Successful treatment of cancer is highly dependent on the stage at which it is diagnosed. Early diagnosis, when the disease is still localized at its origin, results in very high cure rates-even for cancers that typically have poor prognosis. Biopsies are often used for diagnosis of disease. However, because biopsies are destructive, only a limited number can be taken. This leads to reduced sensitivity for detection due to sampling error. A real-time fluorescence confocal microlaparoscope has been developed that provides instant in vivo cellular images, comparable to those provided by histology, through a nondestructive procedure. The device includes an integrated contrast agent delivery mechanism and a computerized depth scan system. The instrument uses a fiber bundle to relay the image plane of a slit-scan confocal microlaparoscope into tissue. It has a 3-µm lateral resolution and a 25-µm axial resolution. Initial in vivo clinical testing using the device to image human ovaries has been done in 21 patients. Results indicate that the device can successfully image organs in vivo without complications. Results with excised tissue demonstrate that the instrument can resolve sufficient cellular detail to visualize the cellular changes associated with the onset of cancer.
We describe the design and operation of a multispectral confocal microendoscope. This fiber-based fluorescence imaging system consists of a slit-scan confocal microscope coupled to an imaging catheter that is designed to be minimally invasive and allow for cellular level imaging in vivo. The system can operate in two imaging modes. The grayscale mode of operation provides high resolution real-time in vivo images showing the intensity of fluorescent signal from the specimen. The multispectral mode of operation uses a prism as a dispersive element to collect a full multispectral image of the fluorescence emission. The instrument can switch back and forth nearly instantaneously between the two imaging modes (less than half a second). In the current configuration, the multispectral confocal microendoscope achieves 3-µm lateral resolution and 30-µm axial resolution. The system records light from 500 to 750 nm, and the minimum resolvable wavelength difference varies from 2.9 to 8.3 nm over this spectral range. Grayscale and multispectral imaging results from ex-vivo human tissues and small animal tissues are presented.
We have developed a mobile confocal microendoscope system that provides live cellular imaging during surgery
to aid in diagnosing microscopic abnormalities including cancer. We present initial clinical trial results using the
device to image ovaries in-vivo using fluorescein and ex-vivo results using acridine orange. The imaging catheter
has improved depth control and localized dye delivery mechanisms than previously presented. A manual control
now provides a simple way for the surgeon to adjust and optimize imaging depth during the procedure while a
tiny piezo valve in the imaging catheter controls the dye delivery.
A mobile confocal microendoscope for use in a clinical setting has been developed. This system
employs an endoscope consisting of a custom designed objective lens with a fiber optic imaging bundle to
collect in-vivo images of patients. Some highlights and features of this mobile system include frame rates
of up to 30 frames per second, an automated focus mechanism, automated dye delivery, clinician control,
and the ability to be used in an area where there is a single 110V outlet. All optics are self-contained and
the entire enclosure and catheter can be moved between surgical suites, sterilized and brought online in
under 15 minutes. At this time, all data have been collected with a 488 nm laser, but the system is able to
have a second laser line added to provide additional imaging capability. Preliminary in vivo results of
images from the ovaries using topical fluorescein as a contrast agent are shown. Future plans for the system include use of acridine orange (AO) or SYTO-16 as a nucleic acid stain.
We previously reported on the development and testing of a multi-spectral confocal microendoscope. Here we present a
new system that will be used during an early stage clinical trial. The new microendoscope is significantly smaller, uses
fewer optical elements, and is structurally more robust. The slit-scanning confocal system employs two synchronized
single-axes scan mirrors and an externally coupled imaging catheter with automated focus control and dye delivery
systems. In grayscale collection mode the confocal microendoscope operates at 30 frames-per-second with 3μm lateral
resolution and 25μm axial resolution. The multi-spectral collection mode operates at 0.5 frames-per-second when
acquiring 32 spectral channels with an average minimum resolvable wavelength difference of 12nm. The system will be
used, in grayscale mode, to image ovaries during a small scale clinical trial on women undergoing oophorectomy.
Recent grayscale and multi-spectral imaging results from ex-vivo human tissues are presented.
We present a laparoscope for fluorescence confocal microendoscopy specifically designed for microscopic imaging during diagnostic laparoscopic surgery. The catheter consists of a disposable rigid distal tip which houses a flexible microendoscope and dye channel. The laparoscopic tip is a small disposable polycarbonate sheath
containing two inner lumens with a glass window on the distal end. The sheath outer diameter suitable for use in a 5mm trocar. The smaller inner lumen provides a channel for delivering fluorescent contrast agents to the tissue through a 200um hole in the glass window. On the proximal end, the smaller lumen is coupled to a computer controlled fluid delivery system that controls the amount of contrast agent dispensed onto the tissue down to a fraction of a micro liter. The main lumen houses the microendoscope. The microendoscope incorporates a computer-controlled focus mechanism that can quickly and accurately focus while correcting for
hysteresis. This fluorescence confocal micro-laparoscope will be tested in a small-scale clinical trial on women undergoing oophorectomy in the near future.
A multi-spectral confocal microendoscope (MCME) for in-vivo imaging has been developed. The MCME employs a flexible fiber-optic catheter coupled to a slit-scan confocal microscope with an imaging spectrometer. The catheter consists of a fiber-optic imaging bundle linked to a miniature objective and focus assembly. The focus mechanism allows for imaging to a maximum tissue depth of 200 microns. The 3mm diameter catheter may be used on its own or routed though the instrument channel of a commercial endoscope. The confocal nature of the system provides optical sectioning with 3 micron lateral resolution and 30 micron axial resolution. The system incorporates two laser sources and is therefore capable of simultaneous acquisition of spectra from multiple dyes using dual excitation. The prism based multi-spectral detection assembly is typically configured to collect 30 spectral samples over the visible range. The spectral sampling rate varies from 4nm/pixel at 490nm to 8nm/pixel at 660nm and the minimum resolvable wavelength difference varies from 8nm to 16nm over the same spectral range. Each of these characteristics are primarily dictated by the dispersion characteristics of the prism. The MCME is designed to examine cellular structures during optical biopsy and to exploit the diagnostic information contained within the spectral domain. The primary applications for the system include diagnosis of disease in the gastro-intestinal tract and female reproductive system. In-vitro, and ex-vivo multi-spectral results are presented.