Dirk J. Faber

Recent developments in optical coherence tomography for imaging the retina

Optical coherence tomography (OCT) was introduced in ophthalmology a decade ago. Within a few years in vivo imaging of the healthy retina and optic nerve head and of retinal diseases was a fact. In particular the ease with which these images can be acquired considerably changed the diagnostic strategy used by ophthalmologists. The OCT technique currently available in clinical practice is referred to as time-domain OCT, because the depth information of the retina is acquired as a sequence of samples, over time. This can be done either in longitudinal cross-sections perpendicular to, or in the coronal plane parallel to the retinal surface. Only recently, major advances have been made as to image resolution with the introduction of ultrahigh resolution OCT and in imaging speed, signal-to-noise ratio and sensitivity with the introduction of spectral-domain OCT. Functional OCT is the next frontier in OCT imaging. For example, polarization-sensitive OCT uses the birefringent characteristics of the retinal nerve fibre layer to better assess its thickness. Blood flow information from retinal vessels as well as the oxygenation state of retinal tissue can be extracted from the OCT signal. Very promising are the developments in contrast-enhanced molecular optical imaging, for example with the use of scattering tuneable nanoparticles targeted at specific tissue or cell structures. This review will provide an overview of these most recent developments in the field of OCT imaging focussing on applications for the retina.

Light absorption of (oxy-)hemoglobin assessed by spectroscopic optical coherence tomography

The combination of optical coherence tomography and spectroscopy may allow for highly localized, quantitative measurements of tissue spectral properties. We present, for the first time to our knowledge, quantitative measurements of the absorption coefficients of phantoms and of hemoglobin and oxygenated hemoglobin with spectroscopic optical coherence tomography (SOCT). Our results suggest that SOCT will be able to provide localized, quantitative oxygenation measurements.

A New Generation of Optical Diagnostics for Bladder Cancer: Technology, Diagnostic Accuracy, and Future Applications

CONTEXT New developments in optical diagnostics have a potential for less invasive and improved detection of bladder cancer. OBJECTIVE To provide an overview of the technology and diagnostic yield of recently developed optical diagnostics for bladder cancer and to outline their potential future applications. EVIDENCE ACQUISITION A PubMed literature search was performed, and papers on Raman spectroscopy (RS), optical coherence tomography (OCT), photodynamic diagnosis (PDD) and narrow-band imaging (NBI) regarding bladder cancer were reviewed. Technology, clinical evidence, and future applications of the techniques are discussed. EVIDENCE SYNTHESIS With RS, the molecular components of tissue can be measured objectively in qualitative and quantitative ways. The first studies demonstrating human in vivo applicability are still awaited. OCT produces high-resolution, cross-sectional images of tissue, comparable with histopathology, and provides information about depth of tumour growth. The first in vivo studies of OCT demonstrated promising diagnostic accuracy. RS and OCT are not suitable for scanning the entire bladder. PDD is a technique using fluorescence to indicate pathologic tissue. Several studies have shown that PDD increases the detection rate of bladder tumours and improves resection, resulting in fewer early recurrences. The relatively low specificity of PDD remains a problem. NBI enhances contrast of mucosal surface and microvascular structures. The NBI technique has clear advantages over PDD, and the two studies published to date have shown promising preliminary results. PDD and NBI do not contribute to histopathologic diagnosis. CONCLUSIONS RS and OCT aim at providing a real-time, minimally invasive, objective prediction of histopathologic diagnosis, while PDD and NBI aim at improving visualisation of bladder tumours. For RS, OCT, and NBI, more research has to be conducted before these techniques can be implemented in the management of bladder cancer. All techniques might be of value in specific clinical scenarios.

Toward assessment of blood oxygen saturation by spectroscopic optical coherence tomography

The use of spectroscopic optical coherence tomography to assess hemoglobin oxygen saturation of whole blood is investigated. We propose to use the differential attenuation coefficient to determine the degree of saturation. Our data show qualitative agreement between the measured differential attenuation coefficients as a function of saturation and predictions based on the oxygen-saturation-dependent absorption and scattering properties of blood.

Are quantitative attenuation measurements of blood by optical coherence tomography feasible

We present optical coherence tomography (OCT) measurements on fully physiologically oxygenated blood samples of varying hematocrit. We show that attenuation coefficients cannot be extracted quantitatively using the currently accepted models for the OCT signal from scattering media, because the confidence intervals obtained in the fitting procedure cannot be used as reliable uncertainty estimates of the attenuation coefficients. Better modeling of the hematocrit-dependent OCT signal is needed.

