Tile-Based Two-Dimensional Phase Unwrapping for Digital Holography Using a Modular Framework

A variety of physical and biomedical imaging techniques, such as digital holography, interferometric synthetic aperture radar (InSAR), or magnetic resonance imaging (MRI) enable measurement of the phase of a physical quantity additionally to its amplitude. However, the phase can commonly only be measured modulo 2π, as a so called wrapped phase map. Phase unwrapping is the process of obtaining the underlying physical phase map from the wrapped phase. Tile-based phase unwrapping algorithms operate by first tessellating the phase map, then unwrapping individual tiles, and finally merging them to a continuous phase map. They can be implemented computationally efficiently and are robust to noise. However, they are prone to failure in the presence of phase residues or erroneous unwraps of single tiles. We tried to overcome these shortcomings by creating novel tile unwrapping and merging algorithms as well as creating a framework that allows to combine them in modular fashion. To increase the robustness of the tile unwrapping step, we implemented a model-based algorithm that makes efficient use of linear algebra to unwrap individual tiles. Furthermore, we adapted an established pixel-based unwrapping algorithm to create a quality guided tile merger. These original algorithms as well as previously existing ones were implemented in a modular phase unwrapping C++ framework. By examining different combinations of unwrapping and merging algorithms we compared our method to existing approaches. We could show that the appropriate choice of unwrapping and merging algorithms can significantly improve the unwrapped result in the presence of phase residues and noise. Beyond that, our modular framework allows for efficient design and test of new tile-based phase unwrapping algorithms. The software developed in this study is freely available

Three-dimensional imaging of intracochlear tissue by scanning laser optical tomography (SLOT)

The presented study focuses on the application of scanning laser optical tomography (SLOT) for non-destructive visualization of anatomical structures inside the human cochlea ex vivo. SLOT is a laser-based highly efficient microscopy technique, which allows for tomographic imaging of the internal structure of transparent large-scale specimens (up to 1 cm3). Thus, in the field of otology this technique is best convenient for an ex vivo study of the inner ear anatomy. For this purpose, the preparation before imaging comprises mechanically assisted decalcification, dehydration as well as optical clearing of the cochlea samples. Here, we demonstrate results of SLOT visualizing hard and soft tissue structures of the human cochlea with an optical resolution in the micrometer range using absorption and autofluorescence as contrast mechanisms. Furthermore, we compare our results with the method of X-ray micro tomography (micro-CT, μCT) as clinical gold standard which is based only on absorption. In general, SLOT can provide the advantage of covering all contrast mechanisms known from other light microscopy techniques, such as fluorescence or scattering. For this reason, a protocol for antibody staining has been developed, which additionally enables selective mapping of cellular structures within the cochlea. Thus, we present results of SLOT imaging rodent cochleae showing specific anatomical structures such as hair cells and neurofilament via fluorescence. In conclusion, the presented study has shown that SLOT is an ideally suited tool in the field of otology for in toto visualization of the inner ear microstructure. © 2016 SPIE

Aspartylglycosaminuria in the Finnish population: Identification of two point mutations in the heavy chain of glycoasparaginase

Aspartylglycosaminuria is an inherited lysosomal storage disease caused by deficiency of glycoasparaginase (EC 3.5.1.26) and occurs with higher frequency among Finns than other populations. We have purified human glycoasparaginase and determined about 90% of the amino acid sequence of its light subunit and >70% of that of its heavy subunit by Edman degradation and mass spectrometry. Additional sequence data were obtained from the cloning and subsequent nucleotide analysis of a cDNA corresponding to the normal human glycoasparaginase gene. The enzyme is encoded by a single mRNA as a single polypeptide that is posttranslationally processed to generate the subunits and is glycosylated. After preparing first-strand cDNA from leukocyte and fibroblast total RNA, we used the polymerase chain reaction to amplify the glycoasparaginase cDNA of eight Finnish aspartylglycosaminuria patients. We demonstrate that the Finnish patients' mRNA sequence differed from the normal sequence by two single-base changes six nucleotides apart from one another in the heavy chain of glycoasparaginase. The first change resulted in the replacement of arginine by glutamine (R161Q), whereas the second change resulted in a cysteine to serine substitution (C163S). Both mutations resulted in novel restriction endonuclease sites and were present in all eight Finnish aspartylglycosaminuria patients originating from different pedigrees, but they were absent from Finnish and non-Finnish controls and a non-Finnish case of aspartylglycosaminuria. These results indicate molecular homogeneity in aspartylglycosaminuria alleles in the Finnish population

Scanning laser optical tomography for in toto imaging of the murine cochlea

The mammalian cochlea is a complex macroscopic structure due to its helical shape and the microscopic arrangements of the individual layers of cells. To improve the outcomes of hearing restoration in deaf patients, it is important to understand the anatomic structure and composition of the cochlea ex vivo. Hitherto, only one histological technique based on confocal laser scanning microscopy and optical clearing has been developed for in toto optical imaging of the murine cochlea. However, with a growing size of the specimen, e.g., human cochlea, this technique reaches its limitations. Here, we demonstrate scanning laser optical tomography (SLOT) as a valuable imaging technique to visualize the murine cochlea in toto without any physical slicing. This technique can also be applied in larger specimens up to cm3 such as the human cochlea. Furthermore, immunolabeling allows visualization of inner hair cells (otoferlin) or spiral ganglion cells (neurofilament) within the whole cochlea. After image reconstruction, the 3D dataset was used for digital segmentation of the labeled region. As a result, quantitative analysis of position, length and curvature of the labeled region was possible. This is of high interest in order to understand the interaction of cochlear implants (CI) and cells in more detail. © 2017 Nolte et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.DFG/EXC/1077/1Ministry of Lower SaxonyVolkswagenStiftun

