Abstract:
An apparatus for irradiating a specimen: that includes an optical transmitter for transmitting light from a laser source; an optical probe configured to receive the light from the optical transmitter and to apply the light upon emission from an optical exit to the specimen; a position detector adapted to detect a position of the optical probe in a longitudinal direction and to output a signal indicative of the position or of a change in the position relative to a surface forward of the optical probe; a drive coupled to the optical probe and adapted to controllably adjust a position of the optical probe in the longitudinal direction; and a feedback controller adapted to receive the signal from the position detector and to control the drive to control the position to keep the optical probe at substantially a constant position relative to the surface forward of the optical probe.

Description:
FIELD OF THE INVENTION 
       [0001]    The present invention relates to an irradiation method and apparatus, of particular but by no means exclusive application in ablating tissue, and especially soft tissue (such as the retina, vessel wall, trabecular meshwork, or other tissue), in a liquid environment. 
       BACKGROUND OF THE INVENTION 
       [0002]    Infrared sources, such as CO2, erbium-YAG and holmium:YAG lasers, have undergone trials, involving optical fiber delivery to a surgical target. Though adapted for use in intraocular surgery, problems include collateral, thermal damage to surrounding tissue and shock-wave effects. 
         [0003]    UV lasers are widely accepted for use in corneal refractive surgery, such as photorefractive keratectomy (PRK) and laser intrastroma keratomileusis (LASIK), and provide good control of ablation depth and minimal damage to surrounding tissue. However, such systems are adapted for use in gaseous environments—that is, typically the atmosphere. 
         [0004]    UV lasers at 266 nm have been extensively studied for use in tissue ablation in liquid environments; they are closely matched to the absorption peak of proteins in some target tissues and afford good control of ablation depth with minimal damage to surrounding tissue. 
         [0005]    UV lasers at 213 nm have also been extensively studied for use in tissue ablation in liquid environments. They allow good control of ablation depth and minimal damage to surrounding tissue, but provide poor penetration in liquids. For example, the absorption coefficient (a) depends on the nature and contents of the liquid, which change according to disease and disease advancement, and liquid concentrations: both can be difficult to estimate clinically. For example, absorption coefficient differs from 0.05 to 6.9 cm −1  for 0.9% saline and BSS (Balanced Salt Solution, respectively. 
         [0006]    In addition, in UV lasers are often controlled to deliver multiple pulses. However, each pulse produces a certain amount of tissue ablation, thereby changing the distance between illuminating probe and the tissue and the contents and nature of the surrounding liquid. This results in a continually changing surgical environment. 
         [0007]    One existing approach is illustrated schematically in  FIG. 1  at  10 , which shows an optical probe  12  for applying ultraviolet light  14  from a laser source (not shown) to a specimen  16 —being an irradiated portion of a biological tissue in this example—in a liquid  18 . Other portions of the tissue may not be in contact with liquid  18 , but specimen  16  is regarded as in a liquid because liquid  18  and specimen  16  have an interface  20 . 
         [0008]    The forward or distal end  22  of optical probe  12  is tapered to a distal tip  24 , which is also the exit from which the ultraviolet light  14  is emitted from optical probe  12 . In use, there is a liquid layer  26  of the liquid  18  between distal tip  24  and specimen  16 , and hence there is also an interface  28  between liquid  18  and distal tip  24 , corresponding essentially to distal tip  24 . 
         [0009]    In use, ultraviolet light  14  is applied to specimen  16  in order to ablate specimen  16  (that is, remove surface portions of specimen  16 ). This leads, however, to the irradiation of liquid  18  in liquid layer  26  between distal tip  24  and specimen  16 , causing changes to its composition, temperature and absorption coefficient. The ablation of specimen  16  also progressively increases the distance between the optical probe  12  and specimen  16 , and the material removed by ablation further alters the composition of liquid  18  and hence its absorption coefficient. 
         [0010]    Thus, liquid layer  26  between the optical probe  12  and the specimen  16  constitutes a complicated and unpredictable boundary, requiring consideration of (and potentially allowance for) micro-irradiation effects, laser biophysics, laser chemistry, laser biochemistry and probe-specimen distance, precluding a constant operational environment. 