Quantitative comparison of the OCT imaging depth at 1300 nm and 1600 nm

One of the present challenges in optical coherence tomography (OCT) is the visualization of deeper structural morphology in biological tissues. Owing to a reduced scattering, a larger imaging depth can be achieved by using longer wavelengths. In this work, we analyze the OCT imaging depth at wavelengths around 1300 nm and 1600 nm by comparing the scattering coefficient and OCT imaging depth for a range of Intralipid concentrations at constant water content. We observe an enhanced OCT imaging depth for 1600 nm compared to 1300 nm for Intralipid concentrations larger than 4 vol.%. For higher Intralipid concentrations, the imaging depth enhancement reaches 30%. The ratio of scattering coefficients at the two wavelengths is constant over a large range of scattering coefficients and corresponds to a scattering power of 2.8 ± 0.1. Based on our results we expect for biological tissues an increase of the OCT imaging depth at 1600 nm compared to 1300 nm for samples with high scattering power and low water content.

Volumetric In-Vivo Visualization of Upper Urinary Tract Tumors Using Optical Coherence Tomography: A Pilot Study

PURPOSE Knowledge of tumor stage and grade is paramount for treatment decision making in cases of upper urinary tract urothelial carcinoma but this condition cannot be accurately assessed by current techniques. Optical coherence tomography can hypothetically provide the urologist with real-time intraoperative information on tumor grade and stage. In this pilot study we report what are to our knowledge the first results of optical coherence tomography for grading and staging upper urinary tract urothelial carcinoma. MATERIALS AND METHODS Eight consecutive patients underwent ureterorenoscopy for suspicion or followup of upper urinary tract urothelial carcinoma. Optical coherence tomography data sets were intraoperatively obtained from the ureter and renal pelvis. All patients eventually underwent nephroureterectomy. Optical coherence tomography staging was done by visual inspection of lesions found on optical coherence tomography images. Optical coherence tomography grading was done by quantifying optical coherence tomography signal attenuation in mm(-1) on lesions and comparing results with the histopathological diagnosis. The Wilcoxon rank sum test was used for statistical analysis. RESULTS For 7 in vivo optical coherence tomography diagnoses staging was in accordance with histology. In patient 8 tumor thickness transcended optical coherence tomography imaging depth range and, therefore, invasiveness findings were inconclusive. For grading the median attenuation coefficient for grade 2 and 3 lesions was 1.97 (IQR 1.57-2.30) and 3.53 mm(-1) (IQR 2.74-3.94), respectively (p<0.001). Healthy urothelium was too thin to reliably determine the attenuation coefficient. CONCLUSIONS Optical coherence tomography is a promising, minimally invasive tool for real-time intraoperative optical diagnosis of tumors in the upper urinary tract. Our results warrant future research in a larger sample size to determine the accuracy of grading and staging by optical coherence tomography, and its possible implementation in the diagnostic algorithm for upper urinary tract urothelial carcinoma.

Differentiation between normal renal tissue and renal tumours using functional optical coherence tomography: a phase I in vivo human study.

Whats known on the subject? and What does the study add?

Integrated system for combined Raman spectroscopy-spectral domain optical coherence tomography

Raman spectroscopy (RS) and optical coherence tomography (OCT) are powerful tools for optical analysis of tissues with mutually complementary strengths and limitations. OCT excels at visualizing tissue microstructure but lacks molecular specificity, while RS can relay tissue biochemical composition but typically cannot relate microstructure. Previous implementations of combined RS-OCT have utilized a common sample arm while maintaining independent RS and OCT detection arms. We present the design and application of an integrated RS-OCT instrument with a common detection arm for both RS and OCT. The detector is a spectrograph capable of sequential detection of the 855-nm OCT signal and the Raman scatter generated by a 785-nm source. The capabilities of the instrument are demonstrated ex vivo in the calvaria and retina of rodents, as well as in vivo in human skin.

Multiple and dependent scattering effects in Doppler optical coherence tomography

Doppler optical coherence tomography (OCT) is a technique to image tissue morphology and to measure flow in turbid media. In its most basic form, it is based on single (Mie) scattering. However, for highly scattering and dense media multiple and concentration dependent scattering can occur. For Intralipid solutions with varying scattering strength, the effect of multiple and dependent scattering on the OCT signal attenuation and Doppler flow is investigated. We observe a non-linear increase in the OCT signal attenuation rate and an increasingly more distorted Doppler OCT flow profile with increasing Intralipid concentration. The Doppler OCT attenuation and flow measurements are compared to Monte Carlo simulations and good agreement is observed. Based on this comparison, we determine that the single scattering attenuation coefficient micros is 15% higher than the measured OCT signal attenuation rate. This effect and the distortion of the measured flow profile are caused by multiple scattering. The non-linear behavior of the single scattering attenuation coefficient with Intralipid concentration is attributed to concentration dependent scattering.