3D X-ray Histology for the Investigation of Temporal Lobe Epilepsy in a Mouse Model.

The most common form of epilepsy among adults is mesial temporal lobe epilepsy (mTLE), with seizures often originating in the hippocampus due to abnormal electrical activity. The gold standard for the histopathological analysis of mTLE is histology, which is a two-dimensional technique. To fill this gap, we propose complementary three-dimensional (3D) X-ray histology. Herein, we used synchrotron radiation-based phase-contrast microtomography with 1.6 µm-wide voxels for the post mortem visualization of tissue microstructure in an intrahippocampal-kainate mouse model for mTLE. We demonstrated that the 3D X-ray histology of unstained, unsectioned, paraffin-embedded brain hemispheres can identify hippocampal sclerosis through the loss of pyramidal neurons in the first and third regions of the Cornu ammonis as well as granule cell dispersion within the dentate gyrus. Morphology and density changes during epileptogenesis were quantified by segmentations from a deep convolutional neural network. Compared to control mice, the total dentate gyrus volume doubled and the granular layer volume quadrupled 21 days after injecting kainate. Subsequent sectioning of the same mouse brains allowed for benchmarking 3D X-ray histology against well-established histochemical and immunofluorescence stainings. Thus, 3D X-ray histology is a complementary neuroimaging tool to unlock the third dimension for the cellular-resolution histopathological analysis of mTLE.

Comparing efficacy and side effects of two systemic chemotherapy regimens for eye-preserving therapy in children with retinoblastoma.

BACKGROUND: Eye-preserving therapy in retinoblastoma comprises systemic chemotherapy, but studies analyzing the efficacy of different chemotherapy regimens are scarce. METHODS: The efficacy and side effects of two different eye-preserving chemotherapy regimens containing either vincristine, etoposide, and carboplatin (VEC) or cyclophosphamide, vincristine, etoposide, and carboplatin (CyVEC) were compared in a prospective non-interventional observational study including children diagnosed with retinoblastoma between 2013 and 2019 in Germany and Austria. Event-free eye survival (EFES) and overall eye survival (OES) of all 164 eyes treated with both regimens and risk factors were investigated. RESULTS: The EFES after VEC (2-year EFES 72.3%) was higher than after CyVEC (2-year EFES 50.4%) (plogrank  < .001). The OES did not differ significantly between the two treatment groups (plogrank  = .77; 2-year OES VEC: 82.1% vs. CyVEC: 84.8%). Advanced International Classification of Retinoblastoma (ICRB) group was prognostic for a lower EFES (plogrank  < .0001; 2-year EFES ICRB A/B/C 71.3% vs. ICRB D/E 43.0%) and OES (plogrank  < .0001; 2-year OES ICRB A/B/C 93.1% vs. ICRB D/E 61.5%). The multivariate analysis showed that age at diagnosis older than 12 months and ICRB A/B/C were associated with better EFES. No second malignancies or ototoxicities were reported after a follow-up of median 3.1 years after diagnosis of retinoblastoma (range 0.1-6.9 years). CONCLUSIONS: Despite omitting cyclophosphamide, the EFES was higher after VEC chemotherapy that contains higher doses of carboplatin compared to CyVEC. The major risk factor for enucleation was advanced ICRB tumor grouping. Randomized clinical trials on efficacy and side effects of eye-preserving chemotherapy are required to tailor treatment protocols for retinoblastoma patients.

Shedding Light on Metal-Based Nanoparticles in Zebrafish by Computed Tomography with Micrometer Resolution.

Metal-based nanoparticles are clinically used for diagnostic and therapeutic applications. After parenteral administration, they will distribute throughout different organs. Quantification of their distribution within tissues in the 3D space, however, remains a challenge owing to the small particle diameter. In this study, synchrotron radiation-based hard X-ray tomography (SRµCT) in absorption and phase contrast modes is evaluated for the localization of superparamagnetic iron oxide nanoparticles (SPIONs) in soft tissues based on their electron density and X-ray attenuation. Biodistribution of SPIONs is studied using zebrafish embryos as a vertebrate screening model. This label-free approach gives rise to an isotropic, 3D, direct space visualization of the entire 2.5 mm-long animal with a spatial resolution of around 2 µm. High resolution image stacks are available on a dedicated internet page (http://zebrafish.pharma-te.ch). X-ray tomography is combined with physico-chemical characterization and cellular uptake studies to confirm the safety and effectiveness of protective SPION coatings. It is demonstrated that SRµCT provides unprecedented insights into the zebrafish embryo anatomy and tissue distribution of label-free metal oxide nanoparticles.