       SUMMARY OF THE INVENTION 
       [0011]    According to a first broad aspect, the present invention provides an apparatus for irradiating a specimen (such as to ablate the specimen), the apparatus comprising:
       an optical transmitter for transmitting light (such as ultraviolet light) from a laser source;   an optical probe with an optical exit, the optical probe configured to receive the light from the optical transmitter and to apply the light upon emission from said exit to the specimen;   a position detector (such as a force or other transducer or a detector) adapted to detect a position of the optical probe in a longitudinal (that is, z-axis or forward/reverse) direction and to output a signal indicative of said position or of a change in said position relative to a surface forward of the optical probe;   a drive coupled to the optical probe and adapted to controllably adjust a position of said optical probe in the longitudinal direction; and   a feedback controller adapted to receive the signal from said position detector (whether subsequently processed or not) and to control said drive to control said position to keep the optical probe at substantially a constant position relative to the surface forward of the optical probe.       
 
         [0017]    Generally, the optical probe is adapted to be located when in use with the exit in contact with the specimen, in which case the material forward of the optical probe is the specimen. 
         [0018]    Thus, the distance between optical probe and the surface (such as the specimen) affects, for example, ablation, so is thus advantageously controlled according to this aspect to be substantially constant. The present invention maintains the distance as effectively zero, which both is simpler to maintain and minimizes the effects of liquid—if used in a liquid environment—between probe and specimen (in those embodiments in which the surface is the specimen). It is expected that, although some liquid may be trapped between the probe and specimen, it will i) be minimal, and ii) be promptly evaporated during use, further reducing its quantity. 
         [0019]    Thus, a generally gentle contact can be maintained between tip and specimen. 
         [0020]    Although the apparatus is envisaged as principally for use for ablation, it could alternatively be incorporated into a fiberoptic laser endoscope and used to irradiate, for example, tumors (such as of the trachea, oesophagus or stomach). Such an endoscope typically comprises separate optical channels—terminating in the endoscope head—for imaging and specimen irradiation (according to this invention), respectively. 
         [0021]    The optical probe could be, for example, solid or capillary, but is typically in the form of an optical fiber or an optical fiber bundle of optical fibers, such that the exit comprises the exit tip of the optical fiber or the exit tips of the optical fibers of the optical fiber bundle, respectively. 
         [0022]    In one embodiment, the exit is at a distal tip of the optical probe and configured to emit the light in the longitudinal direction. 
         [0023]    In one embodiment, the position detector comprises a force transducer coupled to the optical probe, wherein the force transducer is arranged to output a signal indicative of a force or a change in force between the optical probe and the surface, the feedback controller is adapted to output to the drive a control signal determined from the signal and the drive is adapted to receive the output signal and to control the position so as to maintain a substantially constant force between the optical probe and the surface (such as the specimen). 
         [0024]    In another embodiment, the position detector comprises a probe adjacent to or coupled to the optical probe and having a force transducer, wherein the probe is arranged to contact the surface, in use, and output a signal indicative of a force or a change in force between the probe and the surface, the feedback controller is adapted to output to the drive a control signal determined from the signal and the drive is adapted to receive the output signal and to control the position so as to maintain a substantially constant force between the optical probe and the surface. 
         [0025]    The apparatus may include a laser source for supplying the laser light. In applications in which the light is ultraviolet light, the laser source may comprise an ultraviolet laser source, or an infrared laser source and a mechanism for converting an output of the infrared laser source into ultraviolet light. 
         [0026]    In another particular embodiment, the exit is located to emit the light laterally from the optical probe so as to irradiate the specimen when located beside the optical probe. The probe may be adapted to direct the light to exit the exit by reflecting the light towards the exit (such as with a mirror located in the probe, which may operate conventionally or by total internal reflection). 
         [0027]    According to a second broad aspect, the present invention provides an endoscope comprising the apparatus described above. 
         [0028]    According to a third broad aspect, the present invention provides an ablation apparatus comprising the apparatus described above. 
         [0029]    According to a fourth broad aspect, the present invention provides a method of irradiating a specimen (such as to ablate the specimen), the method comprising:
       locating an optical probe having an exit with the exit in contact with the specimen;   transmitting light (such as ultraviolet light) from a laser source to the optical probe; and   applying the light upon emission from the exit to the specimen;   detecting a position of the optical probe in a longitudinal direction with a position detector;   outputting from the position detector a signal indicative of the position or of a change in the position relative to a surface forward of the optical probe; and   controlling a drive coupled to the optical probe to control the position to keep the optical probe at substantially a constant position relative to the surface forward of the optical probe.       
