2.1.1.

Optical scan unit

Miniaturization of the OSU required a redesign of the previous bench-top system. By simplifying the optical layout and integrating the multispectral imaging segment into a common collection path,³⁶ we were able to fit the whole scan system into a $50\mathrm{cm}$ by $30.5\mathrm{cm}$ housing. The housing also integrates the scan mirror power supply and control electronics, which were external in the previous system.

The components of the OSU are shown in Fig. 3 . The top of the figure shows how the system operates in the standard grayscale imaging mode. In this mode, a $488\text{-}\mathrm{nm}$ solid-state laser beam is expanded and anamorphically shaped into a line via a cylindrical lens. The laser light is then reflected into the image path by a dichroic filter, imaged to a line by a microscope objective, and scanned by the object scan mirror across the coherent fiber bundle face in the microlaparoscope’s proximal connector.

Fig. 3

Diagram of the OSU. The top portion illustrates the standard grayscale mode of operation. A $488\text{-}\mathrm{nm}$ laser is anamorphically shaped into a line and scanned onto the coherent fiber bundle in the microlaparoscope. The excited signal re-enters the system, is descanned, and is filtered through a confocal slit. The light is rescanned onto a two-dimensional 2-D CCD camera. In the spectral imaging mode (bottom inset), the image scan mirror is turned to its extreme position, redirecting the light through a dispersing prism.

Tissue fluorescence is collected back through the microlaparoscope and descanned by the object scan mirror. The dichroic filter passes the fluorescence signal, which is focused down onto a stationary confocal slit. The light exiting the slit is recollimated and rescanned using the image scan mirror. An emission filter removes residual excitation light. The beam is refocused back into a line that sweeps across the camera to build up a two-dimensional (2-D) image every thirtieth of a second.

In addition to 2-D grayscale imaging, the system can also collect multispectral data.^{27, 29, 36} This multispectral mode is activated in a fraction of a second via a software actuation button that deflects the image scan mirror to its extreme position (shown in the bottom of Fig. 3). During spectral collection, the image scan mirror is held stationary. The light passes through a prism dispersing the signal across the CCD. The CCD camera records spectral information in the direction perpendicular to the slit and one dimension of spatial data in the dimension parallel to the slit. The second spatial dimension of the image is collected over time by recording multiple frames as the object scan mirror is slowly stepped. The complete spectral data collection procedure executes in a few seconds. Once spectral collection is complete, the system reverts back to real-time grayscale operating mode.

2.1.2.

Software control system

A software package that interfaces with the data collection devices and the system controls was written using Objective C 2.0 and Cocoa with automatic garbage collection on Mac OS X. Figure 4 provides a general overview of the software and hardware interface. The software links the surgical controls on the microlaparoscope to the control systems that manage contrast agent delivery, focus, and data acquisition. Parallel processing allows the software to run smoothly while live images are acquired, processed, and encoded at 30 frames per second. A custom image processing memory pool class enables efficient resource management under automatic garbage collection.

Fig. 4

Flow diagram illustrating how the software integrates the hardware, live output, and data acquisition components of the microlaparoscope system.

Figure 5 shows the software interface. It provides a simple interface for viewing and collecting live images during the surgical procedure. The software has controls to (1) start live acquisition, (2) save the current frame, (3) record video, (4) deliver dye, (5) load dye, and (6) adjust image display. In addition to the basic controls, the system also records procedure and patient information, which is archived with each image. System information, including image dynamic range and imaging depth, are also visible. During operation, the surgeon can easily see real-time imagery on the surgical display (shown in Fig. 1) along with the instrument’s current status. Contrast agent delivery, focus, and data acquisition can be initiated by the surgeon via integrated controls on the third-generation microlaparoscope handle, described in the next section.

Fig. 5

Software control system interface. The main window provides the live view and basic controls to run the system. The right side contains previews of data acquired during the procedure along with patient data.

2.2.1.