Simultaneous Three-Dimensional Vascular and Tubular Imaging of Whole Mouse Kidneys With X-ray µCT.

Concurrent three-dimensional imaging of the renal vascular and tubular systems on the whole-kidney scale with capillary level resolution is labor-intensive and technically difficult. Approaches based on vascular corrosion casting and X-ray micro computed tomography (µCT), for example, suffer from vascular filling artifacts and necessitate imaging with an additional modality to acquire tubules. In this work, we report on a new sample preparation, image acquisition, and quantification protocol for simultaneous vascular and tubular µCT imaging of whole, uncorroded mouse kidneys. The protocol consists of vascular perfusion with the water-soluble, aldehyde-fixable, polymeric X-ray contrast agent XlinCA, followed by laboratory-source µCT imaging and structural analysis using the freely available Fiji/ImageJ software. We achieved consistent filling of the entire capillary bed and staining of the tubules in the cortex and outer medulla. After imaging at isotropic voxel sizes of 3.3 and 4.4 µm, we segmented vascular and tubular systems and quantified luminal volumes, surface areas, diffusion distances, and vessel path lengths. This protocol permits the analysis of vascular and tubular parameters with higher reliability than vascular corrosion casting, less labor than serial sectioning and leaves tissue intact for subsequent histological examination with light and electron microscopy.

Rupture of the Globe: What to Do, What not to Do. / Bulbusberstung: Vorgehen und Ergebnisse.

Due to their complexity, globe ruptures are highly compromising traumas for the patient. This is due on the one hand to the eye injury itself with the accompanying loss of vision and on the other hand due to the need for extended treatment with uncertain prognosis and the resulting psychological stress. Globe ruptures are among the prognostically most unfavorable injuries due to the force and peak pressure impacting the eye. Furthermore, contusional retinal necrosis may be of significance prognostically. In the present review, we discuss treatment of globe ruptures involving retinal surgery. We discuss the primary sugery, its chronological planning and extent as well as the necessity for follow-up interventions. We also discuss the origin of traumatic retinal detachment with differential diagnosis of giant retinal tear versus oradialysis as well as secondary sequelae of traumas such as formation of macular holes and their treatment. On this basis, the use of buckling surgery versus pars-plana vitrectomy is discussed. Further focus is set on the role of the iris lens diaphragm in surgery of globe ruptures.

Small-Angle Neutron Scattering Study of Temperature-Induced Structural Changes in Liposomes.

Liposomes of specific artificial phospholipids, such as Pad-PC-Pad and Rad-PC-Rad, are mechanically responsive. They can release encapsulated therapeutics via physical stimuli, as naturally present in blood flow of constricted vessel segments. The question is how these synthetic liposomes change their structure in the medically relevant temperature range from 22 to 42 °C. In the present study, small-angle neutron scattering (SANS) was employed to evaluate the temperature-induced structural changes of selected artificial liposomes. For Rad-PC-Rad, Pad-Pad-PC, Sur-PC-Sur, and Sad-PC-Sad liposomes, the SANS data have remained constant because the phase transition temperatures are above 42 °C. For Pad-PC-Pad and Pes-PC-Pes liposomes, whose phase transitions are below 42 °C, the q-plots have revealed temperature-dependent structural changes. The average diameter of Pad-PC-Pad liposomes remained almost constant, whereas the eccentricity decreased by an order of magnitude. Related measurements using transmission electron microscopy at cryogenic temperatures, as well as dynamic light scattering before and after the heating cycles, underpin the fact that the non-spherical liposomes flatten out. The SANS data further indicated that, as a consequence of the thermal loop, the mean bilayer thickness increased by 20%, associated with the loss of lipid membrane interdigitation. Therefore, Pad-PC-Pad liposomes are unsuitable for local drug delivery in the atherosclerotic human blood vessel system. In contrast, Rad-PC-Rad liposomes are thermally stable for applications within the human body.

