2694 IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING, VOL. 58, NO. 9, SEPTEMBER 2011 A Hand-held Instrument to Maintain Steady Tissue Contact during Probe-Based Confocal Laser Endomicroscopy Win Tun Latt*, Richard C. Newton, Marco Visentini-Scarzanella, Christopher J. Payne, David P. Noonan, Jianzhong Shang, and Guang-Zhong Yang, Fellow, IEEE Abstract—Probe-based confocal laser endomicroscopy (pCLE) provides high-resolution in vivo imaging for intraoperative tissue characterization. Maintaining a desired contact force between tar- get tissue and the pCLE probe is important for image consistency, allowing large area surveillance to be performed. A hand-held in- strument that can provide a predetermined contact force to obtain consistent images has been developed. The main components of the instrument include a linear voice coil actuator, a donut load-cell, and a pCLE probe. In this paper, detailed mechanical design of the instrument is presented and system level modeling of closed- loop force control of the actuator is provided. The performance of the instrument has been evaluated in bench tests as well as in hand-held experiments. Results demonstrate that the instrument ensures a consistent predetermined contact force between pCLE probe tip and tissue. Furthermore, it compensates for both simu- lated physiological movement of the tissue and involuntary move- ments of the operator’s hand. Using pCLE video feature tracking of large colonic crypts within the mucosal surface, the steadiness of the tissue images obtained using the instrument force control is demonstrated by confirming minimal crypt translation. Index Terms—Confocal endomicroscopy, force adaptive control, hand-held imaging probe, pCLE, tissue characterization. I. INTRODUCTION W ITH recent advances in biophotonics, there is an in- creasing demand on the development of smart surgical instruments integrated with miniaturized imaging probes for in situ, in vivo imaging. Thus far, several “optical biopsy” methods, such as optical coherence tomography [1], [2] and confocal en- domicroscopy [3], [4] are used to provide high-resolution in vivo tissue images which have the potential to enhance diagnosis, Manuscript received April 12, 2011; revised June 7, 2011; accepted June 18, 2011. Date of publication July 14, 2011; date of current version August 19, 2011. Asterisk indicates corresponding author. *W. T. Latt is with the Hamlyn Centre for Robotic Surgery, Imperial College London, London SW7 2AZ, U.K. (e-mail: w.tun-latt@imperial.ac.uk). R. C. Newton is with the Department of Surgery and Cancer, Imperial College London, London SW7 2AZ, U.K. (e-mail: r.newton@imperial.ac.uk). M. Visentini-Scarzanella, C. J. Payne, D. P. Noonan, J. Shang, and G.- Z. Yang are with the Hamlyn Centre for Robotic Surgery, Imperial College London, London SW7 2AZ, U.K. (e-mail: marco.visentini-scarzanella02@ imperial.ac.uk; christopher.payne04@imperial.ac.uk; dnoonan@imperial.ac. uk; j.shang@imperial.ac.uk; g.z.yang@imperial.ac.uk). Color versions of one or more of the figures in this paper are available online at http://ieeexplore.ieee.org. Digital Object Identifier 10.1109/TBME.2011.2162064 and provide valuable real-time information during endoscopic procedures or open surgery. Thin (<2.5 mm diameter) probe- based confocal endomicroscopy (pCLE) probes can be passed down endoscopes and may facilitate diagnosis within the gas- trointestinal tract lumen [5], lung [6], bladder [7], and peritoneal cavity [8]. Potential benefits of integrating pCLE into diagnostic and interventional procedures include 1) improving the targeting and yield of traditional pinch biopsies, 2) supplying dynamic in vivo images that are not impaired by crush or fixation artefact and provide information about blood perfusion, 3) obviating the need for pinch biopsy of benign lesions such as hyperplastic polyps in the bowel, 4) enabling larger areas of tissue to be “optically biopsied” than would ever be possible with “pinch biopsy,” 5) by facilitating intraprocedure tissue diagnosis, patients can avoid laboratory delays and repeated procedures, and 6) with the con- tinuing uptake of more conservative surgery such as endoscopic mucosal resection for early-stage gastric cancer, pCLE may be able to accurately delineate the tumour margins during the resection. Alternative approaches to obtain in vivo confocal en- domicroscopic images include pCLE using a flexible endoscopic snake robot [9], or to use larger diameter hand-held rigid probes during open abdominal surgery [10], examination of the uterine cervix [11], mini-laparoscopy of the liver [12], or during rigid bronchoscopy [13]. However, regardless of how the technology is employed, probe manipulation is paramount to obtaining con- sistency with such highly magnified images. The probe requires constant perpendicular contact with the tissue, and it must re- main steady despite movement of the operator, bowel mobility, peristalsis and cardiorespiratory movement. Small variations in contact force demonstrably alter the image, and the infor- mation acquired. Indeed, colonic crypt morphology is affected by pCLE probe pressure [14], a “compression effect” is seen in pCLE of the peripheral lung [15], and pressure effects have been shown in probe-based spectroscopic methods [16]. To increase the small field of view of pCLE, slow and steady probe transla- tion over the tissue enables adjacent images to be “stitched” to- gether, creating larger field of view “mosaics” of a few millime- tres [17]: this presents further opportunity for contact pressure fluctuations. Several force control systems or devices have been developed for various medical applications. Dombre et al. [18] developed a robotic system for maintaining a desired contact force dur- ing the harvesting of skin grafts. Force control for grasping soft tissue is presented in [19]. Design and development of a hand-held instrument for maintaining a contact force in beating 0018-9294/$26.00 © 2011 IEEE