D.J. Faber

Localized measurement of optical attenuation coefficients of atherosclerotic plaque constituents by quantitative optical coherence tomography

Optical coherence tomography (OCT) is a novel, high-resolution diagnostic tool that is capable of imaging the arterial wall and plaques. The differentiation between different types of atherosclerotic plaque is based on qualitative differences in gray levels and structural appearance. We hypothesize that a quantitative data analysis of the OCT signal allows measurement of light attenuation by the local tissue components, which can facilitate quantitative spatial discrimination between plaque constituents. High-resolution OCT images (at 800 nm) of human atherosclerotic arterial segments obtained at autopsy were histologically validated. Using a new, simple analysis algorithm, which incorporates the confocal properties of the OCT system, the light attenuation coefficients for these constituents were determined: for diffuse intimal thickening (5.5/spl plusmn/1.2 mm/sup -1/) and lipid-rich regions (3.2/spl plusmn/1.1 mm/sup -1/), the attenuation differed significantly from media (9.9/spl plusmn/1.8 mm/sup -1/), calcifications (11.1/spl plusmn/4.9 mm/sup -1/) and thrombi (11.2/spl plusmn/2.3 mm/sup -1/) (p<0.01). These proof of principle studies show that simple quantitative analysis of the OCT signals allows spatial determination of the intrinsic optical attenuation coefficient of atherosclerotic tissue components within regions of interest. Combining morphological imaging by OCT with the observed differences in optical attenuation coefficients of the various regions may enhance discrimination between various plaque types.

Measurement of the axial point spread function in scattering media using single-mode fiber-based optical coherence tomography

The authors studied the axial point spread function of optical coherence tomography for Gaussian intensity profiles emitted from and coupled back into single-mode fibers for signals from a scattering medium. The determined Rayleigh length of the axial point spread function was roughly twice the one measured from the reflection of a mirror. Using the measured point spread function in combination with the single backscatter model allowed determination of the attenuation coefficient of the suspension.

Comparative optical coherence tomography imaging of human esophagus: How accurate is localization of the muscularis mucosae?

BACKGROUND Early diagnosis of esophageal cancer limited to the mucosa allows local endoscopic treatment and thereby improves prognosis. Optical coherence tomography images of normal human esophageal tissue obtained with 2 systems with light sources that provide different wavelengths (800 nm and 1275 nm) were compared with histology to determine which wavelength is best suited for detailed optical coherence tomography imaging of the esophageal wall, and to precisely localize the muscularis mucosae. METHODS Within 1 hour of surgical resection, an esophageal specimen was cleaned of excess blood with saline solution and soaked in formalin for a minimum of 48 hours. After optical coherence tomography imaging, the specimen was prepared for routine histologic assessment. To precisely localize the different layers of the esophageal wall on an optical coherence tomography image, well-defined structures within the esophageal wall were sought. RESULTS The 1275 nm system with 12 mm resolution was superior in terms of imaging depth. As compared with histology, the 4 microm resolution of the 800 nm system made fine detail more visible. With minimal experience, the muscularis mucosae could be recognized with either system as a hyporeflective layer with a diameter of around 180 microm. CONCLUSIONS Based on appearance and location of morphologic landmarks, layers of normal esophageal wall, specifically, the location and extent of the muscularis mucosae, could be recognized by using both the 800 nm and 1275 nm optical coherence tomography system. Although different conditions may be operative in vivo, the present ex vivo study further verifies by precise interpretation that optical coherence tomography provides precise images of the esophageal wall.

Macular pigment optical density measurements: evaluation of a device using heterochromatic flicker photometry

PurposeAccurate assessment of the amount of macular pigment (MPOD) is necessary to investigate the role of carotenoids and their assumed protective functions. High repeatability and reliability are important to monitor patients in studies investigating the influence of diet and supplements on MPOD. We evaluated the Macuscope (Macuvision Europe Ltd., Lapworth, Solihull, UK), a recently introduced device for measuring MPOD using the technique of heterochromatic flicker photometry (HFP). We determined agreement with another HFP device (QuantifEye; MPS 9000 series: Tinsley Precision Instruments Ltd., Croydon, Essex, UK) and a fundus reflectance method.MethodsThe right eyes of 23 healthy subjects (mean age 33.9±15.1 years) were measured. We determined agreement with QuantifEye and correlation with a fundus reflectance method. Repeatability of QuantifEye was assessed in 20 other healthy subjects (mean age 32.1±7.3 years). Repeatability was also compared with measurements by a fundus reflectance method in 10 subjects.ResultsWe found low agreement between test and retest measurements with Macuscope. The average difference and the limits of agreement were −0.041±0.32. We found high agreement between test and retest measurements of QuantifEye (−0.02±0.18) and the fundus reflectance method (−0.04±0.18). MPOD data obtained by Macuscope and QuantifEye showed poor agreement: −0.017±0.44. For Macuscope and the fundus reflectance method, the correlation coefficient was r=0.05 (P=0.83). A significant correlation of r=0.87 (P<0.001) was found between QuantifEye and the fundus reflectance method.ConclusionsBecause repeatability of Macuscope measurements was low (ie, wide limits of agreement) and MPOD values correlated poorly with the fundus reflectance method, and agreed poorly with QuantifEye, the tested Macuscope protocol seems less suitable for studying MPOD.

