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  • Accuracy of the TurfTrax Racing Data System for determination of equine speed and position.

    8 August 2018

    REASONS FOR PERFORMING STUDY: The speed and position data collected by TurfTrax Racing Data Limited during UK Thoroughbred racing have potential to benefit equine science and welfare. The size (the 2006 data set alone consists of 30,932 individual horse starts across 2667 races) and nature (speed and 2D position for each horse at 4 updates per second) of the data make it a unique resource for questions in equine safety, welfare, performance, and animal locomotion. OBJECTIVE: To determine the accuracy of the TurfTrax tracking system in estimating the speed and position of horses during racing. METHODS: Measurements from the TurfTrax wireless tracking system were compared with those of a survey-grade global positioning system (GPS) receiver. RESULTS: The TurfTrax system was found to give position measurements to within +/- 11 and +/- 64 cm in the fore-aft and lateral directions, respectively, averaging +/- 38 cm (interquartile range) and speed to within 0.15 m/s. POTENTIAL RELEVANCE: The data collected by the TurfTrax system are of sufficient accuracy to inform new diagnoses, training regimens and basic locomotor scientific studies. The position data can provide the precise distance, going, inclination, rate of turn and pack positioning through which each horse has raced. The speed profile can be used to examine the level of exertion, effect of training regimens and influence of racecourse features on performance. A first clinical application would be to analyse retrospectively these factors on occurrence of injury to compare with past training regimens, levels of exertion, and/or racecourse conditions.

  • Mesopic and dark-adapted two-color fundus-controlled perimetry in patients with cuticular, reticular, and soft drusen.

    8 August 2018

    PURPOSE: To examine the feasibility and utility of dark-adapted two-color fundus-controlled perimetry (FCP) in patients with cuticular, reticular, and soft drusen, and to compare FCP data to microstructural spectral-domain optical coherence tomography (SD-OCT) data. METHODS: Forty-four eyes (24 eyes of 24 patients with drusen, age 69.4 ± 12.6 years; 20 normal eyes of 16 subjects, 61.7 ± 12.4 years) underwent duplicate mesopic, dark-adapted cyan and dark-adapted red FCP within 14° of the central retina (total of 12 936 threshold tests) using the Scotopic Macular Integrity Assessment (S-MAIA, CenterVue, Padova, Italy) device. FCP data were registered to SD-OCT data to obtain outer nuclear layer, inner and outer photoreceptor segment, and retinal pigment epithelium drusen complex (RPEDC) thickness data spatially corresponding to the stimulus location and area (0.43°). Structure-function correlations were assessed using mixed-effects models. RESULTS: Mean deviation values for eyes with cuticular, soft, and reticular drusen were similar for mesopic (-2.1, -3.4, and -3.6 dB) and dark-adapted red (-1.4, -2.6, and -3.3 dB) FCP. For the dark-adapted cyan FCP (0.1, -1.9, and -5.0 dB) and for the cyan-red sensitivity difference (+1.0, +0.5, and -2.4 dB), the mean deviation values differed significantly in dependence of the predominant drusen type (one-way ANOVA; p < 0.05). RPEDC thickness was associated with reduction of mesopic sensitivity (-0.34 dB/10 µm RPEDC thickening; p < 0.001), dark-adapted cyan sensitivity (-0.11 dB/10 µm RPEDC thickening; p = 0.003), and dark-adapted red sensitivity (-0.26 dB/10 µm RPEDC thickening; p < 0.001). CONCLUSIONS: In contrast to mesopic FCP, dark-adapted two-color FCP allowed for meaningful differential testing of rod and cone function in patients with drusen indicating predominant cone dysfunction in eyes with cuticular drusen and predominant rod dysfunction in eyes with reticular drusen. RPEDC thickness was the strongest predictor of the evaluated SD-OCT biomarkers for point-wise sensitivity.

  • Structural Changes in Optical Coherence Tomography Underlying Spots of Increased Autofluorescence in the Perilesional Zone of Geographic Atrophy.

