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Mar 20

"Engineering optics, from bench top to bedside"

The head of our department organised a talk yesterday by Bruce Tromberg. Bruce Tromberg is professor of Biomedical Engineering; professor (jointly) of the School of Medicine at the University of California, Irvine; and a Director of the Beckman Laser Institute. Additionally, he is also.... okay, I'm going to stop there as I've just found his CV posted on his homepage and it runs to 59 pages and I only wanted to write a 1000 word article. I think you can take it for granted that Professor Tromberg is very much at the bleeding edge of optics and is highly respected for his work in the application of optical techniques. If you'd like to know more you can visit his wikipedia page. (yes, he has a wikipedia page!)

Professor Tromberg's original talk was to be focused on "Medical Imaging in Thick Tissues Using Diffuse Optics" - a field that is one of many focuses of his group's work at UCIrvine. However, when he was discussing the current activities of our group on his way into the University, he decided that actually we would most likely enjoy a broader talk which focused on numerous applications of photonics. So about 2 hours before he was due to give the talk, he re-wrote the presentation (by combining a few others, I assume...) and made us a whole new one and a half hour presentation on "Engineering Optics - from bench top to bedside". Below are my notes on this talk.

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Professor Tromberg's first degree is in chemistry but his career has ended up moving him more towards photonics and medical applications. In addition to his many other roles, he is a professor of surgery (non-practicing) and has very close ties to active medical groups. His group is part of the Beckman Foundation and consists of around 20 faculty and ~120 researchers. The Beckman foundation is a group aimed at promoting research in chemistry and the life sciences, with a focus on developing new and innovated instruments and materials, as well as supporting young researchers - you can read more here.

Currently, a number of medical imaging technologies work on the principle of bringing the patient to the device. This can be seen for CAT scans and MRIs - both of which have a very high initial capital cost, high running costs and require skilled and often dedicated operators. The ideal model for future systems is to move from this patient-to-technology model and develop devices that can be used in a wider range of settings at the point of care (e.g. at home or in local clinics). Current working examples of photonics being used to promote this move to point-of-care include simple things such as smart phone apps that are capable of accurately recording your pulse.

NOTE: I had heard of these heart rate apps before but I had assumed they were one of many scam/hoax apps on the phone and wouldn't be any good. However, after Professor Tromberg's talk we downloaded one and tried it out and found them to be very accurate. I strongly recommend that you download one and give it a go (links to the apps we used are: iPhone or Android).

Other examples of enabling technologies derived from photonics, range from the now very common LASIK to the more recent use of optical coherence tomography to study and understand conditions of the eye.

The next phase in the exploitation of photonics is further into the field of diagnostics and using photonics systems to see beneath the surface of the disease. There are a wide range of techniques that can achieve this, ranging from nanoscopy (high resolution but short penetration) to diffuse tomogrpahy (deeper penetration at the cost of resolution).

Graph

Reproduced from Professor Tromberg's talk with permission

Non-Linear Optical Microscopy

One technique that Professor Tromberg has worked with is using Non-linear Optical Microscopy in a clinical setting. These microscopes use a number of optical effects to image a number of structures within the dermal layers - collagen has a clear second harmonic generation; cells (specifically the NADP and FAD within them) show a florence reaction; structural features tend to be strong scatterers; and finally, lipids can be imaged using a technique known as 'Coherent anti-stokes ramen spectroscopy' (CARS). Some of the most striking uses of this technology was in the imaging of suspected lesions within the skin of a patient. In the image below you can clearly see individual cells and the distinctive change in morphology in possible lesions.

Reproduced from Professor Tromberg's talk with permission

Reproduced from Professor Tromberg's talk with permission

These microscopes have now been commercialised and are used in hospitals across the US, and are finding widespread use in looking at a number of biologically relevant structures.

In Vivo Microendoscopy

Mouse cortex

Doppler OCT image of a mouse cortex. Reproduced from Professor Tromberg's talk with permission

Also within the UCIrvine group, Professor Zhongpin Chen has been at the forefront of the use of a number of in vivo optical techniques which allow for the imaging of internal lumens (e.g. airways and blood vessels). The combination of OCT and ultrasound allow for the building up of a complex 3D picture of the walls around the vessel and in the case of blood vessels, the build up of plaque. This technique is allowing doctors, for the first time, to accurately image regions ahead of stent implant surgery and subsequent monitoring of possible re-growth around the stent.

This kind of OCT imaging can also be used to create 3D maps of blood vessels using doppler OCT. This technique relies on calculating the correlation between multiple images to show the moving areas within a depth of around 5mm.

In vivo macroscopic imaging

This area of photonics imaging can be considered the domain of wide field cameras. This kind of imaging is often works by analysing reflected light from the surface of the skin over a wide area using one or more specialist illumination methods. Spatial frequency domain imaging (SFDI) is one such technique that is being used by surgeons within the Beckman Institute and uses a similar method to the Microsoft Kinect system for the xbox 360 - it projects a series of lines in the IR range on to the subject and then alters the frequency of these lines. Using the reflected data, it is then possible to build up a map of the underlying blood vessel structures to a result with low resolution (~5mm). In addition to the structure it is also possible to derive the concentration of oxygenated haemoglobin which is highly significant for a number of clinical applications.

Skin patterns

SFID imaging of blood vessels. Reproduced from Professor Tromberg's talk with permission

Despite the relatively low resolution, this system is being used by surgeons to determine the blood oxygenation of tissues during surgery. If for example, a flap of skin that is being manipulated during surgery looses too much oxygen supply, it may cause complications in future recovery. By monitoring a live image of the oxygenation of that tissue, the surgeon can see what further action needs to be taken.

NOTE: Professor Tromberg showed an excellent movie of this being used mid-operation however, it didn't transfer over correctly so I can't include it in this post.

This kind of macroscopic imaging is also being used along with fluorescent tags in cancer surgery to identify the lymph nodes within the patient. Traditionally, this was done using blue dye injected into the patient and visually tracked by the surgeon. However, this process can be error prone and deeper lymph nodes can be missed. The use of macroscopic imaging techniques can improve this by showing the surgeon the movement of the dye through a number of possibly hidden structures.

Diffuse optics

Finally, Professor Tromberg talked about the use of optical techniques to examine  biologically relevant information from a large area with diffused light sources. An excellent example of this being put in to practice is the use of NIR blood oxygen monitoring before and during surgery to improve survival rates and to identify high risk patients. This technology has now also been expanded to monitor patient reaction to common anaesthetics and provide a wealth of new insight into how they can influence patent recovery.

Diffuse optics are also proving vital in breast cancer screening for patients with dense mammary tissue that is difficult to resolve in routine screening procedures. These techniques help separate the higher risk patients and prevent either un-neccassary biopsies or missed diagnosis. Also like the monitoring of blood oxygen levels these diffuse techniques can be used to provide constant monitoring to asses the patient's state and reaction to chemotherapy medication providing new insight for the clinicians treating the tumour.

Summing up

Professor Tromberg's concluding remarks were that the work his group has undertaken would not have been possible without the links to other fields which provide insight into application requirements. Having researchers that are trained in both photonics and healthcare, has been vital to developing novel techniques to solve long standing medical problems that wouldn't otherwise be apparent to people specialising in only photonics. He again re-iterated this in answer to Dr James' question at the end of the lecture, regarding how to manage cross-discipline projects - "Ideally you need a dedicated SWAT team that can find applications for techniques you work with. A mixed team is vital is developing those technologies further".