programmed to reset the CPU to an initial state in the event of a hardware failure of the microcontroller or a firmware error. The microcontroller 200 interfaces with the device sensors, the device status display 112, and the set of electronic switches through twelve programmable digital I / O lines. The device calibration parameters are stored in the non-volatile RAM memory inside the microcontroller chip, and all the software used to control the controller functions is contained in the ROM memory inside the microcontroller chip. Firmware is written into ROM and verified using external programming devices.

According to a preferred embodiment of the present invention, a visible light sensor 120 (e.g., Texas Instruments TSL230B optical sensor) is used to detect tube emission and a signal from the visible light sensor 120 is used as an adjustment criterion. In the case of the TSL230B optical sensor, a large area photodiode and an integrated current to frequency converter provide an output signal to the microcontroller in the form of a series of digital pulses.

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Direct conversion of the optical signal to digital format reduces circuit complexity and eliminates the calibration and drift problems associated with analog circuits.

The visible light sensor 120 is provided behind the center tube 10 (4) and the reflector panel 50 slightly to the left of center. In order to monitor the pattern of visible light from the plurality of tubes, three slots 122 (3) - 122 (5) were made in the reflector 50 behind the three central tubes 10 (3) - 10 (5). The surface area and the position of the three slots 122 (3) - 122 (5) are such that the visible light sensor 120 receives an even intensity from the three tubes 10 (3) - 10 (5). According to a preferred embodiment of the present invention, the area ratio for any two selected slots is proportional to the reciprocal of the squares of the distance of the selected slots from the visible light sensor 120. The visible light sensor 120 is covered with a filter to match its spectral characteristics with those of the optometer that was used as the measurement standard for calibration. Additionally, the visible light sensor 120 is covered with a light diffuser to further minimize the detector position dependence on the gaps in the reflector 122 (3) - 122 (5).

The voltage sensing circuit 210 performs two functions: it coordinates the operation of the microcontroller with the system clock 100, and informs the microcontroller 200 when the maximum allowable voltage of the starter is reached. In a preferred embodiment of the present invention (referring to Fig. 9A), voltage detection circuit 210 comprises a CD4046 phase locked loop (PLL) circuit 214 used as a voltage controlled oscillator (VCO). The line voltage sample applied to the starter is rectified and used both to provide power to the CD4046 and as a VCO input.

This arrangement allows the circuit to generate a series of digital pulses whose frequency is proportional to the voltage of the starter. The pulse train is coupled through an optocoupler 212 to a microcontroller 200 which determines the voltage of the starter by measuring the time between pulses.

Detection of the state of the chip clock is accomplished by placing the clock relay contacts in series with the starter power terminals. When timer 100 is turned off (e.g., therapy is not being performed), no voltage is applied to either the voltage sensing circuit 210 or the pacemakers 20. Upon detecting this condition, the microcontroller 200 initializes system variables and loops until there are pulse train (voltage). After the timer has initiated the down-counting sequence, the clock relay contacts close by applying voltage to the voltage sensing circuit 210 and the starters 20. When the presence of the pulse train is detected by the microcontroller 200, it performs an adjustment (see below). Although the regulator circuit can regulate the voltage of the starter, the duration of the illumination is hardware-controlled by the timer 100 by connecting the relay contacts in series.

After visible light irradiation is initiated, the microcontroller 200 monitors the VCO pulse train and compares it with the value stored in memory during device startup and calibration. If the measured value exceeds the stored value, any further increase in the voltage of the starter is blocked. The value stored in the memory of the microcontroller corresponds to the starter voltage on one transformer tap, corresponding to a value lower than the maximum operating voltage, not allowing the selection of the transformer tap corresponding to the maximum voltage of the starter. This method minimizes unnecessary switching and ensures that the starter voltage does not exceed the maximum allowable operating voltage (133 VAC in the preferred embodiment of the present invention) at any time.

Referring to Figs. 9C and 9D, the electronic switch set for selecting the transformer tap includes six thyristor electronic switches 220 that connect the starter input lines and the voltage selection taps on the step-down and step-up autotransformers 60. The gates of the thyristor switches 220 are electro-optically coupled to the microcontroller 200. The microcontroller 200 thus increases or decreases the voltage applied to the starters 220 (increasing or decreasing tube emissions) by energizing the respective control gates to select the appropriate taps.

