PMC:7473770 / 18786-28528 JSONTXT 10 Projects

Annnotations TAB TSV DIC JSON TextAE

Id Subject Object Predicate Lexical cue
T133 0-62 Sentence denotes Visualization of pathologies, segmentation, and quantification
T134 63-228 Sentence denotes The overview scans of all paraffin embedded Covid-19 positive samples and one biopsy of a hydrated control lung were analyzed in terms of structural characteristics.
T135 229-340 Sentence denotes The top row of Figure 6 shows the workflow of the analysis on the example of the 3D reconstruction of sample V.
T136 341-454 Sentence denotes Based on the tissue mask the distances for each tissue voxel to the next voxel containing oxygen were determined.
T137 455-622 Sentence denotes For the analysis of the tissue it is mandatory to consider the three-dimensionality of the samples, similar to the analysis of porous structures (Müller et al., 2002).
T138 623-853 Sentence denotes More generally, we claim that 3D histology analysis based on x-ray tomography and light sheet microscopy (Power and Huisken, 2017) is required to quantitatively understand functional tissue properties based on its 3D architecture.
T139 854-1002 Sentence denotes Here, this can also be seen in Figure 6d, which shows a zoom of the distance analysis around a small blood vessel which is marked with a yellow box.
T140 1003-1145 Sentence denotes While the wall thickness appears quite homogeneous in the 2d slice, the distance analysis reveals that the vessel is thicker on the top right.
T141 1146-1155 Sentence denotes Figure 6.
T142 1157-1197 Sentence denotes Tissue compactness and distance metrics:
T143 1198-1310 Sentence denotes The 3D reconstructions of the lung tissue were analyzed in terms of specific surface and characteristic lengths.
T144 1311-1371 Sentence denotes The workflow is sketched for sample V in the top part (a–g).
T145 1372-1428 Sentence denotes In a first step, the tissue was segmented using Ilastik.
T146 1429-1491 Sentence denotes A slice of the reconstructed electron density is shown in (a).
T147 1492-1728 Sentence denotes Based on the segmentation, the areas of air which are directly connected and potentially filled with oxygen (or blood) are masked out (b). (c) For each of the remaining tissue voxels the shortest possible distance to air was calculated.
T148 1729-1839 Sentence denotes Especially around vessels and larger alveoli, the distances are larger. (d) Zoom into an area around a vessel.
T149 1840-2158 Sentence denotes Further analysis is based on the distance distribution shown in (e). (f) Volume rendering of the reconstructed electron density, with (g) showing the corresponding 3D distance map. (h) Based on the tissue segmentation of all samples, the distance from the tissue interior to the closest air compartment was calculated.
T150 2159-2272 Sentence denotes In order to compare all samples, the count of voxels was normalized by the total volume of the respective sample.
T151 2273-2456 Sentence denotes The specific surface area SV (represented by the first value of each curve), the characteristic length Lc and the mean distance dO2¯ for each sample was calculated based on this data.
T152 2457-2526 Sentence denotes Double logarithmic scale, bin width of the distribution of distances:
T153 2527-2533 Sentence denotes 1 v⁢x.
T154 2534-2560 Sentence denotes Scale bars: (a–c) 100⁢μ⁢m.
T155 2561-2644 Sentence denotes The distribution of the distances obtained for a given slice is shown in Figure 6e.
T156 2645-2830 Sentence denotes The swelling of the alveolar walls as well as the inflamed blood vessels can be identified by comparing the reconstructed electron density and the 3D-distance map (see Figure 6f and g).
T157 2831-2969 Sentence denotes Figure 6h shows the distribution of the tissue-air distances (histogram) for all samples, following the workflow illustrated in Figure 6e.
T158 2970-3023 Sentence denotes The binning of distances was set to one voxel length.
T159 3024-3137 Sentence denotes The figure underlines the high diversity of the tissue structure which could already be seen in the 3D histology.
T160 3138-3245 Sentence denotes Further, it directly informs about the specific surface SV, which is given by the first point of the graph.
T161 3246-3328 Sentence denotes The corresponding parameters and metrics are tabulated in Table 1 for all samples.
T162 3329-3433 Sentence denotes Additionally, the mean concentration of lymphocytes cl within the lung tissue is listed for all samples.
T163 3434-3532 Sentence denotes The values quantify the general structure of the tissue which is qualitatively discernible by eye.
T164 3533-3662 Sentence denotes Samples with a high amount of swollen, inflamed blood vessels and thick hyaline membranes exhibit a larger characteristic length.
T165 3663-3800 Sentence denotes Note, that the control lung was prepared in a hydrated environment and shrinking due to further preparation of the sample does not occur.
T166 3801-3881 Sentence denotes Hence, the results cannot be directly compared to the paraffin embedded samples.
T167 3882-4010 Sentence denotes Further, the analysis of the lymphocyte concentration was performed since no lymphocytes were found in the reconstructed volume.
T168 4011-4124 Sentence denotes The low values of Lc and dO2¯ for sample II correlate with the lack of ground-glass opacification in clinical CT.
