Optical Coherence Tomography (OCT): A Noble Diagnostic Biomedical Imaging Tool & my Tryst with it.

 

A fortnight ago, I had written about my right eye ailment and how it got aggravated due to a delayed diagnosis, which later turned out to be what is medically termed as ‘Anterior Uveitis’. Fortunately, the doctors could accurately diagnose my eye condition courtesy a biomedical engineering diagnostic tool – the Optical Coherence Tomography (OCT). Modern advancements in OCT and Raman spectroscopy hold great promise in providing new insights into the retina, which can serve ophthalmologists in saving many vision losses for their patients.

 

Uveitis is a serious eye condition characterized by inflammation of the uvea - middle layer of the eye, iris, ciliary body, and choroid. If left untreated, Uveitis can lead to disastrous consequences, a glimpse of which I had begun to experience with blurred vision and other complications. Uveitis can be classified based on the part of the uvea that is affected and, in my case, it was the Anterior uveitis (iritis): Inflammation of the front part of the uvea, including the iris and ciliary body. The technology that helped my Doctors - Dr. Jaydeep Walinjkar, Dr. Hitesh R Sharma, Dr Smit and my good friend Dr Natarajan - at the Aditya Jyot Hospital diagnose my symptoms - red eye, pain, light sensitivity, blurred vision - as Anterior Uveitis, was this noble biomedical diagnostic tool - OCT. I have accordingly been advised a proper regime of treatment for the Uveitis, which I am undergoing and hope to recover completely.

 

Now that I have been making the rounds to the Aditya Jyot hospital and my Doctor,  Dr Hitesh Sharma, and so also my good friend Doctor Natarajan - the man who founded the Aditya Jyot Hospital - have been very kind to discuss about my medical condition with me in some simple scientific terms, including showing me on screen OCT images and explaining how they are seen and interpreted, I am assured that by the time the six week Uveitis treatment regime - with the corticosteroids - are done with, my eye can come back to near normalcy - fingers crossed, they murmur. Having spent most of my professional career in science museums, I have learnt the skill of communicating complex science subjects in an easier to understand way with the public by interacting and learning the subject from experts. The challenge that I was facing with my eye provided me an opportunity on a platter to know more about Uveitis and how science and technology has helped its diagnosis. Therefore, I decided to use this opportunity to try and create an awareness about Uveitis and how early diagnosis can save patients from a possibility of permanent loss of vision and how technologies like the OCT help in early detection of such eye disorders. 

 

Doctors have helped me to understand the importance of OCT in early diagnosis by showing me and explaining the OCT images of my eye and how the data from these images can be interpreted for better understanding of the retina. OCT and such other medical diagnostic tools have resulted from harvesting the knowledge of science of nature that serves as an underpinning for development of any technology, including the medical tools that serve human society.

 

Just a couple of days ago the Times of India reported of a very high prevalence of conjunctivitis in Mumbai. In fact, I too was under the impression that I was affected with it. But then, it turned out to be something completely different and my experience has motivated me to appeal to all my friends and family that if you or any of your near and dear one’s experience symptoms such as eye redness, pain, light sensitivity, blurred vision etc. don’t neglect it as a conjunctivitis or some un harmful infection, it could be Uveitis or something else and therefore you must not delay in seeking professional medical advice as early as possible.

 Beginning in the late 1950s, but accelerating at an ever-faster pace thereafter, leading into the twenty first century, science and technology has dramatically transformed the landscape of modern medicine. The importance of S&T in modern medicine cannot be understated, more so when we  notice that before the World War a typical physician had a modest armamentarium as his toolkit in his arsenal, which included a thermometer, stethoscope, sphygmomanometer, and an occasional access to x-ray machines and electrocardiograph. These tools supplemented a limited cabinet of pharmaceuticals including sulfa drugs and negligible quantity of penicillin, which the Doctors had access to in the 1940s. 

 

There has been  a paradigm shift in the advancement of medical diagnostics, thereafter. After the World War, biological medical diagnostics research has witnessed unprecedented development with the efforts of many scientists and engineers who have helped in creating a new armamentarium of biophysics instruments- Electron Microscopes, Ultracentrifuges, Mass Spectrometers and new agents such as radioactive isotopes. A revolution in microelectronics and semiconductors initiated during the War together with the development of high computing devices, that can crunch elephantine data, have led the way to new fields of biomedical imaging such as Ultrasound, Computerized Tomography (CT), Positron Emission Tomography (PET) scanners,  Nuclear Magnetic Resonance Imaging, Magnetic Resonance Imaging (MRI) and the instrument which helped in diagnosing my eye problem,  ‘Optical Coherence Tomography (OCT). This essay will however, be confined to OCT.

 

The importance of OCT as a marvel engineering technology for benefitting medical professional can be seen from the fact that the National Academy of Engineering (NAE), a premier American institution that provides engineering leadership to the nation for advancing the welfare and prosperity of the people has awarded a highly prestigious Fritz J. and Dolores H. Russ Prize (2017) for Biomedical Engineering to a group of scientists and engineers  - James G. Fujimoto, Adolf F. Fercher, Christoph K. Hitzenberger, David Huang, and Eric A. Swanson - for their contributions to the invention of the Optical Coherence Tomography (OCT). This $500,000 biennial prize - considered as prestigious as the Nobel Prize in the field of Biomedical engineering - recognises a bioengineering achievement that significantly improves human condition. The citation for the prize reads; “leveraging creative engineering to invent imaging technology essential for preventing blindness and treating vascular and other diseases." The recipients of this Prize “personify how engineering transforms the health and happiness of people across the globe," said NAE President C. D. Mote, Jr, while making this announcement. The creators of OCT  have dramatically improved the quality of life for people with diminished eyesight.