 
         [0036]    In one embodiment, the method includes driving the optical probe to maintain a position of the exit against the surface. 
         [0037]    The method may include employing a feedback controller to control the drive according to the signal. 
         [0038]    In another particular embodiment, the method includes emitting the light laterally from the optical probe and thereby irradiating the specimen located beside the optical probe. The method may include directing the light to exit the exit by reflecting the light towards the exit (such as with a mirror located in the probe, which may operate conventionally or by total internal reflection). 
         [0039]    According to a fifth broad aspect, the present invention provides a method of ablating a specimen, comprising the method described above. 
         [0040]    It should be noted that any of the various features of each of the above aspects of the invention, and of the various features of the embodiments described below, can be combined as suitable and desired. 
     
    
     
       BRIEF DESCRIPTION OF THE DRAWING 
         [0041]    In order that the invention may be more clearly ascertained, embodiments will now be described, by way of example, with reference to the accompanying drawing, in which: 
           [0042]      FIG. 1  is a schematic view of an optical probe for applying ultraviolet light to a specimen according to the background art; 
           [0043]      FIG. 2  is a schematic view of a laser ablation system according to an embodiment of the present invention; 
           [0044]      FIG. 3  is a schematic view of the optical probe for applying ultraviolet light to a specimen of the system of  FIG. 2 ; 
           [0045]      FIG. 4  is a schematic view of the optical probe for applying ultraviolet light to a specimen of the system of  FIG. 2 ; 
           [0046]      FIGS. 5A and 5B  are schematic views of the optical probe of  FIG. 4  in use; 
           [0047]      FIGS. 6A to 6C  are schematic views of optical probes according to other embodiments of the present invention, for use in variants of the system of  FIG. 2 . 
       
    
    
     DETAILED DESCRIPTION 
       [0048]      FIG. 2  is a schematic view of a laser ablation system according to an embodiment of the present invention. System  30  includes a Nd:YAG infrared laser source  32  that emits infrared light at 1064 nm. In the exemplary application described herein, for ablating a lesion, Nd:YAG infrared laser source  32  is controlled to deliver 1 to 100 pulses of light, each of 0.4-0.7 J/cm 2  and 4-6 ns duration, a pulse repetition rate of 10 Hz, a beam diameter of 6 mm, and a beam divergence of 0.6 mrad. 
         [0049]    System  30  also includes a pair of mirrors  34   a , 34   b  that reflect the infrared light into a harmonic generator  36  that emits the infrared light as well as light at harmonic wavelengths 532 nm, 266 nm and 213 nm. Harmonic generator  36  comprises BBO crystals for generation of the second harmonic and CLBO crystals for generation of the fourth (266 nm) and fifth (213 nm) harmonics. 
         [0050]    System  30  includes a dispersing prism  38  that receives the light emitted by the harmonic generator  36  and emits it dispersed according to wavelength, and first and second beam blocks  40  and  42  located to receive and block from further transmission the 1064 nm and 532 nm wavelength beams of light. 
         [0051]    System  30  also includes moveable third and fourth beam blocks  44  and  46 , and partially reflective mirrors  48  and  50 . Third and fourth beam blocks  44  and  46  are locatable respectively in the optical paths of the 266 nm and 213 nm wavelength beams of light. A drive mechanism (not shown) allows third and fourth beam blocks  44  and  46  separately to be controlled to selectively pass or block each of these beams of light, and—when passed—these 266 nm and 213 nm wavelength beams impinge partially reflective mirrors  48  and  50 , respectively. 
         [0052]    Light at 266 nm and 213 nm closely matches absorption peaks of proteins in specimens of the type described below, but in other applications different wavelengths may be preferable and hence employed as necessary and suitable. 
         [0053]    System  30  includes a hollow glass taper  52  for concentrating the beam, towards the larger (or entrance) end of which partially reflective mirrors  48  and  50  direct the reflected component of the 266 nm and 213 nm wavelength beam(s). Taper  52  is coupled at its distal or narrow end to the proximal end of an optical probe  54  (comprising an optical fiber, as described below) and thus launches the beam into the proximal end  56  of optical probe  54 . The distal end of optical probe  54  is locatable against a specimen (in this example, an intraocular specimen, such as a portion  58  of is the retina of an eyeball  60 ). 