First-generation design

The first-generation design—depicted in Fig. 6 —utilized a sterilizable semirigid $5\text{-}\mathrm{mm}$ -diam by $500\text{-}\mathrm{mm}$ -long dual-lumen polycarbonate sleeve through which a nonsterile imaging catheter was inserted.³⁰ This simple design allowed us to rapidly move to clinical testing by creating a sterile housing for our existing $3\text{-}\mathrm{mm}$ flexible imaging catheter. The polycarbonate also integrated a small secondary lumen to deliver dye locally to the field of view. The front end of the polycarbonate sleeve was sealed with a $160\text{-}\mu \mathrm{m}$ -thick glass window. A $500\text{-}\mu \mathrm{m}$ -diam secondary lumen, used to deliver contrast agent, ran parallel to the primary lumen. A $200\text{-}\mu \mathrm{m}$ -diam hole in the window was placed over the secondary lumen, allowing contrast agent delivery to the tissue.

Fig. 6

First-generation microlaparoscope. The front end of the dual-lumen polycarbonate housing is shown on the right. The existing imaging catheter is inside the primary lumen, with the miniature objective flush against the glass window sealing the face. The secondary contrast agent fluid delivery lumen exits through a laser-drilled port in the glass face. The left side of the figure depicts the rear end of the polycarbonate housing passing into a $5\text{-}\mathrm{mm}$ trocar port. The dye line and imaging catheter are connected to the rear end of the housing.

The rear end of the polycarbonate housing contained the couplings to mate the imaging catheter and the dye delivery line. In the operating room, the compression coupling of the sterilized polycarbonate housing was loosened, and the nonsterile imaging catheter was fed through the main $3.1\text{-}\mathrm{mm}$ lumen until the miniature objective was in contact with the glass window. The fitting was tightened, and then a sterile plastic cover was slid back over the portion of the imaging catheter that was in the operative field. A Luer Lock fitting coupled the fluid lumen to a $0.58\text{-}\mathrm{mm}$ medical-grade Teflon tubing that ran back to the mobile cart.

The $3\text{-}\mathrm{mm}$ flexible catheter consisted of a miniature objective lens connected to durable polyetheretherketone (PEEK) tubing. The 30,000-element fiber optic bundle ran through the lumen of the PEEK tubing. Originally, focus was accomplished by a manual micrometer at the proximal end that moved the fiber bundle relative to the PEEK housing. However, focus control was unreliable due to an inexact fit of the fiber bundle inside the PEEK tubing. This resulted in hysteresis in the proximal movement of the fiber bundle relative to the fixed lens. Various methods were studied to improve the focus system.^{29, 30, 34} Ultimately, the manual focus micrometer was replaced by a computerized stepper motor. A hysteresis correction algorithm was developed to position the distal fiber face with an accuracy better than the system’s axial resolution. Figure 7 illustrates the ability of the first-generation focus system to image the epithelial surface of tissue (mouse peritoneal wall) and then to controllably focus the underlying tissue layers in $25\text{-}\mu \mathrm{m}$ increments.

Fig. 7

Image sequence demonstrating first-generation focus control and the confocal properties of the OSU. Sequence shows the process of incrementally focusing from the epithelial layer $\left(0\mu \mathrm{m}\right)$ down to the muscle layer of mouse peritoneal wall in $25\text{-}\mu \mathrm{m}$ increments. (Circular field of view is $450\mu \mathrm{m}$ .)

Dye delivery was accomplished by loading a syringe with fluorescent contrast agent. The syringe was then inserted into a syringe pump located on the mobile cart. The syringe was connected to the secondary lumen of the polycarbonate housing through $0.58\text{-}\mathrm{mm}$ -diam medical-grade Teflon tubing. Software control of the syringe pump enabled delivery of $1\text{-}\text{to}3\text{-}\mu \mathrm{L}$ droplets of contrast agent onto the tissue surface near the field of view of the miniature objective. Figure 8 shows a photograph of the distal end of the microlaparoscope with a droplet of dye coming out through the hole in the glass window.

