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Denosumab is an established targeted systemic therapy for treatment of giant cell tumor of bone (GCTB). We sought to determine whether treatment response could be quantified from radiomics analysis of radiographs taken longitudinally during treatment. Pre- and post-treatment radiographs of 10 GCTB tumors from 10 patients demonstrating histologic response after treatment with denosumab were analyzed. Intensity- and texture-based radiomics features for each manually segmented tumor were calculated. Radiomics features were compared pre- and post-treatment in tumors. Mean intensity (p = 0.033) significantly increased while skewness (p = 0.028) significantly decreased after treatment. Post-treatment increases in fractal dimensions (p = 0.057) and abundance (p = 0.065) approached significance. A potential linear correlation in mean (p = 0.005; ΔMean = 0.022 * duration − 0.026) with treatment duration was observed. Radiomics analysis of plain radiographs quantifies time-dependent matrix mineralization and trabecular reconstitution that mark positive response of giant cell tumors of bone to denosumab.

We have combined an anterior segment (AS) optical coherence tomography (OCT) system and a wavefront-based aberrometer with an approach that senses ocular wavefront aberrations using the OCT beam. Temporal interlacing of the OCT and aberrometer channels allows for OCT images and refractive error measurements to be acquired continuously and in real-time. The system measures refractive error with accuracy and precision comparable to that of clinical autorefractors. The proposed approach provides a compact modular design that is suitable for integrating OCT and wavefront-based autorefraction within the optical head of the ophthalmic surgical microscope for guiding cataract surgery or table-top devices for simultaneous autorefraction and ocular biometry.

In an effort to meet the need of imaging technology that reliably measure the dynamics of accommodation, we developed a swept source OCT system for imaging and biometry of the crystalline lens dynamics at high sampling rates (~100 Hz). Preliminary data suggests that high sampling rates improve detection of lens micro-fluctuations during accommodation and that sampling rates higher than 40 Hz might be needed to fully capture crystalline lens dynamics. Long term, the information acquired with the system will improve our understanding of the mechanism of accommodation and enable to design and evaluate new procedures to restore accommodation.

A procedure for identification of optimal Apparent Diffusion Coefficient (ADC) thresholds for automatic delineation of prostatic lesions with restricted diffusion at differing risk for cancer was developed. The relationship between the size of the identified Volumes of Interest (VOIs) and Gleason Score (GS) was evaluated. Patients with multiparametric (mp)MRI, acquired prior to radical prostatectomy (RP) (n = 18), mpMRI-ultrasound fused (MRI-US) (n = 21) or template biopsies (n = 139) were analyzed. A search algorithm, spanning ADC thresholds in 50 µm2/s increments, determined VOIs that were matched to RP tumor nodules. Three ADC thresholds for both peripheral zone (PZ) and transition zone (TZ) were identified for estimation of VOIs at low, intermediate, and high risk of prostate cancer. The determined ADC thresholds for low, intermediate and high risk in PZ/TZ were: 900/800; 1100/850; and 1300/1050 µm2/s. The correlation coefficients between the size of the high/intermediate/low risk VOIs and GS in the three cohorts were 0.771/0.778/0.369, 0.561/0.457/0.355 and 0.423/0.441/0.36 (p

We present a new in vitro instrument for measuring shape and wavefront aberrations of the primate crystalline lens, both on- and off-axis, while simulating accommodation with a motorized lens stretching system. The instrument merges spectral domain optical coherence tomography (SD-OCT) imaging and ray tracing aberrometry using an approach that senses wavefront aberrations of the lens with the OCT probing beam. Accuracy and repeatability of aberration measurements were quantified. Preliminary experiments on two human and four cynomolgus monkey lenses demonstrate the ability of the system to measure the lens shape, spherical aberration and peripheral defocus, and their changes during simulated accommodation.

Purpose: To objectively quantify dynamic changes in lens shape during accommodation using two-dimensional OCT images Methods: In-vivo responses to an accommodative step stimulus of three subjects (aged 22, 39, and 45) were captured using a custom-made extended-depth SD-OCT system operating at 840 nm following an IRB-approved protocol (Ruggeri et al. 2012). Subjects focused on a visual accommodation target designed to produce an adjustable step stimulus of accommodation. Accommodative responses to 2-D and 4-D stimuli were captured ~1.5s before and ~4.5s after stimulation. Lens thickness, anterior curvature, and posterior curvature were measured using a newly-developed algorithm (validated using a calibration sphere). Dynamic changes in lens thickness and curvature were then fitted with an exponential model to produce time dependent constants. Results: All calibration OCT images were automatically analyzed in under 2 seconds. A radius of 7.793mm ± 0.051mm was calculated resulting in a difference of 2.4μm from the reported nominal value of the calibration sphere. Anterior lens radius decreased over time in all subjects. Radius of the posterior lens experienced a slight increase for all subjects. Conclusion: This study demonstrates the feasibility of quantifying the dynamic changes in lens curvature and thickness during accommodation using extended-depth OCT combined with a step accommodation stimulus and an automated segmentation algorithm.