 

As the name suggests the OCT works on the principle of optics - interferometry, where a beam of light is split into two arms - a reference arm and a sample arm. In the sample arm, the light is directed towards the tissue being examined. Some of this light is reflected back, while some is scattered or absorbed by the tissue. The light that is reflected back from different depths within the tissue is then combined with the reference light in the interferometer. By comparing the time delay of the reflected light with the reference light, OCT creates a depth profile of the tissue being examined. This information is used to construct a detailed cross-sectional image of the internal structures, allowing doctors to visualize and diagnose various medical conditions non-invasively. OCT is majorly used in ophthalmology for retinal imaging and in other medical fields like cardiology and dermatology for examining various tissues and organs.

 

OCT has now grown to become one of the most widely used technologies for imaging the human eye and is an essential tool for the treatment of blinding diseases such as macular degeneration, glaucoma, and diabetic retinopathy. It has helped doctors in diagnosing millions of patients with eye disease at early treatable stages, before irreversible loss of vision can occur. Infrared light is used in OCT because of its relatively long wavelength, which allows it to penetrate the scattering medium. The concept of OCT was first introduced in the 1960s, but significant progress was made in the 1980s and 1990s when several researchers independently developed different OCT systems. 

 

The first two-dimensional picture of the fundus - inside, back surface of the eye made up of retina, macula, optic disc, fovea and blood vessels - of a human eye in vivo ( Latin word for ‘within the living’ ) was created by Adolf Friedrich Fercher, using white light interferometry. Fercher’s visionary ideas laid the basis for the development of OCT and the first in vitro OCT images were published by German and United States researchers in 1991. Fercher began his works in this field in late 1960s, while working for a private company. Post his graduation in physics, in 1968, Fercher had started working at Carl Zeiss, Germany, on optical testing, computer holography and holographic interferometry. In 1975, he became a professor at the University of Essen, Germany. Thereafter, he served as professor of medical physics and chair of the Department of Medical Physics, at the Medical School of the University of Vienna.  Fercher published his first paper on the biomedical applications of optics while he was still working for Carl Zeiss, by  calculating light scattering in a simplified model cell. He showed that the scattered signal oscillates as a function of scattering angle and that the oscillation length is related to particle diameter. It was during his time at the University of Vienna that Fercher and his colleagues worked on low partial coherence and white light interferometry for in vivo imaging of biological tissue. Their focus was on the human eye. Although the image quality of Fercher’s 2-D interferometric depth scans of the fundus was poor compared with modern standards, the retinal thickness and the excavation of the optic disc were visible.  His works created a spark for advances in this field of biomedical optics.

 

The next major development in this field came in the United States of America. In the late 1980s, a team of researchers, led by Dr. James Fujimoto at the Massachusetts Institute of Technology (MIT) and assisted by ophthalmologists Joel Schuman, David Huang, and Carmen Puliafito, worked on this concept by using low-coherence interferometry for the measurement of corneal thickness. Unfortunately, they had limited success and therefore the group decided to test its potential in retinal imaging. This decision proved  to be providential and in 1991, leading to a widely acclaimed publication by Huang and others on the very first retinal OCT images of an ex-vivo human eye. Dr Huang named this new diagnostic technique ‘optical coherence tomography.’ Soon thereafter, the first commercially available OCT device was launched by Humphrey Instruments in 1996.

 

One of the earliest OCT systems was time-domain based OCT (TD-OCT), which used a low-coherence interferometer to measure the echo time delay of backscattered light from tissues. However, TD-OCT had limitations in terms of speed and resolution and therefore it gave way to a Spectral-Domain OCT (SD-OCT). In the early 2000s, the advent of SD-OCT dramatically improved imaging capabilities. SD-OCT employs a spectrometer to measure the entire spectrum of backscattered light simultaneously, allowing for faster acquisition rates and higher resolution. This technological leap significantly enhanced the utility of OCT in ophthalmology, enabling more detailed visualization of retinal layers and facilitating the diagnosis of various retinal pathologies. Another significant advancement in OCT technology was the development of Swept-Source OCT (SS-OCT), which uses a tunable laser as a light source. SS-OCT offers superior imaging penetration, making it especially valuable for imaging deeper structures such as the choroid. Additionally, the integration of OCT with angiography techniques has enabled the visualization of blood flow in retinal vessels, enhancing diagnostic capabilities for vascular conditions.

 

The future for the OCT would be facilitated by added functionality of biochemical analysis, which can be provided by Raman scattering. This could provide critical molecular signatures for clinicians and researchers to understand the intricacies of the problems at the cellular level. OCT microscope for ex-vivo imaging combined with Raman spectroscopy will be capable of collecting morphological and molecular information about a sample simultaneously. Raman spectroscopy - spectroscopic method based on inelastic scattering of photons - allows the intrinsic biochemical composition of a sample to be identified.  Although there are challenges in the development of this dual-mode instrument and so also certain limitations for future in-vivo retinal imaging using such a dual mode instrument, however, looking at the pace with which science and technology develops the future seems to be brighter. The combination of OCT and Raman spectroscopy could provide new insights into the retina helping shed light into the lives of darkness that many people lead due to blindness and vision loss.

 

May the benefits of science and technology continue to benefit society.

Jai. Vigyan.