Endomicroscopy Research

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I have a fully-funded PhD position available to work with me in the field of endoscopic microscopy (biomedical optics) at the University of Kent, starting in September 2017.

My current research is primarily focused on endomicroscopy, a technique that allows us to image human tissue at a cellular level in real time. It relies on miniaturised microscope probes, built using fibre optic technology, which are small and flexible enough to be passed along the instrument channel of an endoscope. Following the application of staining agents to the issue, the probe can be used to display a live microscope video-feed to the operator.

fbe_probe2Endomicroscopy offers an approach which is radically different from the normal way of imaging human tissue. In conventional histology, small amounts of tissue are extracted from the patient during a biopsy procedure and sent to a laboratory to be viewed under a bench-top microscope. With endomicroscopy, instead of waiting hours or days for a report from the histopathology lab, clinicians can see the results immediately. This is known as taking an 'optical biopsy'.

Endomicroscopy has developed significantly over the past ten years (see Jabbour et. al [2] for a review) and has recently been commercialised by Mauna Kea Technologies and Optiscan. Unfortunately, the sensitivity and specificity of optical biopsy cannot always compete with standard histology [3], and the technique has yet to enter routine use in most hospitals [2]. While optical biopsy will probably never completely replace physical biopsy, it does have the potential to allow better targeting of conventional histology [1].  Taking smaller numbers of biopsies means less risk for the patient and also potentially lowers the costs for histology. There is also potential to guide surgical procedures in real time, particularly for the resection of tumours.

REBOT

From June 2016 I have been researcher co-investigator on an EPSRC funded project called 'REBOT: Robotic endobronchial optical tomography'. This collaboration between the University of Kent and Imperial College London is developing a robotic system for high-resolution imaging of the peripheral reaches of the lung, beyond the reach of conventional bronchoscopes. I am working to integrate some of the endomicroscopy-related technology we have developed, as well as investigating new imaging systems and co-ordinating work between the robotic engineers and computer scientists at the Hamlyn Centre and the optical engineers and physicists at the University of Kent's Applied Optics Group.

SMART ENDOMICROSCOPY

From 2011-2016 I worked as part of a team on an EPSRC funded project, led by Prof Guang-Zhong Yang, which aimed to develop technological improvements in endomicroscopy to aid more widespread clinical adoption. In particular, we worked on methods for improving the image resolution and field of view, enabling us to characterise larger areas of tissue. Robotic technologies are a strong candidate, as they allow us to obtain a degree of dexterity not possible with manual control. Our perspective [4] in Computerized Medical Imaging and Graphics discusses some of the challenges and potential solutions in more detail. We are now using a follow-up grant, SMART Endomicroscopy Translational Alliance, to look at how some of the technology we developed can be translated to the clinic, in partnership with Smallfry and the Gates Foundation.

HIGH-SPEED ENDOMICROSCOPY

We have developed high frame rate endomicroscopes (120 fps) which offer depth sectioning using the line scanning technique [5, 6]. The advantage of a high frame rate is that we are better able to assemble mosaics (i.e. stitch together images) even when the endomicroscope probe is moved rapidly across the tissue. We have also shown that we can enhance the optical sectioning to near that of a point-scanning confocal endomicroscope using a two-step technique [6].

mosaic_linescan

Mosaic of ex vivo porcine colon tissue acquired with high frame rate endomicroscope.

WHITE LIGHT ENDOMICROSCOPY

Endomicroscopes normally operate in fluorescence mode, but there are some advantages to working with white light and coloured stains. We have shown two ways in which colour endomicroscopy can be achieved with fibre bundles, overcoming problems due to back-reflections of the illumination light from the fibre tips. In the first [7], we used a side-illumination scheme, relying on light scattering from adjacent tissue areas to illuminate the tissue of interest. In the second [8], we illuminate the tissue through the cladding of the fibre bundle.

whitelightcolon

Colour reflectance endomicroscopy image of porcine colon ex vivo, stained with toluidine blue.

ROBOTIC ENDOMICROSCOPY

I have been working with current and former colleagues, particularly Siyang ZuoPetros Giataganas, Lin Zhang, and Chris Payne to integrate robotics and other smart technology [9] with endomicroscopy imaging probes. We are particularly focused on applications in breast conserving surgery [10,11,12] and transanal endoscopic microsurgery.