         [0054]    It should be noted that, in system  30  (and other embodiments of the present invention) light may be transmitted by any suitable mechanism or medium. For example, some or all of the optical paths referred to above or shown in  FIG. 2  may comprise free space, an optical transmitter such as an optical fiber or fiber bundle, or any suitable combination of these. 
         [0055]    Thus, system  30  can be employed to irradiate and ablate specimen  58  with an ablating beam of wavelength 266 nm or 213 nm, or with components of wavelength 266 nm and of wavelength 213 nm. 
         [0056]    System  30  includes a rotatable prism  62  located in the optical path between dispersing prism  38  and partially reflective mirror  50 , which is rotatably adjustable so that the path of the 213 nm beam can be finely adjusted. 
         [0057]    System  30  also includes a second laser source in the form of HeNe laser source  64 , which emits visible light with a wavelength of 633 nm. Additional mirror pair  66   a,    66   b  direct light from HeNe laser source  64  through partially reflective mirrors  48  and  50  (and hence into the same optical path as that of the ablating light) onto the specimen  58 . This visible light allows, in effect, the visualisation of the location of incidence of the ablating beam (which, being in the ultraviolet, is invisible to the naked eye). 
         [0058]      FIG. 3  is a schematic view of the optical probe of system  3  of  FIG. 2 , shown generally at  70 , for applying ultraviolet light to specimen  58 . Optical probe  70  is comparable to optical probe  12  of  FIG. 1 , and comprises an optical fiber of 800 mm length and 200 μm core diameter with a tapered forward or distal end  72  that is tapered to a distal tip  74  with a 60 μm diameter core. This core is also the exit from which ablating ultraviolet light and visualizing visible light are emitted from optical probe  70 . In use, distal tip  74  is immersed in a surrounding liquid  76  and located in contact with specimen  58 . 
         [0059]    In use, distal tip  74  is located against specimen  58  (as is described in greater detail below). In use, optical probe  70  ablates a hole in the specimen of approximately 60 μm diameter, and from 40 to 400 μm depth depending on whether the optical probe  70  is not advanced or is advanced, respectably, between pulses. 
         [0060]    Referring again to  FIG. 3 , system  30  includes a feedback control mechanism that includes a transducer  78  in the form of a force transducer, coupled to the optical probe  70  towards the proximal end  80  of optical probe  70  and hence, in use in this example, located outside eyeball  60 . Transducer  78  is essentially responsive to longitudinal movement in the position of optical probe  70 , and configured to output a signal indicative of a force, or change in force, caused by such longitudinal movement. The feedback control mechanism of system  30  also includes a feedback controller  84  and a drive  86  coupled to optical probe  70  for moving optical probe  70  in a longitudinal direction. Output signal  82  is transmitted to feedback controller  84 , which generates a control signal  88  for drive  86  adapted to control drive  86  to drive optical probe  70  so as to restore the force (or eliminate the change in force) detected by transducer  78 . 
         [0061]    Thus, once optical probe  70  has been located as desired against the specimen  58 , such that distal tip  74  exerts a gentle force against specimen  58 , this feedback control mechanism—comprising transducer  78 , feedback controller  84  and drive  86 —is activated and holds distal tip  74  against the specimen  58  so that the original gentle force is maintained. 
         [0062]      FIG. 4  is a schematic view of the optical probe  90  for use in a variation of system  30  to apply ultraviolet light to specimen  58 , according another embodiment of the present invention. Optical probe  90  is identical in many respects with optical probe  70  of  FIG. 3 , and like reference numerals have been sued to identify like features. However, in this embodiment optical probe  90  is provided with a feedback control mechanism having a transducer  92  in the form of an optical sensor. Transducer  92  is located to receive a portion  94  of the light transmitted from specimen  58 , hence providing an output signal  96  that is a measure of the level of contact between distal tip  74  and specimen  58  (as removal of distal tip  74  from specimen  58  will reduce the intensity of return light captured by distal tip  74  and transmitted to transducer  92 ). Feedback controller  98  of this embodiment uses this signal  96  to generate a control signal  100  for drive  86  adapted to control drive  86  to drive optical probe  70  so as to restore the intensity of return light detected by transducer  92 . Thus, in this embodiment the position of the distal tip  74  in gentle contact with specimen  58  is preserved, by a feedback control mechanism comprising transducer  92 , feedback controller  98  and drive  86 . 