Fig. 8

Demonstration of contrast agent delivery in the first-generation system. Delivery time was approximately one second to deliver a $1\text{-}\mu \mathrm{L}$ volume.

The device worked well using the $1.2\text{-}\mathrm{m}$ -long imaging catheter. However, it was determined that a longer length imaging catheter was needed in the operating room. With the longer length catheter, the focus motor and the syringe pump were located far from the distal microlaparoscope tip, and focus would drift during use. Delivery of small droplets of contrast agent was unreliable. The surgeon also noted that positioning the proximal tip accurately was difficult because the polycarbonate housing was not rigid enough.

2.2.2.

Second-generation design

A second-generation device was developed to address the issues concerning device rigidity, focus drift, and reliability of contrast agent delivery across a $6\text{-}\mathrm{m}$ -long connection between the microlaparoscope and the OSU. The second design abandoned the use of the existing flexible imaging catheter. To address the reliability issues of focus and dye delivery in a $6\text{-}\mathrm{m}$ -long device, the controls for focus and dye delivery were located close to the distal tip. To address the rigidity issue, a rigid instrument was made using a stainless steel tube with an inner diameter matching the fiber bundle’s outer diameter. Figure 9 shows a diagram of the second-generation microlaparoscope.

Fig. 9

The second-generation microlaparoscope. The overall device, shown on the left, incorporated a manual focus mechanism and an integrated dye delivery system that uses a piezo valve and a pressurized syringe. The right side shows a cross-section of the depth/focus knob built into the handle.

The miniature objective attached to the distal end of the $3\text{-}\mathrm{mm}$ -diam rigid stainless steel tube. The fiber bundle ran through the $1\mathrm{mm}$ inside diameter of the rigid tube. To adjust focus, the fiber bundle moved axially relative to the fixed lens position. The tube and fiber bundle were held in place by a round handle containing a manual focus mechanism. Rotation of the handle knob resulted in precise movement of the proximal fiber face relative to the rigid tube. To deliver contrast agents, a 21-gauge hypodermic tube ran parallel to the $3\text{-}\mathrm{mm}$ rigid tube. Both tubes were sealed inside medical-grade fluorinated ethylene-propylene (FEP) heat-shrink tubing, resulting in a final $5\text{-}\mathrm{mm}$ outer diameter. At the distal tip, the hypodermic tube made a $90\text{-}\mathrm{deg}$ bend, dispensing contrast agents at the edge of the imaging field. At the back end of the handle, the hypodermic tubing passed into a computer controlled piezo valve immediately downstream from a pressurized syringe. A $6\text{-}\mathrm{m}$ -long flexible cable ran from the handle to the OSU. The cable contained the fiber bundle and piezo valve electrical wires. The proximal end of the protective housing broke out into optical and electrical connectors. A standard SMA connector coupled the fiber bundle to the OSU.

Compared to the first-generation system, the second-generation system was much easier to use because the whole microlaparoscope could be sterilized and then quickly connected to the OSU in the operating room. In contrast, the first-generation system required careful placement of the sterilized polycarbonate housing over the nonsterile imaging catheter permanently connected to the OSU. The rigid stainless steel tubing solved the rigidity issues, enabling the surgeon to precisely position the device. A press of a button at the operator console enabled rapid delivery of a small droplet of contrast agent, as shown in Fig. 10 . Focus was extremely reliable and never drifted. In fact, during typical use, the surgeon would set the focus at the epithelial surface and image multiple sites without needing to refocus.

Fig. 10

Demonstration of the ability of the second-generation microlaparoscope to deliver small volumes of contrast agent to the field of view. In this sequence of images, the operator presses the dye delivery button and the dye is delivered to the distal tip via actuation of the piezo valve. The delivered volume in this example is approximately $1\mu \mathrm{L}$ .

