Keep healing real with OCT

If you want a high resolution, real-time instrument offering a non-contact, non-invasive technique with clinical applications - such as the dynamics of wound healing – you need OCT says Jon Holmes

“In clinical applications, OCT could function as an "optical biopsy" to image tissue microstructure in situ and in real-time.”

OPTICAL COHERENCE TOMOGRAPHY - or OCT - is a non-contact, non-invasive, real-time imaging technique. Commercial OCT systems are widely used in ophthalmology to map at the pixel level the anatomic layers within the retina and create cross-sectional images of retinal pathology. These are achieved with higher resolution than any other non-invasive imaging technique. The list of clinical applications continues to expand but OCT enables micron-scale cross sections to be captured of many optical scattering media, of which biological tissue is but one.

The technique was conceived independently by Tanno and Chiba of Yamagata University in 1990, and by Huang and Fujimoto at MIT in 1991(1,2). The approach is analogous to ultrasound or Magnetic Resonance Imaging (MRI), except that imaging is performed by measuring the echo time delay and intensity of reflected laser light rather than sound or radio waves. Laser light is projected into tissue and, although most is 'scattered' and undetectable on its way back to the surface, a proportion of the light is not scattered (coherent - solid arrow) and is detected by an optical interferometer, which discards the scattered light (dotted arrows) and uses depth and intensity information to generate an image (Figure 1).
Although imaging depths are typically around 2mm, which is shallow compared with MRI or ultrasound, OCT can provide much higher image resolution on the micron scale. An optical focus provides lateral resolution and 2-D and 3-D cross-sectional OCT images of tissue are constructed by scanning the optical beam and performing axial measurements of light echoes at different transverse positions.  However, until recently, it has not been possible to achieve high lateral resolution throughout the desired imaging depth. While axial resolution is determined by light source properties, the lateral resolution is a function of the numerical aperture (N.A.), which is a function of the desired depth of focus.

To overcome this fundamental limitation of traditional, single-beam FD-OCT

Figure 1: Light scattering paths in tissue

systems, we have developed a solution that simultaneously scans with multiple beams focused at slightly different depths and compiles an image mosaic from the resulting multiple FD-OCT interferograms. For example, a four beam system focused over 1.0mm, with each sub-beam focused over 0.25mm, produces double the resolution possible from a single beam. Each sub-beam has a theoretical FWHM diameter of just 10.3μm.

Multi-Beam OCT technology has been implemented in the EX1301 OCT Microscope, suitable for ex-vivo applications, and in the new ‘VivoSight’ hand-held probe, designed for clinical applications and recently awarded a CE mark for clinical use.

To demonstrate the potential of Multi-Beam OCT for monitoring the progression of wound healing, an OCT image of  skin on the back of  the author’s hand  was taken using a Michelson Diagnostics’ EX1301 OCT Microscope. This image is shown in Figures 2 and 3. The progress of the wound healing process is visible, including scab formation and gradual expulsion of the scab as the epidermis re-grows underneath.

OCT is already proving useful in ophthalmology and other clinical fields. Image

Figure 2: OCT Image of healthy skin immediately prior to infliction of small wounds. Image size 5mm X 2mm approx

information gathered in can be quantitatively analysed to measure specific features, such as retinal thickness or nerve fibre layer thickness, which are indicators of diabetic retinopathy or glaucoma. In this and other clinical applications, OCT could function as an "optical biopsy" to image tissue microstructure in situ and in real-time. It may be particularly useful where excisional biopsy would be hazardous or impossible, such as imaging the retina, coronary arteries or nervous tissues, and is being developed to guide excisional biopsy in a bid to reduce false negatives and improve imaging sensitivity. Since OCT can see beneath the surface of tissue, it could also be used to guide surgical interventional procedures. OCT also has the advantage that it can perform repeated imaging over a period of time and therefore potentially monitor the progression of disease or response to therapy.

We have shown that Multi-Beam OCT may also be used to allow the non-

Figure 3: A series of five images taken over four days showing formation of scabs and re-growth of epidermis. Image size 5mm X 2mm approx

invasive, non-contact tracking of wound healing in real-time and at high-resolution, and believe that it could be a powerful monitoring tool.  For instance, in burns units and other clinical situations involving skin grafts. Other clinical uses may be in monitoring the invasion of tissue scaffolds in vivo (Figure 4) and in histopathology, which is signally lacking in its ability to predict or observe progression, providing only a snapshot of a part of the lesion and destroying the tissue and the pathology in the process. For instance, there is a pressing need for a tool that allows accurate monitoring of oral tissue lesions. OCT is non-invasive, non-destructive, can be used to systematically scan the whole lesion, and may enable visualisation of tissue architecture in terms of depth and size. It is expected to be ideal for monitoring change in patients. Multi-Beam OCT may allow visualisation of blood vessels and capillaries in high resolution (Figure 5), revealing a wealth of clinical details and making it an ideal non-invasive tool for researchers in many disciplines.

Here we have shown that multi-beam OCT could be used for imaging applications in regenerative medicine, non-invasively, in real-time and at high-resolution. An instrument with clinical approvals will be available mid-2009.
For this and other clinical applications, the benefits offered by OCT are clear:

• Live sub-surface images at near microscopic resolution
• Instant, direct imaging of sub-surface microstructure
• No preparation of the sample required
• Eye-safe near infrared light used - no sample damage likely
• No ionising radiation - for use in office, clinic or lab

Figure 4: Tissue scaffold (image courtesy of University of Edinburgh)	Figure 5: Multi-Beam OCT image of a section of skin, approx 5mm by 1.4mm with a resolution <10μm