Abstract:
A handheld confocal imaging system for in vivo observation of dermal and subdermal tissue allows diagnosis of conditions substantially beneath the surface of the skin. A confocal head has optics which scan the tissue so as to provide images of vertical sections of the tissue. Both two and three dimensional imaging may be provided for diagnosis and location of basal cell carcinomas and melanomas, and so as to enable visualization of tumor borders prior to excision.

Description:
[0001]     This application claims the priority benefit of co-pending provisional application, Ser. No. 60/001,141, filed Jul. 13, 1995. 
     
    
     FIELD OF THE INVENTION  
       [0002]     The present invention relates to handheld confocal imaging system for in vivo clinical examinations of dermal and subdermal tissues using non-ionizing radiation, and particularly laser radiation which is of a wavelength capable of penetrating into the skin.  
         [0003]     The invention is especially suitable for providing an instrument for dermal pathology applications. The invention is also applicable for visualizing sections in other scattering media than tissue. The invention enables the use of a laser as a source of illumination. The instrument may provide data to image processing computers, which may be programmed to provide high resolution images of dermal sections.  
       BACKGROUND OF THE INVENTION  
       [0004]     Systems have been proposed for viewing the surface areas of the skin or the external surfaces of internal tissue. Viewing without scanning is described in Pennypacker, U.S. Pat. No. 4,817,622, issued Apr. 4, 1989. Examination of internal tissue surfaces by means of beam scanning are proposed in Harris, U.S. Pat. No. 5,120,953, issued Jun. 9, 1992, Ohki, U.S. Pat. No. 5,122,653 issued Jun. 16, 1992, Webb, U.S. Pat. No. 4,768,874 issued Sep. 6, 1988 and Pflibsen, U.S. Pat. No. 4,991,953 issued Feb. 12, 1991. Such proposals have not provided a handheld instrument which is readily usable by a surgeon in clinical examinations for imaging the epidermis and dermis, especially in vertical sections or in horizontal sections at desired depths below the surface of the skin.  
       SUMMARY OF THE INVENTION  
       [0005]     Accordingly, it is the principal object of the present invention to provide and improve clinical dermatological imaging system.  
         [0006]     It is another object of the invention to provide an improved confocal imaging system which provides images of dermatological tissues and avoids the need for biopsies to detect the location of such abnormalities as basal cell carcinomas and melanomas.  
         [0007]     It is a still further object of the present invention to provide an improved confocal dermatological imaging system which does not require ionizing radiation and may use a laser beam.  
         [0008]     It is a still further object of the present invention to provide an improved confocal imaging system which provides in vivo imaging of dermatological tissue both at and below the skin and which may be handheld and which is capable of operating in various scattering media.  
         [0009]     It is a still further object of the present invention to provide an improved confocal dermatological imaging system which may use a computer to generate images from data produced by the optics which provides confocal imaging and to display or provide images for further evaluation or computer enhancement. 
     
    
     BRIEF DESCRIPTION OF THE DRAWINGS  
       [0010]     The foregoing objects, features and advantages of the invention will become more apparent from a reading of the following description in connection with the accompanying drawings in which:  
         [0011]      FIG. 1  is schematic diagram of a confocal imaging system embodying the invention;  
         [0012]      FIG. 1   a  is a plan view of the head of the system shown in  FIG. 1 ;  
         [0013]      FIG. 2  is a block diagram of the system shown in  FIG. 1 , and especially the computer control and imaging system for acquisition and processing of the optical image;  
         [0014]      FIG. 3  is a schematic diagram of the handheld confocal imaging system of  FIG. 2  in use. 
     