Navigated laser photocoagulation in patients with non-resolving and chronic central serous chorioretinopathy.

PURPOSE: To evaluate the efficacy of navigated focal laser photocoagulation in patients with chronic central serous chorioretinopathy (CSCR) and active leakage on fluorescein angiography (FA). METHODS: Thirty-two eyes of 32 patients (age 48 ± 11, m/f = 24/8) with persistent or recurrent CSCR (> 3 months) who received navigated laser photocoagulation (Navilas®) of leaking point(s) between June 2013 and 2016 were included in this retrospective case series. Outcome parameters after 4 weeks and 3 months were the number of patients presenting with complete resolution of subretinal fluid, the volume of subretinal fluid measured on SD-OCT (Spectralis Heidelberg Engineering©), and best corrected visual acuity (BCVA/ (Snellen equivalent). RESULTS: Complete resolution of subretinal fluid was achieved in 17 eyes (50%) after 4 weeks and in 24 eyes (75%) after 3 months with an average number of 1.3 laser procedures (range 1-3). Five eyes displayed a nearly complete resolution with a reduction of over 80% of the subretinal fluid compared to baseline. Three eyes showed no reduction in subretinal fluid. BCVA improved from median 0.58 (range 0.16-1.25) to 0.66 (0.16-1.0) (p = 0.001). The seven patients who had been treated within the central 1 mm of the ETDRS-OCT Grid but outside the avascular foveal zone showed an improvement of BCVA from median 0.6 (range 0.2-1.0) to 0.8 (0.2-1.0). No patient experienced a treatment-induced visual loss. CONCLUSIONS: Laser treatment with Navilas® using eye tracking and FA-based planning is a safe and effective alternative therapy in patients with chronic CSCR.

[Ultra-Wide Field Retinal Imaging and Angiography in the Differential Diagnosis and Therapeutic Decisions in Vascular Diseases of the Peripheral Retina]. / Ultraweitwinkel-Fundusfotografie und -angiografie in der Differenzialdiagnose und zur Therapieplanung bei peripheren vaskulären Netzhauterkrankungen.

Investigation of vascular diseases of the peripheral retina requires imaging procedures that allow a comprehensive view of the periphery, as well as reproducible pictures. In particular, ultra-wide field fluorescence angiography facilitates diagnosis, therapeutic decisions and follow-up examinations. While vasculopathies such as Coats disease and familiar exudative vitreoretinopathy are diagnosed within the first and second decade of life, patients' compliance during fundus imaging is typically reduced within this age range. Compared to the repeated imaging procedures for composite formation, ultra-wide field imaging has significantly reduced recording time. Nevertheless, current imaging systems are not able to map the entire retina in scaled proportions. Therefore, the imaging frame must be guided by patients' gaze onto the affected retinal area. Moreover, the medical photographer must be aware of the clinical setting and the region of interest. Hence, previous detailed funduscopy by trained ophthalmologists will remain indispensable.

Prenatal growth stages show the development of the ruminant bony labyrinth and petrosal bone.

