On-chip Optical Coherence Tomography of Pulmonary System (OCOCToPuS)

A bronchoscopy performed to reveal a normal broncial anatomy using a flexible fiberoptic bronchoscope from the larynx to the segmental bronchi.

Principal Investigator: Prof. Iain Crowe, Photon Science Institute, Manchester University (UK)

Principal Investigator: Ashim Dhakal, BTech, MSc, PhD, Biophotonics Instrumentaiton Engg.

Co-Investigator: Dr. Gopal Lama, Pahthology Lab, PRI

Co-Investigator: Prof. Richard Hogg, Electronics and nanoscale Engg., UGlasgow (UK)

Co-Investigator: Prof. David Childs, Electronics and nanoscale Engg., UGlasgow (UK)

Co-Investigator: Prof. Richard Curry, Photon Science Institute, UManchester (UK)

Partner: Prof. Shyam Sundar Budhathoki, School of PH&CM, BPKIHS, Dharan

Partner: Prof. Roel Baets, Center of nanopotonics, UGhent/imec (Belgium)

Partner: Prof. Gary Tearney, Harvard Medical School, MGH (US)

This research project aims to develop a highly miniaturized photonics integrated chip  to perform Optical Coherence Tomography (OCT), where light sources, detectors, and optical processors are all integrated on a single chip.  The target application is to image inner part of the lungs (the terminal bronchus) using the extremely small, low-cost, point-of-care system which allows a minimally trained health officer to diagnose different stages of lung diseases, particularly the chronic obstructive pulmonary disease (COPD), using a bronchoscopy procedure that can be performed across all of the 1,559 health-posts in rural areas of Nepal. Below we outline the context and technology to be used in this project.

A miniaturized photonic system is a technological revolution in the making, where optical components are miniaturized and monolithically integrated onto a single substrate. An integrated electronic circuit, as in every electronic devices, is a well-known examples of a monolithic integration where several electronic components and functionalities are miniaturized, integrated and fabricated together on a single substrate. Integration simultaneously reduces the size, inefficiencies and cost of the integrated system. With the advent of integrated photonic devices such as laser diodes, a white light emitting diode (LED), IR sensors, low-loss optical waveguides, and CMOS cameras (such as embedded in our mobile phones), the complexity and opportunities with the integrated photonic components is remarkably growing. This has opened up several applications in telecom, and biochemical sensing and other consumables. In this project, we are exploiting these opportunities to develop a miniaturized OCT technology.

One of the respected figures in Photonics integration and our partners Prof. Roel Baets explaining about Silicon Photonics, the path we will undertake for photonics integration.

OCT is a low coherence interferometry technique to image semitransparent objects, such as biological specimens. It comprises of a light source, a fairly simple Michelson-type Interferometer and a detector. Light injected into the interferometer is split into ‘sample’ and ‘reference’ arms, normally using fibre optics. The sample arm of the interferometer is used to probe the near surface region of the specimen with the image information being encoded in the interference pattern that emerges from the delay or intensity of back-scattered light from the sample with back reflected light from a mirror that terminates the reference arm. The interference pattern for several points in the specimen surface is computationally processed to reconstruct an image of the specimen cross-section.

One of the inventors of OCT, Prof. Fujimoto explains OCT in context of its history and applications.

According to WHO data, COPD is the number-one cause of deaths in Nepal, and is accountable for more than 9.2 % of the total population mortality and hence similar number of population morbidity [1]. An estimated 23% of population, 43% of the non-communicable disease burden and 2.56% of hospitalizations in Nepal are attributed to COPD [1-3]. This condition is even more serious in our rural regions, due to exposure to smoke from biomass fuel [4]. The problem is exacerbated by low oxygen level, cold climate, stark poverty, and lack of access to basic diagnostic facilities. In this project we aim to develop a simple, low-cost and point-of-care diagnostic tool to detect early stages of COPD.