    8 August 2018

    Purpose: To investigate structural correlates corresponding to the appearance of increased fundus autofluorescence (FAF) in the perilesional area of geographic atrophy (GA) secondary to age-related macular degeneration. Methods: Serial FAF images of 181 eyes with GA of 134 patients participating in the Directional Spread in Geographic Atrophy study (NCT02051998) were screened for increased FAF spots that had developed during the review period. Thickness and reflectivity of the retinal pigment epithelium (RPE)-basal lamina complex, as well as the integrity of the external limiting membrane (ELM) and the ellipsoid zone (EZ), respectively, in corresponding optical coherence tomography (OCT) scans were compared between the time points before and after the appearance of increased FAF. Adjacent areas without development of abnormal FAF were assessed as internal control. Results: A total of 36 areas (15 eyes) with de novo developed increased FAF spots and 54 control areas were included. Analysis of the corresponding OCT images revealed an increase in RPE-basal lamina complex thickness (31.8 ± 7.3 to 42.1 ± 11.9 μm [P < 0.001]) and reflectivity (reflectivity ratio: 1.42 ± 0.11 to 1.54 ± 0.27 [P = 0.009]) corresponding to an increased FAF signal while there was no significant change in control areas. Development of increased FAF spots was associated with disruption of the ELM and the EZ. Conclusions: Increase of RPE-basal lamina complex thickness and reflectivity was spatially and temporally associated with the development of increased FAF spots in eyes with GA. In addition, outer retinal disruption may contribute to the corresponding increased FAF signal.

  • Effective Dynamic Range and Retest Reliability of Dark-Adapted Two-Color Fundus-Controlled Perimetry in Patients With Macular Diseases.

    8 August 2018

    Purpose: To determine the effective dynamic range (EDR), retest reliability, and number of discriminable steps (DS) for mesopic and dark-adapted two-color fundus-controlled perimetry (FCP) using the S-MAIA (Scotopic-Macular Integrity Assessment) "micro-perimeter." Methods: In this prospective cross-sectional study, each of the 52 eyes of 52 subjects with various macular diseases (mean age 62.0 ± 16.9 years; range, 19.1-90.1 years) underwent duplicate mesopic (achromatic stimuli, 400-800 nm), dark-adapted cyan (505 nm), and dark-adapted red (627 nm) FCP using a grid of 61 stimuli covering 18° of the central retina. The EDR, the number of DS, and the retest reliability for point-wise sensitivity (PWS) were analyzed. The effects of fixation stability, sensitivity, and age on retest reliability were examined using mixed-effects models. Results: The EDR was 10 to 30 dB with five DS for mesopic and 4 to 17 dB with four DS for dark-adapted cyan and red testing. PWS retest reliability was good among all three types of retinal sensitivity assessments (coefficient of repeatability ±5.79, ±4.72, and ±4.77 dB, respectively) and did not depend on fixation stability or age. PWS had no effect on retest variability in dark-adapted cyan and dark-adapted red testing but had a minor effect in mesopic testing. Conclusions: Combined mesopic and dark-adapted two-color FCP allows for reliable topographic testing of cone and rod function in patients with various macular diseases with and without foveal fixation. Retest reliability is homogeneous across eccentricities and various degrees of scotoma depth, including zones at risk for disease progression. These reliability estimates can serve for the design of future clinical trials.

  • Green-Light Autofluorescence Versus Combined Blue-Light Autofluorescence and Near-Infrared Reflectance Imaging in Geographic Atrophy Secondary to Age-Related Macular Degeneration.

    8 August 2018

    Purpose: To compare the intermodality and interreader agreement for geographic atrophy (GA) lesion size quantification in green-light fundus autofluorescence (GAF; excitation = 518 nm) versus combined blue-light fundus autofluorescence (BAF; excitation = 488 nm) and near-infrared reflectance (NIR; 820 nm) -based grading. Methods: Confocal scanning laser ophthalmoscopy (cSLO) GAF, BAF, and NIR images of 40 eyes from 29 patients (mean age 79.7 years) with GA secondary to AMD were recorded according to a standardized protocol. GA areas were analyzed in GAF, BAF combined with NIR (BAF+NIR), or BAF alone, by four independent readers using semiautomated software (RegionFinder; Heidelberg Engineering, Heidelberg, Germany). A mixed-effects model was used to assess the effect of image modality on the measured square-root lesion area. The coefficient of repeatability (CR) and intraclass correlation coefficient (ICC) were assessed for the square-root lesion area, lesion perimeter, and circularity. Results: GAF-based measurements were on average 0.062 mm (95% confidence interval [CI] 0.04-0.08 mm) larger than BAF+NIR-based measurements and 0.077 mm (95% CI 0.06 - 0.10 mm) larger than BAF-based measurements. Interreader agreement was highest for GAF-based analysis ([CR, ICC] 0.196 mm, 0.995) followed by BAF+NIR (0.232 mm, 0.992) and BAF alone (0.263 mm, 0.991). The same was noted for the lesion perimeter and circularity. Post hoc review revealed that interreader differences were associated with media opacification interfering with lesion boundary demarcation to a larger extent in BAF than in GAF. Conclusions: cSLO-based GAF and combined BAF+NIR imaging with semiautomated lesion delineation allow for an accurate and reproducible quantification of GA. The slightly better interreader agreement using cSLO GAF suggests that its use may be preferable in clinical trials examining the change in lesion size as a clinical endpoint.