ENDOMICROSCOPY FOR BREAST SURGERY

Along with Khushi Vyas, Daniel Leff, Tou Pin Chang and others, I have been exploring potential applications of endomicoscopy for real-time assessment of tumour margins during breast surgery. A recent study led by Khushi Vyas [13] and an older study led by Tou Pin Chang [14] demonstrate the potential very clearly.

REFERENCES

[1] Wang T.D., van Dam, J., "Optical Biopsy: A New Frontier in Endoscopic Detection and Diagnosis", Clin Gastroenterol Hepatol. 2(9): 744-753 (2004);

[2] Jabbour, J. M., Saldua, M., Bixler, J. N., Maitland, K. C., "Confocal Endomicroscopy: Instrumentation and Medical Applications", Ann. Biomed. Eng. (2011);

[3] Bajbouj, M.,  Vieth, M., Rasch, T.,  Miehlke, S., Becker, V., Anders, M., Pohl, H., Madisch, A., Schuster, T., Schmid, R.M.,Meining, A., "Probe-based confocal laser endomicroscopy compared with standard four-quadrant biopsy for evaluation of neoplasia in Barrett's esophagus", Endoscopy 42(6): 435-440 (2010);

[4] M.Hughes and G-Z Yang, "Perspective: Robotics and smart instruments for translating endomicroscopy to in situ, in vivo applications", Computerised Medical Imaging and Graphics 36, 589 (2012) [Pre-print PDF].

[5] M. Hughes and G-Z. Yang, "High speed, line-scanning, fiber bundle fluorescence confocal endomicroscopy for improved mosaicking" Biomedical Optics Express 6, 1241-1252 (2015). [Open Access]

[6] M.Hughes, G-Z.Yang, “Line-scanning fiber bundle endomicroscopy with a virtual detector slit,” Biomedical Optics Express 7(6), 2257-68 (2016). [PDF]

[7]. M. Hughes, P. Giataganas, and G-Z. Yang, "Color reflectance fiber bundle endomicroscopy without back-reflections," Journal of Biomedical Optics 19(3), 030501 (2014). [PDF]

[8]. M. Hughes, T. P. Chang and G-Z. Yang, "Fiber bundle endocytoscopy," Biomedical Optics Express 4(11) 2781-94 (2013) [Open Access]

[9] P. Giataganas, M. Hughes, and G-Z.Yang, “Force adaptive robotically assisted endomicroscopy for intraoperative tumour identification,” International Journal of Computer Assisted Radiology and Surgery (2015) (Runner Up Best Paper at IPCAI 2015.) [Pre-print PDF]

[10] S. Zuo, M. Hughes, P. Giataganas, C. Senici, T. Chang and G-Z. Yang, "Development of a Large Area Scanner for Intraoperative Breast Endomicroscopy," IEEE International Conference on Robotics and Automation 2014.

[11] T. Chang, D. Leff, S. Shousha, D. Hadjiminas R. Ramakrishnan, M. Hughes, G-Z.Yang, A. Darzi, Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: Towards a real-time intraoperative imaging tool for cavity scanning”, Breast Cancer Research and Treatment 153(2), 299-310 (2015).

[12] S. Zuo, M. Hughes, C. Seneci, T.P. Chang, G-Z.Yang, “Towards Intraoperative Breast Endomicroscopy with a Novel Surface Scanning Device,” IEEE Transactions on Biomedical Engineering 62(12) 2941-52 (2015). [PDF]

[13]. K. Vyas, M. Hughes, D. Leff, G-Z. Yang, "Methylene-blue aided rapid confocal laser endomicroscopy of breast cancer," J. Biomed. Opt. 22(2), 020501 (2017) [PDF]

[14] T. Chang, D. Leff, S. Shousha, D. Hadjiminas R. Ramakrishnan, M. Hughes, G-Z.Yang, A. Darzi, Imaging breast cancer morphology using probe-based confocal laser endomicroscopy: Towards a real-time intraoperative imaging tool for cavity scanning,” Breast Cancer Research and Treatment 153(2), 299-310 (2015).