Early diagnosis and management of COPD is crucial to prevent a major loss of the lung function. Unfortunately, a large population in Nepal face severe lack of basic diagnostic facilities. A detail anatomic and pathologic status of the respiratory tract at micro level is required to confirm early COPD, necessitating a high-resolution Computer Tomography imaging, which is only available in few tertiary hospitals in large cities such as Kathmandu, Pokhara and Biratnagar. OCT can provide a high-resolution image of the inner parts of the lungs at the micrometer level, thus showing even early symptoms of COPD, such as narrowed terminal bronchus due to growth (hypertrophy and hyperplasia) of bronchial mucinous glands.

One of our partners, and one fo the key inventors and developers of the OCT technology Prof. Gary Tearney explains the prospect of invivo-microscopy using OCT in pathologic dignostics and other clinical practices.

OCT is has now been fairly well established as a diagnostic system in Ophthalmology, and used routinely to image retina of the eye. With optical fibers, it has also been used to image blood vessels to image obstructions (plaques) [5-6]. Some groups have also applied this technique for imaging higher structure of the bronchus, for example, to image cancer tissues [7-8]. However, there are two major limitations of the current OCT system for the application we are seeking. The first limitation is the sheer cost, complexity and bulkiness of the current OCT systems, which is prohibitive for the application we are seeking in context of Nepal and other developing countries. In addition to integrating light sources, detectors,coptical processors and the electronics into the same miniaturizedcchip monolithically, there are number of ways we are seeking to reduce the cost and complexity of the system. One key approach is to redesign the interferometer for near-infrared wavelengths, thereby utilizing low-cost sources, optics and detectors available for shorter wavelengths. At later stages we will also look into the possibilities to integrate the systems with android based systems. The second limitation of the current OCT technology for the application we are seeking has clinical aspect: bronchial structure is highly branched system. Hence, navigating through the branches to the affected bronchial region is a huge challenge that needs to be addressed. To address this challenge, we will utilize and adapt, if needed, the existing commercial bronchoscopy system, and identify a clinical method so that the chip can be navigated through the bronchial structure in order to acquire OCT images and detecting the pathologies related tocCOPD.

An example bronchoscope we will be adapting to use for our fiber optic OCT.

In this project, we are also working closely with our advisors and partners directly linked with community medicine and public health in B.P. Koirala Institute of Health Sciences, Manmohan Cardiothoracic, Vascular and Transplant Centre and B.P. Koirala Lions Centre for Ophthalmic Studies. In addition, with our international partners in Manchester University, Glasgow University, Harvard Medical School and University of Ghent, who are world-leaders in photonics integration, development of novel sources and detectors, and clinical application of OCT techniques for a range of diagnostic problems, we will be involved in interferometer design, translating the technology towards near-infrared, and overall system design, ensuring that the technology is suitable for application in Nepal and developing countries.

  1. WHO: Nepal profile
  2. Gautam, R., et. Al., Community-based management of COPD in Nepal. Int J Chron Obstruct Pulmon Dis, 7, pp.253-57. (2012)
  3. Bhandari, R. and Sharma, R., Epidemiology of chronic obstructive pulmonary disease: a descriptive study in the mid-western region of Nepal. Int J Chron Obstruct Pulmon Dis, 7, pp.253-7. (2012)
  4. Kurmi, O.P., et al. Reduced lung function due to biomass smoke exposure in young adults in rural Nepal. European Respiratory Journal, 41(1), pp.25-30. (2013)
  5. Tearney, GJ; et al. In vivo endoscopic optical biopsy with optical coherence tomography, Science. 276 (5321): 2037–2039. (1997)
  6. Tearney, GJ; et al, "Three-Dimensional Coronary Artery Microscopy by Intracoronary Optical Frequency Domain Imaging". JACC Cardiovascular Imaging. 1 (6): 752–761 (2008)
  7. S. Schlachter and P. MacCarthy, "Next-gen OCT for the esophagus". BioOptics World. (1 May 2013)
  8. Coxson, H.O., et al., New and current clinical imaging techniques to study chronic obstructive pulmonary disease. American journal of respiratory and critical care medicine, 180(7), pp.588-597. (2009)