Semantic segmentation of non-linear multimodal images for disease grading of inflammatory bowel disease: A segnet-based application

Non-linear multimodal imaging, the combination of coherent anti-stokes Raman scattering (CARS), two-photon excited fluorescence (TPEF) and second harmonic generation (SHG), has shown its potential to assist the diagnosis of different inflammatory bowel diseases (IBDs). This label-free imaging technique can support the ‘gold-standard’ techniques such as colonoscopy and histopathology to ensure an IBD diagnosis in clinical environment. Moreover, non-linear multimodal imaging can measure biomolecular changes in different tissue regions such as crypt and mucosa region, which serve as a predictive marker for IBD severity. To achieve a real-time assessment of IBD severity, an automatic segmentation of the crypt and mucosa regions is needed. In this paper, we semantically segment the crypt and mucosa region using a deep neural network. We utilized the SegNet architecture (Badrinarayanan et al., 2015) and compared its results with a classical machine learning approach. Our trained SegNet mod el achieved an overall F1 score of 0.75. This model outperformed the classical machine learning approach for the segmentation of the crypt and mucosa region in our study

Computational tissue staining of non-linear multimodal imaging using supervised and unsupervised deep learning

Hematoxylin and Eosin (H&E) staining is the 'gold-standard' method in histopathology. However, standard H&E staining of high-quality tissue sections requires long sample preparation times including sample embedding, which restricts its application for 'real-time' disease diagnosis. Due to this reason, a label-free alternative technique like non-linear multimodal (NLM) imaging, which is the combination of three non-linear optical modalities including coherent anti-Stokes Raman scattering, two-photon excitation fluorescence and second-harmonic generation, is proposed in this work. To correlate the information of the NLM images with H&E images, this work proposes computational staining of NLM images using deep learning models in a supervised and an unsupervised approach. In the supervised and the unsupervised approach, conditional generative adversarial networks (CGANs) and cycle conditional generative adversarial networks (cycle CGANs) are used, respectively. Both CGAN and cycle CGAN models generate pseudo H&E images, which are quantitatively analyzed based on mean squared error, structure similarity index and color shading similarity index. The mean of the three metrics calculated for the computationally generated H&E images indicate significant performance. Thus, utilizing CGAN and cycle CGAN models for computational staining is beneficial for diagnostic applications without performing a laboratory-based staining procedure. To the author's best knowledge, it is the first time that NLM images are computationally stained to H&E images using GANs in an unsupervised manner

Apolipoprotein D concentration in human plasma during aging and in Parkinson\u2019s Disease: a cross-sectional study

Apolipoprotein D (ApoD), a lipocalin transporter of small hydrophobic molecules, plays an important role in several neurodegenerative diseases. ApoD is expressed in and secreted from a variety of peripheral and brain tissues. Increments of ApoD have been reported in relation with oxidative stress conditions, aging, and degeneration in the nervous system. Preliminary findings support the role of ApoD in neuroprotection. However, its role in PD remains unclear. To date, no studies have been performed on the relationship between ApoD in the blood and PD, as neurodegenerative pathology related to oxidative damage. We investigated the concentration of ApoD in the blood of healthy control subjects and PD patients with mild-to-moderate neurological impairment. ApoD plasma levels were measured using sandwich enzyme-linked immunosorbent assays (ELISA) in 90 healthy subjects (aging-analysis cohort) and in 66 PD patients at different stages compared with 19 age-matched healthy subjects. Significant age-related increase of ApoD was detected in subjects older than 65 years of age (p<0.002). In PD patients, a significant increase in ApoD plasma concentration was found compared with healthy subjects of the same age (p<0.05). ApoD and PD stage are significantly correlated (p<0.05). ApoD might be a valid marker for the progression of PD

Intestinal epithelial barrier integrity investigated by label-free techniques in ulcerative colitis patients

The intestinal epithelial barrier, among other compartments such as the mucosal immune system, contributes to the maintenance of intestinal homeostasis. Therefore, any disturbance within the epithelial layer could lead to intestinal permeability and promote mucosal inflammation. Considering that disintegration of the intestinal epithelial barrier is a key element in the etiology of ulcerative colitis, further assessment of barrier integrity could contribute to a better understanding of the role of epithelial barrier defects in ulcerative colitis (UC), one major form of chronic inflammatory bowel disease. Herein, we employ fast, non-destructive, and label-free non-linear methods, namely coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG), two-photon excited fluorescence (TPEF), and two-photon fluorescence lifetime imaging (2P-FLIM), to assess the morpho-chemical contributions leading to the dysfunction of the epithelial barrier. For the first time, the formation of epithelial barrier gaps was directly visualized, without sophisticated data analysis procedures, by the 3D analysis of the colonic mucosa from severely inflamed UC patients. The results were compared with histopathological and immunofluorescence images and validated using transmission electron microscopy (TEM) to indicate structural alterations of the apical junction complex as the underlying cause for the formation of the epithelial barrier gaps. Our findings suggest the potential advantage of non-linear multimodal imaging is to give precise, detailed, and direct visualization of the epithelial barrier in the gastrointestinal tract, which can be combined with a fiber probe for future endomicroscopy measurements during real-time in vivo imaging

Robot-assisted stair climbing training on postural control and sensory integration processes in chronic post-stroke patients: a randomized controlled clinical trial

