The impact of acute nutritional interventions on the plasma proteome

Context: Humans respond profoundly to changes in diet, while nutrition and environment have a great impact on population health. It is therefore important to deeply characterize the human nutritional responses. Objective: Endocrine parameters and the metabolome of human plasma are rapidly responding to acute nutritional interventions such as caloric restriction or a glucose challenge. It is less well understood whether the plasma proteome would be equally dynamic, and whether it could be a source of corresponding biomarkers. Methods: We used high-throughput mass spectrometry to determine changes in the plasma proteome of i) 10 healthy, young, male individuals in response to 2 days of acute caloric restriction followed by refeeding; ii) 200 individuals of the Ely epidemiological study before and after a glucose tolerance test at 4 time points (0, 30, 60, 120 minutes); and iii) 200 random individuals from the Generation Scotland study. We compared the proteomic changes detected with metabolome data and endocrine parameters. Results: Both caloric restriction and the glucose challenge substantially impacted the plasma proteome. Proteins responded across individuals or in an individual-specific manner. We identified nutrient-responsive plasma proteins that correlate with changes in the metabolome, as well as with endocrine parameters. In particular, our study highlights the role of apolipoprotein C1 (APOC1), a small, understudied apolipoprotein that was affected by caloric restriction and dominated the response to glucose consumption and differed in abundance between individuals with and without type 2 diabetes. Conclusion: Our study identifies APOC1 as a dominant nutritional responder in humans and highlights the interdependency of acute nutritional response proteins and the endocrine system

Light-induced changes of the subretinal space of the temporal retina observed via optical coherence tomography

Photoreceptor function is impaired in many retinal diseases like age-related macular degeneration. Currently, assessment of the photoreceptor function for the early diagnosis and monitoring of these diseases is either subjective, as in visual field testing, requires contact with the eye, like in electroretinography, or relies on research prototypes with acquisition speeds unattained by conventional imaging systems. We developed an objective, noncontact method to monitor photoreceptor function using a standard optical coherence tomography system. This method can be used with various white light sources for stimulation. The technique was applied in five volunteers and detected a decrease of volume of the subretinal space associated with light adaptation processes of the retina.Published versio

Cutaneous optical coherence tomography for longitudinal volumetric assessment of intradermal volumes in a mouse model

Clinical evaluation of skin lesions requires precise and reproducible technologies for their qualitative and quantitative assessment. In this study, we investigate the applicability of a custom-built dermatologic OCT system for longitudinal assessment of intradermal volumes in a mouse model. The OCT, based on an akinetic swept laser working at 1310 nm was employed for visualization and quantification of intradermal deposits of three different hyaluronic acid-based hydrogel formulations – one commercial and two test substances. Hydrogels were applied in 22 BALB/c mice, and measurements were performed over a six-month time period. All hydrogels increased in volume within the first weeks and degraded steadily thereafter. The half-lifes of the test hydrogels (27.2 ± 13.6 weeks for Hydrogel 1, 31.5 ± 17.2 weeks for Hydrogel 2) were higher in comparison to the commercially available HA hydrogel (21.4 ± 12.0 weeks), although differences were not significant. The sphericity parameter was used for evaluation of the deposit geometry. While on the injection day the sphericities were similar (~0.75 ± 0.04), at later time points significant differences between the different test substances were found (T24: PRV 0.59 ± 0.09, Hydrogel 1 0.70 ± 0.11, Hydrogel 2 0.78 ± 0.07; p ≤ 0.012 for all pairs). This study shows the applicability of OCT imaging for quantitative assessment of the volumetric behavior of intradermal deposits in vivo.Published versio

Comparison of optical coherence tomography and high frequency ultrasound imaging in mice for the assessment of skin morphology and intradermal volumes