Efficacy of a loading dose of IV salbutamol in children with severe acute asthma admitted to a PICU:a randomized controlled trial

The optimal dose regimen for intravenous (IV) treatment in children with severe acute asthma (SAA) is still a matter of debate. We assessed the efficacy of adding a salbutamol loading dose to continuous infusion with salbutamol in children admitted to a pediatric intensive care unit (PICU) with SAA. This multicentre, placebo-controlled randomized trial in the PICUs of four tertiary care children’s hospitals included children (2–18 years) with SAA admitted between 2017 and 2019. Children were randomized to receive either a loading dose IV salbutamol (15 mcg/kg, max. 750 mcg) or normal saline while on continuous salbutamol infusion. The primary outcome was the asthma score (Qureshi) 1 h after the intervention. Analysis of covariance models was used to evaluate sensitivity to change in asthma scores. Serum concentrations of salbutamol were obtained. Fifty-eight children were included (29 in the intervention group). Median baseline asthma score was 12 (IQR 10–13) in the intervention group and 11 (9–12) in the control group (p = 0.032). The asthma score 1 h after the intervention did not differ significantly between the groups (p = 0.508, β-coefficient = 0.283). The median increase in salbutamol plasma levels 10 min after the intervention was 13 μg/L (IQR 5–24) in the intervention group and 4 μg/L (IQR 0–7) in the control group (p = 0.001). Side effects were comparable between both groups. Conclusion: We found no clinical benefit of adding a loading dose IV salbutamol to continuous infusion of salbutamol, in children admitted to the PICU with SAA. Clinically significant side effects from the loading dose were not encountered.What is Known:• Pediatric asthma guidelines struggle with an evidence-based approach for the treatment of SAA beyond the initial steps of oxygen suppletion, repetitive administration of inhaled β2-agonists, and systemic steroids.• During an SAA episode, effective delivery of inhaled drugs is unpredictable due to severe airway obstruction.What is New:• This study found no beneficial effect of an additional loading dose IV salbutamol in children admitted to the PICU.• This study found no clinically significant side effects from the loading dose

Children with severe acute asthma admitted to Dutch PICUs: A changing landscape

The number of children requiring pediatric intensive care unit (PICU) admission for severe acute asthma (SAA) around the world has increased. Objectives: We investigated whether this trend in SAA PICU admissions is present in the Netherlands. Methods: A multicenter retrospective cohort study across all tertiary care PICUs in the Netherlands. Inclusion criteria were children (2-18 years) hospitalized for SAA between 2003 and 2013. Data included demographic data, asthma diagnosis, treatment, and mortality. Results: In the 11-year study period 590 children (660 admissions) were admitted to a PICU with a threefold increase in the number of admissions per year over time. The severity of SAA seemed unchanged, based on the first blood gas, length of stay and mortality rate (0.6%). More children received highflow nasal cannula (P<0.001) and fewer children needed invasive ventilation (P<0.001). In 58% of the patients the maximal intravenous (IV) salbutamol infusion rate during PICU admission was 1mcg/kg/min. However, the number of patients treated with IV salbutamol in the referring hospitals increased significantly over time (P=0.005). The proportion of steroid-naïve patients increased from 35% to 54% (P=0.004), with a significant increase in both age groups (2-4 years [P=0.026] and 5-17 years [P=0.036]). Conclusions: The number of children requiring PICU admission for SAA in the Netherlands has increased. We speculate that this threefold increase is explained by an increasing number of steroid-naïve children, in conjunction with a lowered threshold for PICU admission, possibly caused by earlier use of salbutamol IV in the referring hospitals

The association between hospital variation in curative treatment for esophagogastric cancer and health-related quality of life and survival

Background: As previous studies showed significant hospital variation in curative treatment of esophagogastric cancer, this study assesses the association between this variation and overall, cancer-specific and recurrence-free survival, and Health-Related Quality of Life (HRQoL). Methods: Patients diagnosed with potentially curable esophageal or gastric cancer between 2015 and 2018 as registered in the Netherlands Cancer Registry were included. Data on overall survival was available for all patients, data on cancer-specific and recurrence-free survival and HRQoL was available for subgroups. Patients were classified according to diagnosis in hospitals with low, medium or high probability of treatment with curative intent (LP, MP or HP). Multivariable models were used to assess the association between LP, MP and HP hospitals and HRQoL and survival. Results: This study includes 7,199 patients with esophageal, and 2,407 with gastric cancer. Overall and cancer-specific survival was better for patients diagnosed in HP versus LP hospitals for both esophageal (HR = 0.82, 95%CI:0.77–0.88 and HR = 0.82, 95%CI:0.75–0.91, respectively), and gastric cancer (HR = 0.82, 95%CI:0.73–0.92 and HR = 0.74, 95%CI:0.64–0.87, respectively). These differences disappeared after adjustments for treatment. Recurrence-free survival was worse for gastric cancer patients diagnosed in HP hospitals (HR = 1.50, 95%CI:1.14–1.96), which disappeared after adjustment for radicality of surgery. Minor, but no clinically relevant, differences in HRQoL were observed.Conclusions: Patients diagnosed in hospitals with a high probability of treatment with curative intent have a better overall and cancer-specific but not recurrence-free survival, while minor differences in HRQoL were observed.</p