    
     DETAILED DESCRIPTION OF THE INVENTION  
       [0015]     Referring to  FIG. 1  there is shown a system  10  for in vivo diagnosis of dermatological tissues. The system  10  may be embodied in a handheld head  32  as shown in  FIG. 1   a  and schematically in  FIG. 3 .  
         [0016]     Referring more particularly to  FIG. 1  there is shown a system  10  (or instrument) which contains optics of the type which are used in optical data storage heads which are used in recording and reading optical disks. Light from a laser diode, contained in a laser and collimator assembly  12 , is collimated by a diffraction limited lens in the assembly  12  and is incident at an oblique angle on a beam splitter assembly  14 . Refraction at this oblique angle causes the elliptical laser diode beam to become circular in cross-section. The circular beam passes through the beam splitter assembly  14  and a quarter wave plate  16  and is focused into the tissue  22  via a contact window  20  (a glass window plate) spaced from the sample, specimen or tissue  22  being examined, preferably by an optical contact liquid  21 . In the event the sample is viscus or liquid, it may be located in a sample well (not shown).  
         [0017]     The circular beam which passes through the beam splitter assembly  14  and the quarter wave plate  16  is focused into the sample by a precision focusing lens  18 , which suitably has a numerical aperture of 0.5 and a focal length of 4.3 millimeters. These dimensions and parameters are exemplary and demonstrate that the optical system  10  may be miniaturized so as to be adapted to be handheld.  
         [0018]     The quarter wave plate  16  converts the incident linear polarization from the laser in assembly  12  to circular polarization, i.e., the quarter wave plate is oriented 45° to the incident polarization. In other words, the beam from plate  16  is circularly polarized. The focusing lens  18  is movable both in a direction along its optical axis and laterally as indicated by the arrows  24  and  25 , respectively. Position mechanical actuators  34  ( FIG. 1   a ) may be used for moving the lens  18 , and thereby control position of the focus spot of beam in the sample. These actuators  34  may be similar to those used in optical disk systems. The lens  18  may be mounted on a pair of such mechanical actuators. The actuators  34  provide lateral and vertical scanning of the focused laser beam in the tissue sample.  
         [0019]     The focusing lens  18  also collects scattered light reflected from the sample. The amount of coherent light scattered back into the detection system (which includes lens  18 , plate  16  and assembly  14 ) depends upon local variations of the refractive index and the absorption in the immediate neighborhood of the focus spot. This coherent light may be defined as the component of the reflected light having a circular polarization orthogonal to the polarization of the beam focused into the tissue sample. The scattered light is incident to plate  16  and then to beam splitter assembly  14 . The plate  18  converts the coherent component of the scattered light into linear polarization, where beam splitter assembly  14  directs by reflection (or filters) the coherent light component of the scattered light at the beam splitting surface  15  in the beam splitter assembly  14 . The reflected light passes through a relay lens  26 . The light from relay lens  26  may be reflected from a pair of fold mirrors  28  (See also  FIG. 1   a ). These fold mirrors  28  may be part of the beam splitter assembly  14 . The relay lens  26  may also be part of this assembly  14 .  
         [0020]     The scanned light from the focus spot is reflected from the fold mirrors  28  to a pinhole photodetector assembly  30 , which may also be considered part of the detection system. The fold mirrors  28  are used to make the instrument more compact. A prism assembly may alternatively be used, which is part of the beam splitting assembly  14 , and allows the samples to be placed face down. This orientation allows gravity to assist in maintaining the sample in a stable viewing position. Maintaining a stable viewing position is also enhanced by the use of the window  20  as shown in  FIG. 1 .  
         [0021]     A top view of the instrument is illustrated in  FIG. 1   a.  Typical dimensions are given in  FIG. 1   a  to illustrate the compacted size of the confocal imaging head  32 . The elements in the head  32  may be located on a single board to provide unitized construction. The height of the head may be approximately two inches from the base to the nominal focal point of the focusing lens  18 .  
         [0022]     By scanning using the mechanical actuators  34  successive lines may be scanned at successive depths to provide images of vertical sections (i.e., along a vertical plane through the tissue sample). If desired the images may be formed from horizontal sections (i.e., along a horizontal plane through the tissue sample) as the lines are scanned horizontally. By tilting the sample, sections at desired angles to the surface of the sample (i.e., along a tilted or non-perpendicular plane) may be formed, such sections may also be formed by moving the lens  18  via actuator  34  as desired angles.  
         [0023]     Referring to  FIG. 2 , there is shown a block diagram of the data acquisition and analysis system which is part of the imaging system  10  provided by the invention. The confocal head  32  is the head shown in  FIGS. 1 and 1   a.  The output  36  from the head  32  is the output from the pinhole detector assembly  30 . This output  36  is the confocal detector signal. Signals are also provided from sensors  38 , namely a lateral position sensor and a vertical position sensor. These signals after amplification and filtering are acquired by a analog to digital converter of a digital I/O board  40 . This board  40  may also be on a board with a circuit which provides a digital to analog channel to drive the lateral motion actuator. The vertical scanning actuator is driven from a signal derived from a conventional signal generator  42 . The A to D, D to A and digital I/O board  40  is controlled and data is acquired via software in a personal computer  44 , such as a Macintosh Quadra 950. Conventional software packages may be used for image analysis and for driving a display  46 , which is shown by way of example as a 1472 by 1088 pixel display.  
         [0024]     Referring to  FIG. 3 , there is shown the confocal imaging head  32  contacted against the skin  48  of a subject specimen using a mineral oil as an optical index matching fluid, which is an optical contact liquid  21  ( FIG. 1 ) for reducing undesired reflections of light from the surface of the skin. The force against the skin  48  will be limited to that required to press the skin against the contact window  20  of the head  32 . A laser beam  50  which may be relatively low power (e.g., 6.3 milliwatts of optical power) is focused into the dermis of the specimen. The laser is operated at a wavelength capable of penetrating into the skin of the specimen, thus the skin may be considered transparent to the laser wavelength (or in other words, the skin is permeable to electromagnetic radiation of specified frequencies). The depth of focal point or spot  52  is varied from the surface of the stratum corneum to a few millimeters below the surface of stratum corneum. The nominal beam spot size may be, for example, 2.5 micrometers, full width half maximum. The laser spot is scanned laterally across the skin, for example at a rate of 3 to 10 hz. Different laser wavelengths may be selectively used for different resolution. Inasmuch as the energy delivered is proportional to the illuminating flux focused divided by the diameter of the spot, the scan length and the scan rate or frequency, the amount of incident flux is sufficiently low that damage to the specimen is avoided. The light scattered by the tissue is collected and the lights coherent component is re-imaged onto the pinhole aperture  54  of assembly  30 , as shown in  FIGS. 1 and 1   a.  The pinhole  54  transmits the coherent light from the focal region of the incident beam  53  to the detector  55  (of assembly  30 ) where it converts the light into an electrical signal. As the lens  18  scans laterally, the electrical signal is acquired by the computer and stored. Each scan represents a one dimensional trace of the reflectivity and scattering cross section of the dermis at a given level below the surface of the skin  48 . A series of scans are made with the focal point positioned at progressively lower depths thereby providing a vertical cross section image of the skin which may be similar to a B-scan ultrasound image. As stated earlier, these scans may also be horizontal to provide a horizontal cross-section, or at an angle to provide an angular cross-section of the skin.  
         [0025]     From the foregoing description it will be apparent that there has been provided an embodiment of a confocal imaging system for dermatological pathology applications. Variations and modifications of the herein described system and other applications for the invention will undoubtedly suggest themselves to those skilled in the art. Accordingly, the foregoing description should be taken as illustrative and not in a limiting sense.