         [0063]    It will also be appreciated that the feedback control mechanism of  FIGS. 3 and 4  could, in another embodiment, both be employed in the one system. This would allow the use of feedback based on two simultaneous measures of the position of the distal tip. 
         [0064]      FIGS. 5A and 5B  illustrate the placing of optical probe  70 , 90  into the appropriate location for ablation of specimen  58 , which—as described above—comprises in this example a portion of the retina of an eyeball  60 . Referring to  FIG. 5A , the leading or distal portion of optical probe  70  is located inside a 25G needle  110 , which is used to penetrate the wall  112  of eyeball  60  through the pars plana or other location, according to target specimen/tissue. 
         [0065]    Referring to  FIG. 5B , optical probe  70  is then advanced inside eyeball  60  until in gentle contact with and just touching specimen  58 . This contact can be judged by visualisation under an operating microscope or endoscope. Alternatively, the degree of contact with specimen  58  can be assessed by monitoring an output signal from transducer  78  or  92  (according to the embodiment) or from feedback controller  84  or  98 , to ensure that distal tip  74  tip just touches the specimen  58 . The feedback control mechanism is then employed to maintain the longitudinal position of optical probe  70  as described above. The position of optical probe  70  in other directions is maintained by conventional techniques. 
         [0066]      FIGS. 6A to 6C  are schematic views of optical probes according to other embodiments of the present invention, for use in variants of the system of  FIG. 2  with specimens that are laterally adjacent the distal tip of the respective optical probe. 
         [0067]    These embodiments would typically be preferred when the specimen or target tissue is adjacent to normal tissue, and it is desired to protect the normal tissue. 
         [0068]      FIG. 6A  is a schematic view of an optical probe  120  according to an embodiment of the present invention in use with a specimen  122  that is itself adjacent to normal tissue  124 . In this embodiment, optical probe  120  is not tapered, but instead includes a 45° mirror  126  at the distal end of optical probe  120  that deflects incoming light 90° so that it is emitted from an exit into a specimen laterally adjacent optical probe  120 . The ablating irradiation is therefore not directed towards the normal tissue  124 , which in the configuration of optical probe  70  of  FIG. 3  might pass through the specimen  122  and into normal tissue  124  below (in this view) specimen  122 . 
         [0069]    Mirror  126  may be provided in any suitable way, such as by providing optical probe  120  with an oblique distal tip with a silvered surface, or an internal, mirrored surface. 
         [0070]      FIG. 6B  is a schematic view of an optical probe  130  according to another embodiment. Optical probe  130  is comparable to optical probe  120 , except that—instead of a 45° mirror—optical probe  130  has a mirror  132  that deflects light through an obtuse angle and hence somewhat upwardly (in this view), such as by 100° or 110°. Thus, specimen  122  may be irradiated even though somewhat further above the normal tissue  124  than in the example shown in  FIG. 6A . 
         [0071]      FIG. 6C  is a schematic view of an optical probe  140  according to still another embodiment. Optical probe  140  is again comparable to optical probe  120 , except that—instead of a 45° mirror—optical probe  140  has a mirror  142  that deflects light through an acute angle and hence somewhat downwardly (in this view), such as by 70° or 80°. Thus, specimen  122  may be irradiated even though closer to normal tissue  124  than in the example shown in  FIG. 6A . 
         [0072]    In each of the embodiments of  FIGS. 6A to 6C , the feedback control mechanism comprises a force transducer (as described above by reference to  FIG. 3 ), and controls the respective optical probes to maintain position relative to normal tissue  124 , and hence relative to specimen  122 . 
         [0073]    Modifications within the scope of the invention may be readily effected by those skilled in the art. It is to be understood, therefore, that this invention is not limited to the particular embodiments described by way of example hereinabove. 
         [0074]    In the claims that follow and in the preceding description of the invention, except where the context requires otherwise owing to express language or necessary implication, the word “comprise” or variations such as “comprises” or “comprising” is used in an inclusive sense, that is, to specify the presence of the stated features but not to preclude the presence or addition of further features in various embodiments of the invention. 
         [0075]    Further, any reference herein to prior art is not intended to imply that such prior art forms or formed a part of the common general knowledge in Australia or any other country.