Background: Postural control disturbances are one of the important causes of disability in stroke patients affecting balance and mobility. The impairment of sensory input integration from visual, somatosensory and vestibular systems contributes to postural control disorders in post-stroke patients. Robot-assisted gait training may be considered a valuable tool in improving gait and postural control abnormalities. Objective: The primary aim of the study was to compare the effects of robot-assisted stair climbing training against sensory integration balance training on static and dynamic balance in chronic stroke patients. The secondary aims were to compare the training effects on sensory integration processes and mobility. Methods: This single-blind, randomized, controlled trial involved 32 chronic stroke outpatients with postural instability. The experimental group (EG, n = 16) received robot-assisted stair climbing training. The control group (n = 16) received sensory integration balance training. Training protocols lasted for 5 weeks (50 min/session, two sessions/week). Before, after, and at 1-month follow-up, a blinded rater evaluated patients using a comprehensive test battery. Primary outcome: Berg Balance Scale (BBS). Secondary outcomes:10-meter walking test, 6-min walking test, Dynamic gait index (DGI), stair climbing test (SCT) up and down, the Time Up and Go, and length of sway and sway area of the Center of Pressure (CoP) assessed using the stabilometric assessment. Results: There was a non-significant main effect of group on primary and secondary outcomes. A significant Time × Group interaction was measured on 6-min walking test (p = 0.013) and on posturographic outcomes (p = 0.005). Post hoc within-group analysis showed only in the EG a significant reduction of sway area and the CoP length on compliant surface in the eyes-closed and dome conditions. Conclusion: Postural control disorders in patients with chronic stroke may be ameliorated by robot-assisted stair climbing training and sensory integration balance training. The robot-assisted stair climbing training contributed to improving sensorimotor integration processes on compliant surfaces. Clinical trial registration (NCT03566901)

Pseudo-HE images derived from CARS/TPEF/SHG multimodal imaging in combination with Raman-spectroscopy as a pathological screening tool

Due to the steadily increasing number of cancer patients worldwide the early diagnosis and treatment of cancer is a major field of research. The diagnosis of cancer is mostly performed by an experienced pathologist via the visual inspection of histo-pathological stained tissue sections. To save valuable time, low quality cryosections are frequently analyzed with diagnostic accuracies that are below those of high quality embedded tissue sections. Thus, alternative means have to be found that enable for fast and accurate diagnosis as the basis of following clinical decision making

Good Agreement Between Modeled and Measured Sulfur and Nitrogen Deposition in Europe, in Spite of Marked Differences in Some Sites

Atmospheric nitrogen and sulfur deposition is an important effect of atmospheric pollution and may affect forest ecosystems positively, for example enhancing tree growth, or negatively, for example causing acidification, eutrophication, cation depletion in soil or nutritional imbalances in trees. To assess and design measures to reduce the negative impacts of deposition, a good estimate of the deposition amount is needed, either by direct measurement or by modeling. In order to evaluate the precision of both approaches and to identify possible improvements, we compared the deposition estimates obtained using an Eulerian model with the measurements performed by two large independent networks covering most of Europe. The results are in good agreement (bias &lt;25%) for sulfate and nitrate open field deposition, while larger differences are more evident for ammonium deposition, likely due to the greater influence of local ammonia sources. Modeled sulfur total deposition compares well with throughfall deposition measured in forest plots, while the estimate of nitrogen deposition is affected by the tree canopy. The geographical distribution of pollutant deposition and of outlier sites where model and measurements show larger differences are discussed

Characterization of Upper Limb Impairments at Body Function, Activity, and Participation in Persons With Multiple Sclerosis by Behavioral and EMG Assessment: A Cross-Sectional Study

Background: Multiple sclerosis (MS) is a chronic inflammatory demyelinating and disabling disease which primarily affects individuals in their early life between 20 and 40 years of age. MS is a complex condition, which may lead to a variety of upper limb (UL) dysfunctions and functional deficits. Objective: To explore upper limb impairments at body function, activity, and participation in persons with MS (PwMS) and severe hand dexterity impairment by behavioral and surface electromyography (sEMG) assessments. Methods: This observational cross-sectional study involved 41 PwMS with severe hand dexterity impairment stratified according to the Expanded Disability Status Scale (EDSS) into mild-moderate (n = 17; EDSS, 1-5.5), severe ambulant (n = 15; EDSS, 6-6.5), and severe nonambulant (n = 9; EDSS, 7-9.5). Behavioral outcome measures exploring body function, activity, and participation were administered. The sEMG activity of six upper limb muscles of the most affected side was measured during a reaching task. Results: The most severe group was significantly older and more affected by secondary progressive MS than the other two groups. Positive significant associations between UL deterioration and impairments at different International Classification of Functioning, Disability, and Health domains were noted in the most severe group. The progressive decline in manual dexterity was moderately to strongly associated with the deterioration of the overall UL activity (\u3c1 = 0.72; p &lt; 0.001) and disuse (amount of use \u3c1 = 0.71; p &lt; 0.001; quality of movement \u3c1 = 0.77; p &lt; 0.001). There was a low correlation between manual dexterity and UL function (\u3c1 = 0.33; p = 0.03). The muscle activation pattern investigated by sEMG was characterized by a decrease in modularity and timing delay in the wrist extensor muscles activation in the severe ambulant patients (EDSS, 6-6.5). Similar impairments were observed in the proximal muscles (anterior deltoid) in the more advanced stages (EDSS 65 7). Conclusion: Behavioral assessment, together with measures of muscle activation patterns, allows investigating the pathophysiology of UL impairments in PwMS across progressive neurological disability severity to implement task-specific rehabilitation interventions