Foetuses are a source of scientific information to understand the development and evolution of anatomical structures. The bony labyrinth, surrounding the organ of balance and hearing, is a phylogenetically and ecologically informative structure for which still little concerning growth and shape variability is known in many groups of vertebrates. Except in humans, it is poorly known in many other placentals and its prenatal growth has almost never been studied. Ruminants are a diversified group of placentals and represent an interesting case study to understand the prenatal growth of the ear region. We computed tomography -scanned five cow foetuses and an adult petrosal bone (Bos taurus, Artiodactyla, Mammalia), and describe the bony labyrinth when already ossified. The foetuses encompass the second half of the 9.3-month-long gestation period of the cow. They were sampled at different ontogenetic stages to understand how and when the petrosal bone and bony labyrinth ossify in ruminants. The petrosal bone and bony labyrinth ossify within about 20 days in the fourth month of gestation. The bony labyrinth is already fully ossified at least in the 6th month, while only the cochlea, most of the vestibule and the common crus are already ossified at the beginning of the 4th month. The pars canalicularis of the petrosal thus ossifies at last. The size and volume of the bony labyrinth stay similar from the 6th month (possibly even from the 5th). From the end of the 4th month of gestation, a progressive lengthening of the cochlear aqueduct and endolymphatic sac occurs, culminating in the adult form and partly explaining the larger volume of the later. The inner ear in the cow ossifies quickly during the gestation period, being fully ossified around mid-gestation time, as in humans. The adult size and most of its volume are reached by mid-gestation time while the petrosal bone and skull still grow. A negative ontogenetic allometry between the bony labyrinth and the petrosal bone and skull is thus observed. It matches the evolutionary negative allometry of the structure observed in earlier studies. Few changes occur after ossification is achieved; only open structures (i.e. cochlear aqueduct and endolymphatic sac) continue to grow after birth and reflect size increase of the petrosal bone.

Extending two-dimensional histology into the third dimension through conventional micro computed tomography.

Histological examination achieves sub-micrometer resolution laterally. In the third dimension, however, resolution is limited to section thickness. In addition, histological sectioning and mounting sections on glass slides introduce tissue-dependent stress and strain. In contrast, state-of-the-art hard X-ray micro computed tomography (µCT) systems provide isotropic sub-micrometer resolution and avoid sectioning artefacts. The drawback of µCT in the absorption contrast mode for visualising physically soft tissue is a low attenuation difference between anatomical features. In this communication, we demonstrate that formalin-fixed paraffin-embedded human cerebellum yields appropriate absorption contrast in laboratory-based µCT data, comparable to conventional histological sections. Purkinje cells, for example, are readily visible. In order to investigate the pros and cons of complementary approaches, two- and three-dimensional data were manually and automatically registered. The joint histogram of histology and the related µCT slice allows for a detailed discussion on how to integrate two-dimensional information from histology into a three-dimensional tomography dataset. This methodology is not only rewarding for the analysis of the human cerebellum, but it also has relevance for investigations of tissue biopsies and post-mortem applications. Our data indicate that laboratory-based µCT as a modality can fill the gap between synchrotron radiation-based µCT and histology for a variety of tissues. As the information from haematoxylin and eosin (H&E) stained sections and µCT data is related, one can colourise local X-ray absorption values according to the H&E stain. Hence, µCT data can correlate and virtually extend two-dimensional (2D) histology data into the third dimension.

Thin Film Formation and Morphology of Electrosprayed Polydimethylsiloxane.

Low-voltage dielectric actuators (DEAs) can be fabricated using submicrometer-thin polydimethylsiloxane (PDMS) films. The two established techniques, namely spin coating and molecular beam deposition, however, are inappropriate to produce multistack DEAs in an efficient way. Therefore, we propose an alternative deposition technique, i.e., the alternating current electrospray deposition (ACESD) of 5 vol % PDMS in ethyl acetate solution and subsequent ultraviolet light curing. Atomic force microscopy makes possible the three-dimensional analysis of cured droplet-like islands. These circular islands, prepared on 2 in. Si(100) wafers from four polymers with molecular masses between 800 and 62,700 g/mol, reveal a characteristic morphology with an increasing height-to-diameter ratio. Using the 6000 g/mol polymer for ACESD, the film morphology evolution was tracked by applying conventional optical microscopy and spectroscopic ellipsometry. When the deposition was terminated after 13 s, circular islands with a mean height of 30 nm were found, while terminating the deposition after about 155 s led to a confluent layer with a mean height of 91 ± 10 nm. Potential electrostatic interactions between the droplets could not be identified through the analysis of spatial island distribution. Nevertheless, ACESD is a budget-priced and competitive deposition technique that can be employed to fabricate submicrometer-thin PDMS films with true nanometer roughness.

Surprising lack of liposome-induced complement activation by artificial 1,3-diamidophospholipids in vitro.