  • Androgen receptor modulation does not affect longitudinal growth of cultured fetal rat metatarsal bones.

    8 August 2018

    BACKGROUND: Systemic administration of the nonaromatizable androgen oxandrolone stimulates growth in girls with Turner syndrome and boys with a constitutional delay of growth and puberty. It is unknown if oxandrolone acts locally at the growth plate level to stimulate longitudinal bone growth. METHODS: Metatarsal bones from female and male rat fetuses (day E20) were cultured for 14 days in the presence of oxandrolone, testosterone or the androgen receptor (AR) antagonist flutamide with/without insulin-like growth-factor-I (IGF-I) or charcoal-treated serum. RESULTS: The AR was found to be expressed in both male and female fetal rat metatarsal bones. Neither oxandrolone nor testosterone had any effect on metatarsal bone growth when tested at a wide concentration range (1 nM to 10 microM), not even in the presence of IGF-I (100 ng/ml) or charcoal-treated serum (10%). Bone growth was also unaffected when the AR was blocked by flutamide. Control experiments confirmed that metatarsal bone growth was significantly stimulated by IGF-I (p < 0.001). CONCLUSION: Modulation of AR activity in the fetal rat growth plate does not affect linear bone growth. Extrapolating from these in vitro data, it could be speculated that oxandrolone stimulates longitudinal bone growth in treated children by acting indirectly rather than directly through AR activation in growth plate chondrocytes.

  • Technical foundations and pitfalls of clinical fMRI.

    8 August 2018

    Magnetic resonance imaging (MRI) has become an established and invaluable tool in the diagnosis of numerous diseases through its ability to show pathologic contrast in images of soft tissue. More recently, MRI has found application in the study of organ function, principally in the brain and heart. This article deals with MRI imaging of brain function and describes some of the techniques that allow physiological parameters such as cerebral blood volume, cerebral blood oxygenation, and cerebral perfusion to be determined. Additionally, some of the potentially confounding influences in these experiments are discussed.

  • Centric ordering is superior to gradient moment nulling for motion artifact reduction in EPI.

    8 August 2018

    Echo-planar imaging (EPI) is sensitive to motion despite its rapid data acquisition rate. Compared with traditional imaging techniques, it is more sensitive to motion or flow in the phase-encode direction, which can cause image artifacts such as ghosting, misregistration, and loss of spatial resolution. Consequently, EPI of dynamic structures (eg, the cardiovascular system) could benefit from methods that eliminate these artifacts. In this paper, two methods of artifact reduction for motion in the phase-encode direction are evaluated. First, the k-space trajectory is evaluated by comparing centric with top-down ordered sequences. Next, velocity gradient moment nulling (GMN) of the phase-encode direction is evaluated for each trajectory. Computer simulations and experiments in flow phantoms and rabbits in vivo show that uncompensated centric ordering produces the highest image quality. This is probably due to a shorter readout duration, which reduces T2* relaxation losses and off-resonance effects, and to the linear geometry of phantoms and vessels, which can obscure centric blurring artifacts.

  • An in vivo model for functional MRI in cat visual cortex.

    8 August 2018

    A protocol is described for obtaining functional magnetic resonance images in anesthetized cat brain based on the blood oxygenation level dependent (BOLD) contrast mechanism. A visual stimulus was used, which consisted of a high-contrast drifting grating, whose speed and spatial frequency was optimized for cat area 18 (V2). Experiments were conducted at 4.7 Tesla using a gradient echo EPI sequence with a 29-ms echo time, yielding signal changes of between 0.7% and 2% in area 18.

  • Magnetic resonance imaging methods for study of human brain function and their application at high magnetic field.

    8 August 2018

    Magnetic resonance imaging (MRI) sequences are finding a new application in the study of human brain function by monitoring localized changes in signal intensity which accompany neuronal activity. These sequences can be sensitized to changes in cerebral blood volume, cerebral blood flow, and blood oxygenation, all of which reflect aspects of neuronal activity in the brain. Many of these experiments benefit from being implemented at a higher magnetic field strength than conventional MRI. An overview of these techniques is presented, and examples of their use are given.