Peter H. Tomlins

Theory, developments and applications of optical coherence tomography

In this paper, we review the developments in optical coherence tomography (OCT) for three-dimensional non-invasive imaging. A number of different OCT techniques are discussed in some detail including time-domain, frequency-domain, full-field, quantum and Doppler OCT. A theoretical treatment is given and some relevant comparisons made between various implementations. The current and potential applications of OCT are discussed, with close attention paid to biomedical imaging and its metrological issues.

Spatially deconvolved optical coherence tomography

In this paper we present spatially mapped point-spread function (PSF) measurements of an optical coherence tomography (OCT) instrument and subsequent spatial deconvolution. The OCT B-scan image plane was divided into 2400 subimages, for which PSFs were determined from OCT measurements of a specially designed phantom. Each PSF was deconvolved from its corresponding subimage of the phantom using the Lucy-Richardson algorithm. Following deconvolution, all of the subimages were reassembled to form a final deconvolved image, from which the resolution improvement was quantitatively assessed. The lateral resolution was found to improve by 3.1 microm compared to an axial resolution enhancement of 4.5 microm. The spatial uniformity of both axial and lateral resolution was also observed to increase following deconvolution, demonstrating the advantage of deconvolving local PSFs from their associated subimages.

Scattering attenuation microscopy of oral epithelial dysplasia.

We present a new method for quantitative visualization of premalignant oral epithelium called scattering attenuation microscopy (SAM). Using low-coherence interferometry, SAM projects measurements of epithelial optical attenuation onto an image of the tissue surface as a color map. The measured attenuation is dominated by optical scattering that provides a metric of the severity of oral epithelial dysplasia (OED). Scattering is sensitive to the changes in size and distribution of nuclear material that are characteristic of OED, a condition recognized by the occurrence of basal-cell-like features throughout the epithelial depth. SAM measures the axial intensity change of light backscattered from epithelial tissue. Scattering measurements are obtained from sequential axial scans of a 3-D tissue volume and displayed as a 2-D SAM image. A novel segmentation method is used to confine scattering measurement to epithelial tissue. This is applied to oral biopsy samples obtained from 19 patients. Our results show that imaging of tissue scattering can be used to discriminate between different dysplastic severities and furthermore presents a powerful tool for identifying the most representative tissue site for biopsy.

Quantitative analysis of optical coherence tomography and histopathology images of normal and dysplastic oral mucosal tissues

Selecting the most representative site for biopsy is crucial in establishing a definitive diagnosis of oral epithelial dysplasia. The current process involves clinical examination that can be subjective and prone to sampling errors. The aim of this study was therefore to investigate the use of optical coherence tomography (OCT) for differentiation of normal and dysplastic oral epithelial samples, with a view to developing an objective and reproducible approach for biopsy site selection. Biopsy samples from patients with fibro-epithelial polyps (n = 13), mild dysplasia (n = 2), and moderate/severe dysplasia (n = 4) were scanned at 5-μm intervals using an OCT microscope and subsequently processed and stained with hematoxylin and eosin (H&E). Epithelial differentiation was measured from the rate of change (gradient) of the backscattered light intensity in the OCT signal as a function of depth. This parameter is directly related to the density of optical scattering from the cell nuclei. OCT images of normal oral epithelium showed a clear delineation of the mucosal layers observed in the matching histology. However, OCT images of oral dysplasia did not clearly identify the individual mucosal layers because of the increased density of abnormal cell nuclei, which impeded light penetration. Quantitative analysis on 2D-OCT and histology images differentiated dysplasia from normal control samples. Similar analysis on 3D-OCT datasets resulted in the reclassification of biopsy samples into the normal/mild and moderate/severe groups. Quantitative differentiation of normal and dysplastic lesions using OCT offers a non-invasive objective approach for localizing the most representative site to biopsy, particularly in oral lesions with similar clinical features.