Cardio-vascular diseases are the main cause of death, emphasizing the need to improve patient treatment and survival. One therapeutic approach is a liposome-based drug carrier system specifically targeting constricted arteries. The recently discovered mechano-sensitive liposomes use hemodynamic shear-stress differences between healthy and constricted blood vessels as trigger for drug release. Liposomes are promising delivery containers but are being recognized as foreign by the immune system. Complement activation as essential factor of the recognition leads to adverse effects. Here, we tested complement activation by liposomes formulated from the artificial phospholipid Pad-PC-Pad in vitro. Surprisingly no complement activation was detected in human sera and porcine plasma. In in vivo experiments with three pigs, neither anaphylactic reactions nor other significant hemodynamic changes were observed even at comparably high liposome doses. The pilot study holds promise for an absence of complement-mediated adverse effects of Pad-PC-Pad liposomes in human. FROM THE CLINICAL EDITOR: A lot of research has been done on new treatment for cardiovascular diseases. Liposome-based carrier systems have also shown promises. In this article, the authors studied the potential risks of complement activation by liposomes in in-vivo experiments. The absence of complement activation by Pad-PC-Pad liposomes may indicate its use in humans.

Monthly microperimetry (MP1) measurement of macular sensitivity after dexamethasone implantation (Ozurdex) in retinal vein occlusions.

PURPOSE: To evaluate changes in macular sensitivity as measured via microperimetry (MP) in patients with macular edema (ME) secondary to retinal vein occlusion (RVO) after dexamethasone implantation (DEX implantation, Ozurdex), in comparison to distance visual acuity, reading ability, and spectral domain optical coherence tomography (SD-OCT). METHODS: Twenty-three patients with ME secondary to RVO were treated with a DEX implantation in this prospective, observational case study. Patients were controlled at baseline and then monthly with microperimetry and assessment of distance visual acuity, reading ability, and SD- OCT. Side effects of the DEX implant were monitored by measuring the intraocular pressure (IOP) and lens grading with Lens Opacities Classification System (LOCS) charts. RESULTS: The 23 patients with RVO included 16 patients with branch retinal vein occlusion (BRVO) and 7 patients with central retinal vein occlusion (CRVO). Improvement in distance visual acuity, reading ability, and in central 8-points microperimetry showed statistical significance from month 1 to 3, whereas the 40-points microperimetry improved with statistical significance from month 1 to 2. The reduction of central retinal thickness measured with SD-OCT remained statistically significant until month 4. Subgroup analysis of patients with BRVO and CRVO confirmed the best test results observed at month two after DEX implantation. CONCLUSIONS: The highest macular sensitivity was measured two months after DEX implantation. This corresponds to the best test results for distance visual acuity, reading ability, and SD-OCT observed two months after treatment.

Clinical outcomes after switching treatment from intravitreal ranibizumab to aflibercept in neovascular age-related macular degeneration.

PURPOSE: To describe the treatment response to aflibercept in patients with exudative age-related macular degeneration that showed insufficient or diminishing treatment effects under ranibizumab. METHODS: From December 2012 till June 2013 all patients receiving intravitreal injections of aflibercept after previous treatment with ranibizumab were collected in a database and retrospectively reviewed. Clinical data such as visual acuity or central subfield retinal thickness on optical coherence tomography (OCT) scans were analyzed for the time frame before, during, and shortly after the aflibercept injections. Of particular interest was the comparison of clinical features under ongoing ranibizumab treatment to the time during aflibercept treatment. RESULTS: Seventy-one eyes of 65 patients were included in the study. All eyes had previous ranibizumab injections in their medical history, the average number of which was nine (range 3-43). For the total group the mean visual acuity (VA) before the first ranibizumab injection was 0.54 logMAR, and after the last ranibizumab injection was 0.57 logMAR. Mean VA changed from 0.47 logMAR before the first aflibercept injection to 0.25 logMAR after the last aflibercept injection. Central subfield retinal thickness (CSRT) on OCT changed from a mean of 417.28 µm to 349.52 µm under ranibizumab treatment and from 338.76 µm to 272.00 µm under aflibercept treatment. Interestingly, 33 % of cases that did not show a functional improvement under ranibizumab therapy gained visual acuity after aflibercept treatment. CONCLUSION: Aflibercept appears to be an effective choice for patients with neovascular age-related macular degeneration who were resistant to previous therapy of ranibizumab. The longevity of this effect still remains questionable.