Volumetric laser endomicroscopy in Barrett's esophagus: a feasibility study on histological correlation

Volumetric laser endomicroscopy (VLE) is a novel balloon-based optical coherence tomography (OCT) imaging technique that may improve detection of early neoplasia in Barretts esophagus (BE). Most OCT studies lack a direct correlation between histology and OCT images. The aim is to investigate the optimal approach for achieving one-to-one correlation of ex-vivo VLE images of endoscopic resection (ER) specimens with histology. BE patients with and without early neoplasia underwent ER after delineating areas with electrocoagulation markers (ECM). After ER, specimens underwent additional ex-vivo marking with several different markers (ink, pin, Gold Probe) followed by ex-vivo VLE scanning. ER specimens were carefully sectioned into tissue blocks guided by the markers. Histology and VLE slides were considered a match if ≥ 2 markers were visible on both modalities and mucosal patterns aside from these markers matched on both histology and VLE. From 16 ER specimens 120 tissue blocks were sectioned of which 23 contained multiple markers. Fourteen histology-VLE matches were identified. ECMs and ink markers proved to be the most effective combination for matching. The last 6/16 ER specimens yielded 9/14 matches, demonstrating a learning curve due to methodological improvements in marker placement and tissue block sectioning. One-to-one correlation of VLE and histology is complex but feasible. The groundwork laid in this study will provide high-quality histology-VLE correlations that will allow further research on VLE features of early neoplasia in BE.

Functional optical coherence tomography of pigmented lesions

Cutaneous melanomas are diagnosed worldwide in 231 130 patients per year. The sensitivity and specificity of melanoma diagnosis expresses the need for an additional diagnostic method. Optical coherence tomography (OCT) has shown that it allows morphological (qualitative) description of image features and quantitative analysis of pathology related light scattering by means of the attenuation coefficient (μoct).

Hematocrit-dependence of the scattering coefficient of blood determined by optical coherence tomography

We determined the scattering coefficient and scattering anisotropy of blood samples with varying hematocrit using optical coherence tomography measurements and a curve fitting procedure. Initial results show much lower scattering coefficient and scattering anisotropy than theoretically expected, which are likely attributed to the highly forward scattering nature of blood.

Single fiber reflectance spectroscopy calibration (Conference Presentation)

Broadband fiberoptic spectroscopy is investigated for diagnostic applications, based on its ability to noninvasively determine tissue scattering and absorption properties. Spectroscopic instrumentation requires a calibration to account for wavelength dependent factors that may vary, such as the output of the light source, fiberoptic coupling efficiency, ambient light, fiber transmission and detector sensitivity. For techniques such as Diffuse Reflectance Spectroscopy (DRS), a relative calibration of the reflectance is sufficient. For Single Fiber Reflectance spectroscopy (SFR), however, the measured absolute reflectance, R is related to the sample optical properties. Consequently, in order to extract tissue optical properties using SFR, an absolute calibration of the reflectance is required. We investigated two novel SFR calibration methods, using a calibrated mirror and using the Fresnel reflection at the measurement fiber tip as a reference. We compared these to commonly used calibration methods, using either Intralipid-20% in combination with Monte Carlo simulations or Spectralon as a reference. The Fresnel reflection method demonstrated the best reproducibility and yielded the most reliable result. We therefore recommend the Fresnel reflection method for the absolute reflectance calibration of SFR.

Spectral domain, common path OCT in a handheld PIC based system

Optical Coherence Tomography (OCT) has made it into the clinic in the last decade with systems based on bulk optical components. The next disruptive step will be the introduction of handheld OCT systems. Photonic Integrated Circuit (PIC) technology is the key enabler for this further miniaturization. PIC technology allows signal processing on a stable platform and the implementation of a common path interferometer in that same platform creates a robust fully integrated OCT system with a flexible fiber probe. In this work the first PIC based handheld and integrated common path based spectral domain OCT system is described and demonstrated. The spectrometer in the system is based on an Arrayed Waveguide Grating (AWG) and fully integrated with the CCD and a fiber probe into a system operating at 850 nm. The AWG on the PIC creates a 512 channel spectrometer with a resolution of 0.22 nm enabling a high speed analysis of the full A-scan. The silicon nitride based proprietary waveguide technology (TriPleXTM) enables low loss complex photonic structures from the visible (405 nm) to IR (2350 nm) range, making it a unique candidate for OCT applications. Broadband AWG operation from visible to 1700 nm has been shown in the platform and Photonic Design Kits (PDK) are available enabling custom made designs in a system level design environment. This allows a low threshold entry for designing new (OCT) designs for a broad wavelength range.

7 In vivo optisch coherente tomografie voor evaluatie van hogere urinewegurotheeltumoren – eerste resultaten van een pilotstudie

Tijdschrift voor Urologie mei 2013 nr. 3 Resultaten Zowel na behandeling met op TPCS2a gebaseerde fotodynamische therapie (PDT) alleen, als na behandeling met bleomycine of een van de controlechemotherapeutica alleen werd in alle 5 cellijnen een dosisafhankelijke inhibitie van celproliferatie gezien. Bij de combinatiebehandelingen werd enkel een significant (p < 0,001) synergistisch effect, dus een fotochemisch internalisatie-effect, geobserveerd voor PDT gecombineerd met bleomycine in de T24en de AY-27-cellijn.