Although the second-generation device addressed the primary issues encountered with the first-generation instrument, there were additional improvements that were important to make a successful clinical tool. Even though the manual focus system was reliable, a computerized system was desired to enable depth scans. Second, to allow the device to be controlled more efficiently by the surgeon, the microlaparoscope needed to integrate basic controls for focus, dye delivery, and data recording into the handle. The dye delivery system also needed some refinement. In the second-generation device, to ensure repeatable delivery of small contrast agent droplets, the pressure in the syringe had to be well regulated at a relatively high $1.76\mathrm{kg}∕{\mathrm{cm}}^2$ . This pressure would sometimes cause contrast agent to squirt out of the distal tip rather than pool up in a localized droplet.

2.2.3.

Third-generation design

To implement these improvements, a third-generation device was developed. The new microlaparoscope, shown in Fig. 11, has an ergonomic handle, control buttons, a computerized focus system, and a refined contrast agent delivery system. Control of focus and dye delivery are consistent and reliable since the control systems were miniaturized and located in the handle only $35\mathrm{cm}$ from the distal end of the device. A nonpressurized dye delivery system removed the problem encountered with dye ejection.

Fig. 11

The third-generation microlaparoscope. In this view, the rigid steel fiber bundle housing is visible entering into the main handle. A spring-loaded receptacle receives a $1\text{-}{\mathrm{cm}}^3$ syringe loaded with contrast agents, which couples into the fluid line running to the distal tip. Four buttons allow the surgeon to control focus, contrast agent delivery, and data acquisition. A $6\text{-}\mathrm{m}$ -long flexible line connects the microlaparoscope back to the OSU.

Mechanically, the third-generation microlaparoscope followed the same design principles as the second-generation device. Figure 12 illustrates the mechanical aspects of the device. The fiber bundle couples to the focus motor inside the handle. A $1\text{-}{\mathrm{cm}}^3$ syringe with contrast agent is placed into a spring-loaded receiver at the front end of the handle. A second miniature motor in the handle acts as a plunger for the syringe. A spring forces the syringe to mate with a Luer Lock connection that guides the fluid down a 21-gauge hypodermic tube.

Fig. 12

Detailed cross-sectional view illustrating the focus mechanism and contrast agent delivery system in the third-generation microlaparoscope. The focus motor couples to the fiber bundle, causing axial movement of the distal end of the fiber relative to the lens. The motorized syringe plunger forces fluid in the syringe to pass through the fluid line, into the tip, and out the tiny orifice at the edge of the system’s field of view. (Diagram not to scale.)

A customized tip helps to channel the dye and minimize tissue abrasion. The new tip is a $20\text{-}\mathrm{mm}$ PEEK housing mated to the FEP outer tubing. A tiny $150\text{-}\mu \mathrm{m}$ lumen inside the PEEK couples the hypodermic fluid line routing the dye to an exit port at the edge of the system’s field of view. In the second-generation design, the hypodermic tubing was bent around the tip of the miniature objective and had the potential to abrade the tissue surface. The new smooth tip helps to protect the tissue surface and allows the fluid exit port to be placed closer to the edge of the imaging field of view.

The handle contains four ergonomically positioned controls. Two upper thumb controls on the back allow the surgeon to adjust focus and acquire a depth scan. The trigger button saves still frames with a short press and acquires video with a long press. The side button delivers a predefined amount of contrast agent to the field of view.

The electrical wires and the fiber bundle are routed through the handle into a flexible $6\text{-}\mathrm{m}$ protective cable. The rear end of the cable breaks out into an electrical connector and an SMA connector. Both connections couple to receptacles on the OSU. The electrical connection routes through the electronics of the OSU and exits as a single USB cable connecting to the computer which link the buttons and motors to the control software. The SMA connector couples the fiber bundle to the OSU.

The third-generation microlaparoscope represents a viable surgical tool. Its rigid probe enables precise positioning control. The in-handle computerized focus system enables axial focus and depth scans with accurate $1\text{-}\mu \mathrm{m}$ positioning. The contrast agent system delivers volumes with precision down to $50\mathrm{nL}$ . Last, the whole device has an ergonomic design that is comfortable for the surgeon to use and provides controls for all the tasks that the surgeon needs to perform.