Optical coherence tomography (OCT) offers new options for imaging the ciliary muscle allowing direct in vivo visualization. However, variation in image quality along the length of the muscle prevents accurate delineation and quantification of the muscle. Quantitative analyses of the muscle are accompanied by variability in segmentation between examiners and between sessions for the same examiner. In processes such as accommodation where changes in muscle thickness may be tens of microns- the equivalent of a small number of image pixels, differences in segmentation can influence the magnitude and potentially the direction of thickness change. A detailed analysis of variability in ciliary muscle thickness measurements was performed to serve as a benchmark for the extent of this variability in studies on the ciliary muscle. Variation between sessions and examiners were found to be insignificant but the magnitude of variation should be considered when interpreting ciliary muscle results.

Purpose: To determine the dynamic interaction between ciliary muscle and lens during accommodation and disaccommodation through synchronous imaging of ciliary muscle and lens response to pulse stimulus Methods: The ciliary muscle and lens were imaged simultaneously in a 33 year old subject responding to a 4D pulse stimulus (accommodative stimulus at 1.7 s, disaccommodative stimulus at 7.7 s) using an existing imaging system (Ruggeri et al, 2016) consisting of an Anterior Segment Optical Coherence Tomography system, Ciliary Muscle Optical Coherence Tomography system, and custom-built accommodation module. OCT images were recorded at an effective frame rate of 13.0 frames per second for a total scan time of 11.5 s. An automated segmentation algorithm was applied to images of the anterior segment to detect the boundaries of the cornea and lens, from which lens thickness was extracted. Segmentation of the ciliary muscle was performed manually and then corrected for distortion due to refraction of the beam to obtain measurements of thicknesses at the apex and fixed distances from the scleral spur. Results: The dynamic biometric response to a pulse stimulus at 4D was determined for both the ciliary muscle and lens, suggesting the ciliary muscle and lens interact differently in accommodation and disaccommodation. Conclusions: The study introduces new data and analyses of the ciliary muscle and lens interaction during a complete accommodative response from the relaxed to the accommodated state and back, providing insight into the interplay between individual elements in the accommodative system and how their relationships may change with age.

Age-related changes in the crystalline lens shape and refractive index gradient produce changes in dioptric power and high-order aberrations that influence the optics of the whole eye and contribute to a decrease in overall visual quality. Despite their key role, the changes in lens shape and refractive index gradient with age and accommodation and their effects on high-order aberrations are still not well understood. The goal of this project was to develop a combined laser ray tracing (LRT) and optical coherence tomography (OCT) system to measure high-order aberrations, shape and refractive index gradient in non-human primate and human lenses. A miniature motorized lens stretching system was built to enable imaging and aberrometry of the lens during simulated accommodation. A positioning system was also built to enable on- and off-axis OCT imaging and aberrometry for characterization of the peripheral defocus of the lens. We demonstrated the capability of the LRT-OCT system to produce OCT images and aberration measurements of crystalline lens with age and accommodation in vitro. In future work, the information acquired with the LRT-OCT system will be used to develop an accurate age-dependent lens model to predict the role of the lens in the development of refractive error and aberrations of the whole eye.

The lens equivalent refractive index (RI) is commonly used in calculations of crystalline lens power. However, accurate determination of the equivalent RI in vivo is challenging due to the need of multiple measurements with different ocular biometry devices. A custom extended-depth Spectral Domain-OCT system was utilized to provide measurements of corneal and lens surface curvatures and all intraocular distances required for determination of the lens equivalent RI. Ocular biometry and refraction were input into a computational model eye from which the equivalent RI was calculated. Results derived from human subjects of a wide age range show a decrease in RI with age and demonstrate the capability of in vivo measurements of the equivalent RI with extended-depth OCT.