Optical coherence refractometry

We introduce a novel approach to refractometry using a low coherence interferometer at multiple angles of incidence. We show that for plane parallel samples it is possible to measure their phase refractive index rather than the group index that is usually measured by interferometric methods. This is a significant development because it enables bulk refractive index measurement of scattering and soft samples, not relying on surface measurements that can be prone to error. Our technique is also noncontact and compatible with in situ refractive index measurements. Here, we demonstrate this new technique on a pure silica test piece and a highly scattering resin slab, comparing the results with standard critical angle refractometry.

Processing and rendering of Fourier domain optical coherence tomography images at a line rate over 524 kHz using a graphics processing unit.

In Fourier domain optical coherence tomography (FD-OCT), a large amount of interference data needs to be resampled from the wavelength domain to the wavenumber domain prior to Fourier transformation. We present an approach to optimize this data processing, using a graphics processing unit (GPU) and parallel processing algorithms. We demonstrate an increased processing and rendering rate over that previously reported by using GPU paged memory to render data in the GPU rather than copying back to the CPU. This avoids unnecessary and slow data transfer, enabling a processing and display rate of well over 524,000 A-scan∕s for a single frame. To the best of our knowledge this is the fastest processing demonstrated to date and the first time that FD-OCT processing and rendering has been demonstrated entirely on a GPU.

Dynamic monitoring of refractive index change through photoactive resins

OBJECTIVES The change in optical characteristics through the bulk of curing photopolymers is not fully understood. Photopolymerization processes are accompanied by photoinitiator absorption, density changes and volumetric shrinkage, which alter optical properties and affects curing efficiency through depth. METHODS This investigation demonstrates the use of a novel low coherence interferometry technique for simultaneous measurement of optical (refractive index) and physical (shrinkage) properties throughout curing of photoactive monomers containing various concentrations of bisphenol-A-diglycidyl ether dimethacrylate and triethylene glycol dimethacrylate. RESULTS Reliability of the interferometry technique was compared with an Abbé refractometer and showed a significant linear regression relationship (p<0.001; adjusted R(2)>0.99) for both uncured and cured resins. The extent and rate of refractive index change and magnitude of shrinkage strain was dependent upon monomer formulation. SIGNIFICANCE The development of this interferometry technique provides a powerful non-invasive tool that will be useful for improving light transmission through photoactive resins and filled resin composites by precise control of optical properties through material bulk.

Femtosecond laser micro-inscription of optical coherence tomography resolution test artifacts.

Optical coherence tomography (OCT) systems are becoming more commonly used in biomedical imaging and, to enable continued uptake, a reliable method of characterizing their performance and validating their operation is required. This paper outlines the use of femtosecond laser subsurface micro-inscription techniques to fabricate an OCT test artifact for validating the resolution performance of a commercial OCT system. The key advantage of this approach is that by utilizing the nonlinear absorption a three dimensional grid of highly localized point and line defects can be written in clear fused silica substrates.

Time-resolved simultaneous measurement of group index and physical thickness during photopolymerization of resin-based dental composite

Light-activated resin-based dental composites are increasingly replacing dental amalgam. However, these materials are limited by inefficient setting reactions as a function of depth that constrain the maximum extent of cure. Insufficient curing can contribute to an overall reduction in biocompatibility of the material. We demonstrate dynamic refractive index measurements of a commercial dental composite throughout cure using spectral domain low coherence interferometry. Our results show a linear relationship between the change in refractive index and polymerization-induced reduction in physical thickness during light-activated curing. This relationship between the optical and physical density demonstrates the potential of this technique as a unique noninvasive tool for measurement of the conversion degree of curing dental composite materials.

Digital phase stabilization to improve detection sensitivity for optical coherence tomography

Optical coherence tomography has become an important tool for medical imaging and increasingly for quantitative metrological applications. As a consequence detection sensitivity is highly valued. In this paper, we introduce a novel post-processing technique for digitally stabilizing and spectrally averaging optical coherence tomography datasets in order to enhance detection sensitivity. We demonstrate sensitivity gains of 18 dB when the algorithm is applied to data from a high-speed Fourier domain system.