Optical coherence tomography (OCT) and high-frequency ultrasound (HFUS), two established imaging modalities in the field of dermatology, were evaluated and compared regarding their applicability for visualization of skin tissue morphology and quantification of murine intradermal structures. The accuracy and reproducibility of both methods were assessed ex vivo and in vivo using a standardized model for intradermal volumes based on injected soft tissue fillers. OCT revealed greater detail in skin morphology, allowing for detection of single layers due to the superior resolution. Volumetric data measured by OCT (7.9 ± 0.3 μl) and HFUS (7.7 ± 0.5 μl) were in good agreement and revealed a high accuracy when compared to the injected volume of 7.98 ± 0.8 µl. In vivo, OCT provided a higher precision (relative SD: 26% OCT vs. 42% HFUS) for the quantification of intradermal structures, whereas HFUS offered increased penetration depth enabling the visualization of deeper structures. A combination of both imaging technologies might be valuable for tumor assessments or other dermal pathologies in clinical settings.Published versio

Automatic assessment of tear film and tear meniscus parameters in healthy subjects using ultrahigh-resolution optical coherence tomography

Many different parameters exist for the investigation of tear film dynamics. We present a new tear meniscus segmentation algorithm which automatically extracts tear meniscus area (TMA), height (TMH), depth (TMD) and radius (TMR) from UHR-OCT measurements and apply it to a data set including repeated measurements from ten healthy subjects. Mean values and standard deviations are 0.0174 ± 0.007 mm2, 0.272 ± 0.069 mm, 0.191 ± 0.049 mm and 0.309 ± 0.123 mm for TMA, TMH, TMD and TMR, respectively. A significant correlation was found between all respective tear meniscus parameter pairs (all p < 0.001, all Pearson’s r ≥ 0.657). Challenges, limitations and potential improvements related to the data acquisition and the algorithm itself are discussed. The automatic segmentation of tear meniscus measurements acquired with UHR-OCT might help in a clinical setting to further understand the tear film and related medical conditions like dry eye disease.Published versio

Quantification of intrinsic optical signals in the outer human retina using optical coherence tomography

Intrinsic optical signals constitute a noninvasive biomarker promising the objective assessment of retinal photoreceptor function. We employed a commercial optical coherence tomography (OCT) system and an OCT signal model for evaluation of optical path length (OPL) changes in the temporal outer retina of five healthy subjects during light adaptation. Data were acquired at 30 time points, in ambient light and during long duration stimulation with white light, and analyzed, employing a signal model based on the sum of seven Gaussian curves corresponding to all relevant anatomical structures of the outer retina. During light stimulation, mean OPL between rod outer segment tips (ROST) and the retinal pigment epithelium (RPE) decreased by 21.4 ± 3.5%. Further, OPL between the external-limiting membrane (ELM) and the RPE decreased by 5.2 ± 0.9% versus baseline, while OPL between ELM and ROST showed an initial decrease by 2.1 ± 1.6% versus baseline and, thereafter, increased by 2.8 ± 2.1% versus baseline. Thus, the presented approach allowed for assess to dynamic changes in the outer retina in response to light. The change in the subretinal space occurring in the context of light adaptation could be measured using a standard OCT platform and a dedicated signal model.Published versionThe research has been funded by the Vienna Science and Technology Fund (WWTF) through project LS14-067

CorneaNet : fast segmentation of cornea OCT scans of healthy and keratoconic eyes using deep learning

Deep learning has dramatically improved object recognition, speech recognition, medical image analysis and many other fields. Optical coherence tomography (OCT) has become a standard of care imaging modality for ophthalmology. We asked whether deep learning could be used to segment cornea OCT images. Using a custom-built ultrahigh-resolution OCT system, we scanned 72 healthy eyes and 70 keratoconic eyes. In total, 20,160 images were labeled and used for the training in a supervised learning approach. A custom neural network architecture called CorneaNet was designed and trained. Our results show that CorneaNet is able to segment both healthy and keratoconus images with high accuracy (validation accuracy: 99.56%). Thickness maps of the three main corneal layers (epithelium, Bowman’s layer and stroma) were generated both in healthy subjects and subjects suffering from keratoconus. CorneaNet is more than 50 times faster than our previous algorithm. Our results show that deep learning algorithm scan be used for OCT image segmentation and could be applied in various clinical settings. In particular, CorneaNet could be used for early detection of keratoconus and more generally to study other diseases altering corneal morphology.Published versio