Differentiation of human mesenchymal stem cells on plasma-treated polyetheretherketone.

Polyetheretherketone (PEEK) generally exhibits physical and chemical characteristics that prevent osseointegration. To activate the PEEK surface, we applied oxygen and ammonia plasma treatments. These treatments resulted in surface modifications, leading to changes in nanostructure, contact angle, electrochemical properties and protein adhesion in a plasma power and process gas dependent way. To evaluate the effect of the plasma-induced PEEK modifications on stem cell adhesion and differentiation, adipose tissue-derived mesenchymal stem cells (adMSC) were seeded on PEEK specimens. We demonstrated an increased adhesion, proliferation, and osteogenic differentiation of adMSC in contact to plasma-treated PEEK. In dependency on the process gas (oxygen or ammonia) and plasma power (between 10 and 200 W for 5 min), varying degrees of osteogenic differentiation were induced. When adMSC were grown on 10 and 50 W oxygen and ammonia plasma-treated PEEK substrates they exhibited a doubled mineralization degree relative to the original PEEK. Thus plasma treatment of PEEK specimens induced changes in surface chemistry and topography and supported osteogenic differentiation of adMSC in vitro. Therefore plasma treated PEEK holds perspective for contributing to osseointegration of dental and orthopedic load-bearing PEEK implants in vivo.

Retinal blood flow velocities in infants with retinopathy of prematurity after intravitreal administration of bevacizumab.

BACKGROUND/OBJECTIVES: Progression of retinopathy of prematurity (ROP) is associated with increased retinal blood flow velocities. We investigated changes of central retinal arterial and venous blood flow after intravitreal administration of bevacizumab. SUBJECTS/METHODS: Prospective observational study using serial ultrasound Doppler imaging in preterm infants with bevacizumab-treated ROP. Eyes were examined 1 [0-2] days before injection (median [interquartile range]), and at three time points after injection (1 [1-2] days, 6 [3-8] days, and 17 [9-28] days). Preterm infants with ROP stage 2 displaying spontaneous regression served as controls. RESULTS: In 21 eyes of 12 infants with bevacizumab-treated ROP, peak arterial systolic velocity declined from 13.6 [11.0-16.3] cm/s prior to intravitreal bevacizumab to 11.2 [9.4-13.9] cm/s, 10.6 [9.2-13.3] cm/s and 9.3 [8.2-11.0] cm/s at discharge (p = .002). There was also a decline of the arterial velocity time integral (from 3.1 [2.3-3.9] cm to 2.9 [2.4-3.5], 2.7 [2.3-3.2] cm and 2.2 [2.0-2.7], p = .021) and mean velocity in the central retinal vein (from 4.5 [3.6-5.8] cm/s to 3.7 [2.6-4.1] cm/s, 3.5 [3.0-4.3] cm/s, and 3.2 [2.8-4.6] cm/s, p = .012). Arterial end-diastolic velocity and resistance index remained unchanged. Blood flow velocities in bevacizumab-treated eyes examined before injection were significantly higher than those measured in untreated eyes that ultimately showed spontaneous regression of ROP. Sequential examinations in these controls did not reveal any declines of retinal blood flow velocities. CONCLUSION: Increased retinal arterial and venous blood flow velocities in infants with threshold ROP decline following intravitreal bevacizumab injection.

Multi-resolution X-ray phase-contrast and dark-field tomography of human cerebellum with near-field speckles.