According to preferred embodiments of the present invention, the device status indicator 112 shows when the emitted radiation is abnormal when a device failure occurs. Measurements with a separate power meter are not necessary.

In one preferred embodiment of the present invention, the device status indicator 112 includes a single LED that indicates the functional state of the device with appropriate flashing.

Immediately after turning the key to the "ON" position for the first time, the LED flashes three times, indicating that the device is operating normally and is ready for use. If this does not happen, either the LED,

Either the microcontroller is malfunctioning, or the key switch 20 has been turned on, off and back on too soon for the microcontroller 200 to reset the LED control to its initial state. If the LED does not flash three times after turning the power off for several seconds and then turning it on again, the device should not be used.

Blinking rapidly immediately after ignition 90 is turned on indicates that a checksum error has occurred in the microcontroller 200. This may occur if there are problems with the values ​​stored in the microcontroller's memory for optical adjustment and starter voltage limitation. In this case, the device is not ready for operation and will not emit light.

If slow flashing occurs after the timer has been initiated and the controller tries unsuccessfully to reduce the tube's emission intensity 10 times to adjust the emission parameters to the set range, it means that the emission intensity may be too high and the starter voltage cannot be reduced further. This may be due to damage to the microcontroller or other component. If the LED blinks slowly during exposure, the exposure should be interrupted as the intensity of the emission may be higher than the specified maximum.

If the indicator is lit continuously after the irradiation has been initiated and the controller tries unsuccessfully to increase the tube emission intensity 10 times to the assumed values, it means that the emission intensity may be too low and the starter voltage cannot be increased further. If the LED is lit continuously during exposure, but does not flash, exposure may continue, although performance may be reduced due to the tube's low emission intensity. The LED will be blanked if the emitted radiation rises above a certain minimum value.

The microcontroller firmware has three main executive modules: power-up initialization, calibration and adjustment. Only power-on initiation modules and adjustments are made during patient illumination.

The power-up initialization module is only executed at microcontroller power-up, when the key 90 is inserted and turned to the "ON" position. During this time, the program variables are given their initial values ​​and the calibration values ​​stored in non-volatile RAM are restored. Additionally, a checksum calculation is performed and compared to the stored checksum value. In case of incompatibility, the software turns off the device and initiates fast LED blinking. After successful startup, control is transferred to the control module.

After the control module is actuated, the microcontroller 200 executes a voltage detection loop until it detects either a pulse train from the voltage circuit or the closure of contacts on one of the technician's accessible keys / jumpers. The loop determines the initial state of the internal clock and error flags. If contact closure is detected, control is transferred to the calibration module (see below). After the exposure time has been set on timer 100 and the "START" key 104 has been pressed, the microcontroller 200 detects the pulse train generated by the VCO and executes the main control loop. This starts an internal clock (independent of the chip clock). The main control loop reads the signals from the VCO, the visible light sensor 120 and the internal clock; a new tap relay is selected if necessary and possible device errors are displayed every three seconds according to the algorithm described below. Loop execution continues until the timer stops the illumination and the VCO pulse train.

After the timer first initiates a down-counting sequence, the microcontroller 200 sets a set of switches to apply line voltage to the starters 20. During the first 2.5 minutes (as measured by the internal clock), a visible light sensor 120 measures the tube's emission intensity and the appropriate transformer taps are selected to maintain the emission intensity at half the range defined by the minimum and maximum intensity recorded values (9, 3 and 10.7 mW / cm² according to a preferred embodiment of the present invention. This is done in order to provide optimal heating of the pipe while keeping the emission intensity within a predetermined value range.

In order to have sufficient time for the emission intensity to be within the preset value range five minutes after any regulation of the starter voltage, the microcontroller 200 switches the lower regulation limit to the stored value (9.3 mW / cm² in a preferred embodiment of the present invention) after the first two and a half minutes of operation; the upper limit remains unchanged. Since the control limits are not modified outside of this location, the output radiation will remain within these values ​​until the illumination is completed.

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If the radiation intensity cannot be kept between the regulation limits, the device error flags activate the device status indicator (LED). The device error is not reported until the system makes ten attempts to correct the parameters. This gives the pipes the time it takes for the pipes to respond to regulation and avoids signaling temporary outages.