European Spine Journal / Does T2 mapping of the posterior annulus fibrosus indicate the presence of lumbar intervertebral disc herniation? : A 3.0 Tesla magnetic resonance study

Purpose Indicating lumbar disc herniation via magnetic resonance imaging (MRI) T2 mapping in the posterior annulus fibrosus (AF). Methods Sagittal T2 maps of 313 lumbar discs of 64 patients with low back pain were acquired at 3.0 Tesla (3T). The discs were rated according to disc herniation and bulging. Region of interest (ROI) analysis was performed on median, sagittal T2 maps. T2 values of the AF, in the most posterior 10% (PAF-10) and 20% of the disc (PAF-20), were compared. Results A significant increase in the T2 values of discs with herniations affecting the imaged area, compared to bulging discs and discs with lateral herniation, was shown in the PAF-10, where no association to the NP was apparent. The PAF-20 exhibited a moderate correlation to the nucleus pulposus (NP). Conclusions High T2 values in the PAF-10 suggest the presence of disc herniation (DH). The results indicate that T2 values in the PAF-20 correspond more to changes in the NP.(VLID)352441

Automated segmentation of dermal fillers in OCT images of mice using convolutional neural networks

We present a system for automatic determination of the intradermal volume of hydrogels based on optical coherence tomography (OCT) and deep learning. Volumetric image data was acquired using a custom-built OCT prototype that employs an akinetic swept laser at ~1310 nm with a bandwidth of 87 nm, providing an axial resolution of ~6.5 μm in tissue. Three-dimensional data sets of a 10×10 mm skin patch comprising the intradermal filler and the surrounding tissue were acquired. A convolutional neural network using a u-net-like architecture was trained from slices of 100 OCT volume data sets where the dermal filler volume was manually annotated. Using six-fold cross-validation, a mean accuracy of 0.9938 and a Jaccard similarity coefficient of 0.879 were achieved.Published versio

Sodium MR imaging of the lumbar intervertebral disk at 7 T: correlation with T2 mapping and modified Pfirrmann score at 3 T - preliminary results

PURPOSE: To compare sodium imaging of lumbar intervertebral disks in asymptomatic volunteers at 7-T magnetic resonance (MR) imaging with quantitative T2 mapping and morphologic scoring at 3 T. MATERIALS AND METHODS: Following ethical board approval and informed consent, the L2-3 to L5-S1 disks were examined in 10 asymptomatic volunteers (nine men, one woman; mean age, 30 years; range, 23-43 years). At 7 T, normalized sodium signal-to-noise ratios were calculated, by using region-of-interest analysis. At 3 T, T2 mapping was performed with a multiecho spin-echo sequence (repetition time msec/echo times msec, 1500/24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156). T2 values were calculated over the nucleus, with a pixelwise, monoexponential nonnegative least-squares-fit analysis. Morphologic grading according to a modified Pfirrmann score was assessed independently by three experienced musculoskeletal radiologists, and Pearson correlation analysis of the covariates was performed. RESULTS: The mean normalized sodium signal intensity was 275.5±115.4 (standard deviation). The T2 mapping showed a mean value of 89.8 msec±19.34. The median modified Pfirrmann score was 2b (90% had score≤3c). The Pearson correlation coefficient showed a cubic function between sodium imaging and the modified Pfirrmann score, a moderate inverse correlation between T2 mapping and the modified Pfirrmann score (r=-0.62), and no correlation between sodium imaging and T2 mapping (r=0.06). CONCLUSION: The results suggest that MR imaging of the intervertebral disk, using sodium imaging and T2 mapping, can help characterize different component changes and that both of these methods are to some degree related to the Pfirrmann score