In this study, we use synchrotron-based multi-modal X-ray tomography to examine human cerebellar tissue in three dimensions at two levels of spatial resolution (2.3 µm and 11.9 µm). We show that speckle-based imaging (SBI) produces results that are comparable to propagation-based imaging (PBI), a well-established phase-sensitive imaging method. The different SBI signals provide complementary information, which improves tissue differentiation. In particular, the dark-field signal aids in distinguishing tissues with similar average electron density but different microstructural variations. The setup's high resolution and the imaging technique's excellent phase sensitivity enabled the identification of different cellular layers and additionally, different cell types within these layers. We also correlated this high-resolution phase-contrast information with measured dark-field signal levels. These findings demonstrate the viability of SBI and the potential benefit of the dark-field modality for virtual histology of brain tissue.

Fluocinolone Acetonide Implant for Uveitis: Dissecting Responder and Non-Responder Outcomes at a Tertiary Center.

Macular edema (ME) remains a primary cause of visual deterioration in uveitis. Visual acuity (VA) can often be maintained using corticosteroid depot systems. This study evaluated the efficacy of a fluocinolone acetonide (FAc) intravitreal implant (ILUVIEN®) in treating non-infectious uveitis using real-world data. This retrospective analysis included 135 eyes subdivided into responders and non-responders. Central retinal thickness (CRT), VA, and intraocular pressure (IOP) were followed over time. A significant decrease in CRT and an increase in VA were observed in all eyes throughout the follow-up period (p < 0.01). An IOP increase (p = 0.028) necessitated treatment in 43% of eyes by Month 6. Non-responders were older (p = 0.004) and had been treated with more dexamethasone (DEX) implants (p = 0.04); 89.3% had a defect in the external limiting membrane (ELM) and inner/outer segment (IS/OS) zone (p < 0.001). Immunomodulatory therapy had no impact on treatment response. Pars plana vitrectomy (PPV) patients had a mean CRT reduction of 47.55 µm and a reduced effect by Month 24 (p = 0.046) versus non-PPV patients. We conclude that the FAc implant achieves long-term control of CRT and improves VA. Increases in IOP were manageable. Eyes with a previous PPV showed milder results. Data showed a correlation between older age, a damaged ELM and IS/OS zone, frequent DEX inserts, and poorer outcome measures.

Terabyte-scale supervised 3D training and benchmarking dataset of the mouse kidney.

The performance of machine learning algorithms, when used for segmenting 3D biomedical images, does not reach the level expected based on results achieved with 2D photos. This may be explained by the comparative lack of high-volume, high-quality training datasets, which require state-of-the-art imaging facilities, domain experts for annotation and large computational and personal resources. The HR-Kidney dataset presented in this work bridges this gap by providing 1.7 TB of artefact-corrected synchrotron radiation-based X-ray phase-contrast microtomography images of whole mouse kidneys and validated segmentations of 33 729 glomeruli, which corresponds to a one to two orders of magnitude increase over currently available biomedical datasets. The image sets also contain the underlying raw data, threshold- and morphology-based semi-automatic segmentations of renal vasculature and uriniferous tubules, as well as true 3D manual annotations. We therewith provide a broad basis for the scientific community to build upon and expand in the fields of image processing, data augmentation and machine learning, in particular unsupervised and semi-supervised learning investigations, as well as transfer learning and generative adversarial networks.

Apochromatic X-ray focusing.

Achromatic doublets are combinations of two individual lenses designed to focus different wavelengths of light in the same position. Apochromatic optics are improved versions of the achromatic schemes which extend the wavelength range significantly. Both achromatic and apochromatic optics are well-established for visible light. However, X-ray achromatic lenses did not exist until very recently, and X-ray apochromatic lenses have never been experimentally demonstrated. Here, we create an X-ray apochromatic lens system using an appropriate combination of a Fresnel zone plate and a diverging compound refractive lens with a tuned separation distance. The energy-dependent performance of this apochromat was characterized at photon energies between 6.5 and 13.0 keV by ptychographic reconstruction of the focal spot and scanning transmission X-ray microscopy of a resolution test sample. The apochromat delivered a reconstructed focal spot size of 940 × 740 nm2. The apochromatic combination shows a four-fold improvement in the chromatic aberration correction range compared to an achromatic doublet configuration. Thus, apochromatic X-ray optics have the potential to increase the focal spot intensity for a wide variety of X-ray applications.