The Noninvasive Eye-Opener

The term “optical biopsy” has entered into common use among researchers in biomedical optics. It’s defined as an optical measurement, often a type of spectroscopy, used to perform a noninvasive tissue diagnosis in vivo and in real-time. It’s hoped that these techniques will reduce the need for surgical removal of biopsy tissue samples; instead, a spectral analysis of the tissue in vivo is recorded by an imaging system, or with an optical probe placed on or near the surface of the tissue. Then, based on the optical measurements, a diagnosis can be made.

Optical biopsy has some specific advantages over traditional methods. Consider, for example, the clinical diagnosis of melanoma and other skin cancers, which is still performed primarily by sight. Since even the most sophisticated eye is fallible, there’s a chance that skin cancer might be visually diagnosed as benign, or that a benign mole might be unnecessarily biopsied in an invasive procedure. As reported in the journal Dermatologic Surgery, nearly 80 percent of all skin biopsies performed result in benign diagnoses (1) – so patients undergoing traditional biopsy must endure not only the chance of being misdiagnosed with cancer, but also the pain and potential subsequent scarring if their doctor deems an invasive biopsy necessary.

Nervous patients, especially, face difficulties with traditional biopsy methods. Many skin lesions occur on cosmetically sensitive parts of the body, such as the face, so apprehensive patients might choose not to undergo the procedure at all. If they do, they might experience anxiety while waiting for the biopsy results, which can take up to two weeks with traditional biopsies. Using optical biopsy techniques avoids issues like these; the procedure is not invasive and the images obtained can be diagnosed at the point of care, eliminating long wait times.

A bumpy road to acceptance

Despite the apparent value of this new approach, optical biopsy has faced some hurdles on the road to general acceptance. First, the development of the associated imaging technology has taken time. For example, confocal microscopy, a laser technology, has the ability to produce high resolution images of living tissue at various depths. It works by concentrating on one focal plane at a time and reducing the out-of-focus light from above and below that plane. A computer then reconstructs the images, which are taken point-by-point rather than projected through an eyepiece.

The principle for this kind of microscopy was developed in 1953, but it didn’t become a standard technique until the late 1980s, when the high quality lasers needed to make the technology viable were developed.

Doctors interested in optical biopsy face the task of familiarizing themselves with the new technology before they can use it properly. In general, though, technicians are capable of obtaining the actual images – whether they result from an endoscopic procedure or a spectral analysis of the skin – using established protocols. It’s the interpretation of those images that requires specialized training.

How will it affect pathologists?

If optical biopsy eventually sees widespread adoption as a standard technique, it may not be utterly transformative, but it is likely to impact the pathology community in several ways. It might, for instance, attract a new cohort of patients who are attracted by the advantages it brings: no scarring and no long wait times for diagnosis, along with a reduction in psychological trauma. This has the potential to improve rates of diagnosis. But some pathologists worry that, even with the influx of new patients, optical biopsy might reduce the need for pathology services. Far from taking away from the roles of qualified pathologists, their expertise will be as necessary as ever to interpret the optical biopsy images collected by technicians – but with increased convenience. The pathologist doesn’t need to be in the room when the procedure is performed, nor even at the same facility; the digital images can be analyzed from anywhere in the world.

The steps involved in obtaining optical biopsy images will vary according to the organ of interest. If an endoscopic procedure is needed, a very small confocal laser microscope can be used. The microscope sits at the end of a long, thin, flexible tube that can be threaded through a traditional endoscope to enter the body. It detects fluorescent light triggered by a laser; a filter removes the laser light, allowing the fluorescent light to pass through a small aperture. The light then hits a photodetector that converts the image to electronic signals, which are then displayed as images on a computer screen for the pathologist to examine.

Optical biopsy of the skin works a little differently. While conventional microscopes work by illuminating thin tissue layers from below (transmitted light), high resolution confocal microscopes designed for dermatology use incident light, which means that the skin is illuminated from above, in the horizontal plane, with a focused laser. The light is reflected at interfaces where the refractive index changes, typically at highly reflective skin structures like keratin, melanin and collagen. The reflected light is directed through a pinhole onto a detector, so that only signals from a defined horizontal plane are used for high resolution imaging. This technique limits penetration depth, but usually provides physicians with ample information to determine whether a traditional biopsy is required or whether the lesion can simply be monitored. The entire procedure takes less than 10 minutes and collects all the images needed to make an accurate, reliable diagnosis at the point of care.

The evidence

Over the past two decades, a slew of studies have reported on the efficacy of optical biopsy as a technique in tandem with various imaging technologies, involving both endoscopic procedures and skin imaging (2–4). A 2013 overview by Alfano and Pu (5) concluded, “Optical biopsy with lasers and LEDs, as an emerging technology in biomedical optical imaging, holds a promising future armamentarium for clinical diagnosis and other important medical applications.” In the same year, the Association of the Scientific Medical Societies in Germany published a guideline on behalf of the German Dermatological Society stating, “Confocal laser scanning microscopy [a key imaging technique used in tandem with optical biopsy] is suitable for dermatological, noninvasive diagnostic of near-surface skin changes. In the area of skin tumors, it is especially of interest to assess melanocytic lesions with respect to their benign or malign character in order to enable the early detection of melanoma and avoid unnecessary excisions” (6). A recent update to the Guideline on Basal Cell Carcinoma published by the European Dermatology Forum agrees, identifying confocal microscopy as an emerging technique in digital imaging diagnostics and reporting that it “has shown high diagnostic accuracy for the diagnosis of basal cell carcinoma” (7).

Skin cancer isn’t the only application for optical biopsy, though. So far, human tissues including prostate, breast, lung, colon and gastrointestinal have been studied – but applications where optical biopsy could be especially powerful, such as where conventional excisional biopsy is hazardous or impossible, should be emphasized. A good example is in ophthalmology, where traditional biopsy of the retina is impossible, but optical biopsy (in tandem with optical coherence tomography) can provide high-resolution images of pathology that can’t be obtained any other way. Hopefully, this new noninvasive technique will one day allow pathologists access to tissues – like those in the eye – that we currently have no way of examining safely. In the meantime, optical biopsy is an exciting, rapidly developing technique with the potential to improve the diagnostic accuracy for a wide variety of medical specialties.