Two SD-OCT systems and a dual channel accommodation target were combined and precisely synchronized to simultaneously image the anterior segment and the ciliary muscle during dynamic accommodation. The imaging system simultaneously generates two synchronized OCT image sequences of the anterior segment and ciliary muscle with an imaging speed of 13 frames per second. The system was used to acquire OCT image sequences of a non-presbyopic and a pre-presbyopic subject accommodating in response to step changes in vergence. The image sequences were processed to extract dynamic morphological data from the crystalline lens and the ciliary muscle. The synchronization between the OCT systems allowed the precise correlation of anatomical changes occurring in the crystalline lens and ciliary muscle at identical time points during accommodation. To describe the dynamic interaction between the crystalline lens and ciliary muscle, we introduce accommodation state diagrams that display the relation between anatomical changes occurring in the accommodating crystalline lens and ciliary muscle.

Purpose: To assess the long-term outcomes of astigmatic keratotomy (AK) performed with two different techniques in patients with post-penetrating keratoplasty (post-PK) residual astigmatism. Methods: This retrospective comparative case series was performed at Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA. Patients who underwent post-PK AK performed using either 30 kHz femtosecond laser flap mode software (IntraLase/AMO, Irvine, CA)-Group 1-or using 150 kHz femtosecond laser enabled AK software (IntraLase/AMO, Irvine, CA)-Group 2-to create two anterior arcuate corneal incisions were included in this study. Preoperative and long-term postoperative follow-up data, including uncorrected distance visual acuity (UDVA), corrected distance visual acuity (CDVA), and spherical equivalence (SE) were analyzed. Results: In group 1 (n=5), the difference in pre- and post-operative UDVA (0.97 ± 0.29 LogMAR to 0.68 ± 0.40 LogMAR, p=0.13), CDVA (0.28 ± 0.27 LogMAR to 0.47 ± 0.48 LogMAR, p=1), SE (-2.0 ± 3.0 diopters (D) to -1.8 ± 1.8 D, p=0.88) were not statistically significant, although UDVA and SE showed clinical improvement. In group 2 (n=6), the difference in pre- and post-operative UDVA (1.20 ± 0.14 LogMAR to 0.82 ± 0.62 LogMAR, p=0.19), CDVA (0.58 ± 0.32 LogMAR to 0.34 ± 0.31 LogMAR, p=0.25), SE (-2.3 ± 4.7 D to -2.9 ± 4.4 D, p=0.25) were not statistically significant. There was no statistical difference regarding postoperative UDVA (p=0.85), CDVA (p=0.93), SE (p=0.51) and surgically induced astigmatism (p=0.13) between the 2 groups. Conclusion: AK performed with both techniques is a safe procedure to correct post-PK residual astigmatism. Both techniques yielded comparable results.

Purpose: To determine an automatic procedure for determining the number and delineation of tumor habitats from Dynamic Contrast Enhanced (DCE) MRI data. Methods: An automatic procedure for delineation of tumor habitats from DCE-MRI datasets was developed as a two-part process involving: (1) statistical testing of the principal components of the dataset to detect the number of habitats and (2) the use of this number in an unsupervised pattern recognition (PR) technique to recover the temporal pattern and location of detected habitats. The procedure was tested on simulated DCE-MRI datasets with one, two, and three unique temporal patterns, corresponding to well-perfused, hypoxic, and necrotic tumor environments, at various noise levels. Recovery of the temporal pattern and location of detected habitats was tested on a separate simulated DCE-MRI dataset mimicking tumors with three unique habitats present in mixed proportions in each voxel of the dataset at different noise levels. The automatic procedure for delineation of tumor habitats was then applied to a DCE-MRI dataset from a preclinical prostate cancer tumor model and a soft tissue adult fibrosarcoma. Results: Statistical testing of the principal components of the simulated DCE-MRI datasets revealed correct estimation of the number of habitats in 99.6%, 99.5%, 99.7%, and 99.6% of trials (1000 total trials) when signal-to-noise ratio was 10, 7.5, 5, and 2.5, respectively. Recovery of the temporal pattern and location of tumor habitats from simulated DCE-MRI datasets using the unsupervised PR technique produced the three habitats used in the simulation with good fidelity at all noise levels. The automatic procedure for delineation of tumor habitats revealed three unique temporal patterns in the experimental rat model, resembling wellperfused, hypoxic, and necrotic habitats. Conclusion: The number of underlying tumor habitats can be determined using the automatic procedure, allowing potential use for finding hypoxic habitats indicative of worse patient outcomes.