During execution of each loop, the microcontroller 200 measures the starter voltage with the VCO and sets a lockout flag if the voltage has reached its maximum value. Although this action does not directly signal an error, an error can be signaled if the intensity emitted by the device is too low and cannot be increased by setting the lock flag. If timer 100 interrupts the irradiation, the pulse train from the VCO will run out and the microcontroller 200 will return to the voltage detection loop waiting for a new irradiation to be initiated.

The data for the calibration module is established before the device is installed in the clinic. The maximum allowable starter voltage for the voltage detection circuit 210 and the visible light sensor signals 120 corresponding to the lower and upper control limits are stored in the microcontroller's memory using an initialization / calibration algorithm.

In order to establish the maximum voltage of the starter, the voltage calibration jumper on the circuit board is closed, causing the microcontroller 200 to enter the voltage calibration mode. An autotransformer is used to adjust the starter voltage for a transformer tap giving a voltage lower than the maximum allowable starter voltage (127 VAC in the preferred embodiment of the present invention). When the voltage calibration jumper is closed again, this voltage and the checksum value are saved in the non-volatile memory of the microcontroller. Each time the voltage calibration jumper is closed, the Device Status Indicator (LED) will flash to indicate that the action has been completed.

Then, the upper and lower adjustment limits are saved in the memory of the microcontroller by switching to the optical calibration mode. A standard UDT optometer (eg, a UDT S370 power meter with 247 detectors and a cosine diffuser) is placed at the reference point. According to a preferred embodiment of the present invention, the reference point is 3 inches from the polycarbonate sheath 40 at the center of the therapeutically active space. The voltage of the starter is regulated by means of an autotransformer in order to obtain the desired maximum emission intensity at the readings of the optometer. The corresponding output from the visible light sensor 120 is stored in the microcontroller memory as the upper limit of the emission intensity.

The procedure is repeated with the emission intensity adjusted to obtain the desired minimum value of the optometer and to establish the lower control limit.

Finally, a checksum is written and the microcontroller 200 returns to executing the power-up initialization module resuming normal operation. As with voltage calibration, the Device Status Indicator (LED) blinks each time calibration data is saved.

It has been found that according to a preferred embodiment of the present invention, the measured emission intensity from the active emitting surface is approximately 70% of the measured maximum value when measured with a 4 inch and 2 inch cosine response detector and approximately 60% of the maximum value at all other operating distances. .

Examples of methods of diagnosis and therapy

An example of a method of treating precancerous lesions such as senile keratosis with PDT using an illuminator described above in combination with levulinic 5-amino acid (ALA) will now be described.

Substantially anhydrous ALA is mixed with a liquid diluent just prior to use. The ALA mixture is delivered topically to the lesions using a punctual dispenser to control the breakdown of the ALA mixture. A suitable dispenser is described in US Patent Application 08 / 962,294 (filed October 31, 1997) and ALA is also generally discussed in US Patent Application 08 / 921,664 (filed September 2, 1997). The entire content of these reports is incorporated herein by reference.

After the applied portion of the ALA mixture is dry, one or more additional portions may similarly be applied. About 2 mg / cm is prescribed² ALA. The formation of photosensitive porphyrin and sensitization to light of the treated lesions occurs within the next 14-18 hours, during which time exposure to direct sunlight or other bright light source should be minimized. Between 14 and 18 hours after administering ALA, the lesions are illuminated

With an illuminator according to the present invention. The illuminator illuminates the lesions with homogeneous, blue light for the prescribed time. According to a preferred therapy, visible light has a nominal wavelength of 417 nm.

Since the total light dose (J / cm²) = illumination intensity (W / cm²) x time (s), the only additional parameter that should be controlled in order to deliver the light dose for the appropriate therapy is the exposure time. This is done in a preferred embodiment of the present invention by a timer which controls the electrical energy to the pacemakers and which can be set by the physician. The data shows that 10 J / cm² supplied from a source with a radiation intensity of 10 mW / cm² gives clinically satisfactory results. According to the above equation, this light dose requires an exposure time of 1000 seconds (16 minutes, 40 seconds). The selected dose of light can also be administered by additionally or alternately changing the intensity of the illumination.

Additional advantages and modifications will be apparent to those skilled in the art. Thus, the invention, in its broader aspect, is not limited to the details given and the exemplary devices shown and described herein. Accordingly, various modifications can be made without departing from the idea and letter of the general inventive concept as defined by the appended claims and their equivalents.