Automatic assessment of time-resolved OCT images for selective retina therapy.

PURPOSE: In recent years, selective retina laser treatment (SRT), a sub-threshold therapy method, avoids widespread damage to all retinal layers by targeting only a few. While these methods facilitate faster healing, their lack of visual feedback during treatment represents a considerable shortcoming as induced lesions remain invisible with conventional imaging and make clinical use challenging. To overcome this, we present a new strategy to provide location-specific and contact-free automatic feedback of SRT laser applications. METHODS: We leverage time-resolved optical coherence tomography (OCT) to provide informative feedback to clinicians on outcomes of location-specific treatment. By coupling an OCT system to SRT treatment laser, we visualize structural changes in the retinal layers as they occur via time-resolved depth images. We then propose a novel strategy for automatic assessment of such time-resolved OCT images. To achieve this, we introduce novel image features for this task that when combined with standard machine learning classifiers yield excellent treatment outcome classification capabilities. RESULTS: Our approach was evaluated on both ex vivo porcine eyes and human patients in a clinical setting, yielding performances above 95 % accuracy for predicting patient treatment outcomes. In addition, we show that accurate outcomes for human patients can be estimated even when our method is trained using only ex vivo porcine data. CONCLUSION: The proposed technique presents a much needed strategy toward noninvasive, safe, reliable, and repeatable SRT applications. These results are encouraging for the broader use of new treatment options for neovascularization-based retinal pathologies.

Time-Resolved Ultra-High Resolution Optical Coherence Tomography for Real-Time Monitoring of Selective Retina Therapy.

PURPOSE: Selective retina therapy (SRT) is a novel treatment for retinal pathologies, solely targeting the RPE. During SRT, the detection of an immediate tissue reaction is challenging, as tissue effects remain limited to intracellular RPE photodisruption. Time-resolved ultra-high axial resolution optical coherence tomography (OCT) is thus evaluated for the monitoring of dynamic optical changes at and around the RPE during SRT. METHODS: An experimental OCT system with an ultra-high axial resolution of 1.78 µm was combined with an SRT system and time-resolved OCT M-scans of the target area were recorded from four patients undergoing SRT. Optical coherence tomography scans were analyzed and OCT morphology was correlated with findings in fluorescein angiography, fundus photography, and cross-sectional OCT. RESULTS: In cases in which the irradiation caused RPE damage proven by fluorescein angiography, the lesions were well discernible in time-resolved OCT images but remained invisible in fundus photography and cross-sectional OCT acquired after treatment. If RPE damage was introduced, all applied SRT pulses led to detectable signal changes in the time-resolved OCT images. The extent of optical signal variation seen in the OCT data appeared to scale with the applied SRT pulse energy. CONCLUSIONS: The first clinical results proved that successful SRT irradiation induces detectable changes in the OCT M-scan signal while it remains invisible in conventional ophthalmoscopic imaging. Thus, real-time high-resolution OCT is a promising modality to monitor and analyze tissue effects introduced by selective retina therapy and may be used to guide SRT in an automatic feedback mode (www.swissmedic.ch number, 2011-MD-0006).

Noninvasive referencing of intraocular tumors for external beam radiation therapy using optical coherence tomography: a proof of concept.

PURPOSE: External beam radiation therapy is currently considered the most common treatment modality for intraocular tumors. Localization of the tumor and efficient compensation of tumor misalignment with respect to the radiation beam are crucial. According to the state of the art procedure, localization of the target volume is indirectly performed by the invasive surgical implantation of radiopaque clips or is limited to positioning the head using stereoscopic radiographies. This work represents a proof-of-concept for direct and noninvasive tumor referencing based on anterior eye topography acquired using optical coherence tomography (OCT). METHODS: A prototype of a head-mounted device has been developed for automatic monitoring of tumor position and orientation in the isocentric reference frame for LINAC based treatment of intraocular tumors. Noninvasive tumor referencing is performed with six degrees of freedom based on anterior eye topography acquired using OCT and registration of a statistical eye model. The proposed prototype was tested based on enucleated pig eyes and registration accuracy was measured by comparison of the resulting transformation with tilt and torsion angles manually induced using a custom-made test bench. RESULTS: Validation based on 12 enucleated pig eyes revealed an overall average registration error of 0.26 ± 0.08° in 87 ± 0.7 ms for tilting and 0.52 ± 0.03° in 94 ± 1.4 ms for torsion. Furthermore, dependency of sampling density on mean registration error was quantitatively assessed. CONCLUSIONS: The tumor referencing method presented in combination with the statistical eye model introduced in the past has the potential to enable noninvasive treatment and may improve quality, efficacy, and flexibility of external beam radiotherapy of intraocular tumors.

Influence and compensation of autocorrelation terms in depth-resolved spectroscopic Fourier-domain optical coherence tomography.

We demonstrate depth-resolved spectral absorption measurements in the wavelength range from 750 to 850 nm using a broadband light source consisting of three spectrally shifted superluminescent light-emitting diode modules and a low-cost spectrometer-based Fourier-domain optical coherence tomography system. We present the theoretical model and experimental verification of interferences between autocorrelation terms and the signal carrying cross-correlation terms, strongly affecting the absorption measurements. A simple background subtraction, minimizing the artifacts caused by the interferences of autocorrelation and cross-correlation terms, is presented.

Autoantibodies against bactericidal/permeability-increasing protein (BPI) in children with acute pneumonia.

Antineutrophil cytoplasmic antibodies directed against bactericidal/permeability-increasing protein (BPI), an inhibitor of a lipopolysaccharide of gram-negative bacteria, are a common feature of chronic neutrophilic inflammatory processes such as cystic fibrosis. We investigated whether serum and salivary anti-BPI autoantibodies also appear in the course of acute pneumonia in 24 otherwise healthy children. Nine (38%) and four (17%) patients had detectable serum anti-BPI immunoglobulin G (IgG) (> or =4 IU mL(-1)) and IgA (ratio> or =1.2), respectively, on the day of hospital admission (day 0). There was no increase in the rate of occurrence or the concentration of these antibodies in the convalescent sera obtained on day 30. The presence of anti-BPI IgG on admission did not correlate with inflammatory markers (peripheral white blood cell count, C-reactive protein) or temperature on admission. Also, salivary anti-BPI IgA, determined on days 0, 3-5 and 30, did not appear during the course of acute pneumonia. In summary, a substantial proportion of previously healthy children have pre-existing anti-BPI IgG autoantibodies. Acute neutrophilic infection, i.e. pneumonia, however, neither triggered the appearance of new antibodies nor boosted the concentrations of pre-existing ones. Thus, in typical acute pneumonia in children, autoantibodies directed against BPI may not have clinical significance.