T169 4125-4243 Sentence denotes Based on the extracted structural parameters, the degree of inflammation and swelling of lung tissue can be evaluated.
T170 4244-4364 Sentence denotes E.g. patient II has the highest surface area volume-ratios while sample I and VI have a relatively low specific surface.
T171 4365-4564 Sentence denotes Larger characteristic lengths may also be indicative of inflammation and the formation of hyaline membranes, which will be evaluated in the following based on ROI and high-resolution reconstructions.
T172 4565-4573 Sentence denotes Table 1.
T173 4575-4923 Sentence denotes Results of the analysis of tissue characteristics: specific surface area SV, characteristic length Lc and mean distance dO2¯ and standard deviation from all tissue voxels to air as well as the mean concentration of lymphocytes cl for all six Covid-19 positive samples as well as for one control sample. Colors match the distance graphs in Figure 6.
T174 4924-4935 Sentence denotes Patient no.
T175 4937-4993 Sentence denotes SV (%) Lc (μm) dO2¯ (μm) c l   ( 10 5 / m m 3 )
T176 4994-5022 Sentence denotes I 13.87 9.4 5.9±5.3 16.0
T177 5023-5052 Sentence denotes II 46.56 2.8 2.1±1.0 14.1
T178 5053-5082 Sentence denotes III 33.75 3.9 2.5±1.5 4.4
T179 5083-5111 Sentence denotes IV 25.90 5.0 3.2±2.3 7.1
T180 5112-5139 Sentence denotes V 19.28 6.7 3.6±2.1 4.8
T181 5140-5168 Sentence denotes VI 11.87 11.0 9.1±10 6.1
T182 5169-5298 Sentence denotes CTRL (hyd.) 20.04 6.5 5.0±5.1 - Figure 7 illustrates the aggregation of hyaline membrane in the vicinity of a single alveole.
T183 5299-5406 Sentence denotes Volumetric renderings in Figure 7a and b demonstrate particular attachment of fibrin to the alveolar walls.
T184 5407-5552 Sentence denotes In cases of severe hyaline membrane formation as for this patient, this pathological alteration can be tracked throughout the volume Figure 7c–e.
T185 5553-5623 Sentence denotes In Figure 7f, hyaline membranes of neighboring alveoles are indicated.
T186 5624-5800 Sentence denotes In the 3D-context, their locations with respect to blood vessels can be inspected, see Figure 7g, which exemplifies a direct connection of hyaline membranes to the vasculature.
T187 5801-5810 Sentence denotes Figure 7.
T188 5812-5917 Sentence denotes Rendering of hyaline membrane attached to alveolar walls (patient V, parallel beam-scan of a 1 mm punch).
T189 5918-6200 Sentence denotes The rendered subvolume was restricted to 1.15×1.10×0.56 mm3, to contain a single alveole foremost. (a) Volume rendering of the segmented hyaline membrane in same spatial orientation as (c)-(e), which show virtual slices through the (c) top, (d) center and (e) bottom of the alveole.
T190 6201-6480 Sentence denotes For a better spatial classification, (b) gives a combination of the volume in (a) and the slice in (d). (f) Volume rendering of the entire subvolume including neighboring alveolae. (g) Zoom-in onto a major blood vessel (red) which is directly connected with the hyaline membrane.
T191 6481-6507 Sentence denotes Scale bars: (c–e) 300⁢μ⁢m.
T192 6508-6715 Sentence denotes The severeness of hyaline membrane formation is case-specific, as the yellow rendering in Figure 8a,b,d demonstrates reduced amounts of deposits for patient I in a subvolume of parallel-beam reconstructions.
T193 6716-6828 Sentence denotes Further, lymphocytes (red) were identified based on the automated cell segmentation (see Materials and methods).
T194 6829-6957 Sentence denotes For clearer visualization, each cell is rendered as a sphere with a size corresponding to the mean cell volume in Figure 8a,b,d.
T195 6958-7154 Sentence denotes Based on convolution of the cell positions with a sphere of 100⁢μ⁢m in radius, the local cell density was calculated (Töpperwien et al., 2018) and presented as 3D-maps of cells/mm3 in Figure 8c,e.
T196 7155-7262 Sentence denotes This concept was then translated to a 3D-stitched volume of an entire tissue block as shown in Figure 8f,g.
T197 7263-7272 Sentence denotes Figure 8.
T198 7274-7435 Sentence denotes Rendering of alveolar wall with hyaline membrane and quantification of lymphocyte infiltration (unstained tissue, patient I, parallel beam scan of a 1 mm punch).
T199 7436-7663 Sentence denotes The illustrations in (a–e) show a subvolume of 0.60×0.48×0.26 mm3, (f and g) this concept applied to the full tissue block of 2.57×2.99×0.98 mm3. (a) Yellow contours mark the locations of hyaline membrane in an exemplary slice.
T200 7664-7907 Sentence denotes In same spatial orientation, (b, d and f) volume rendering of soft tissue (light pink), infiltrated by hyaline membrane (yellow) and lymphocytes (red) and (c, e and g) their local cell density among the lung tissue, including air compartments.
T201 7908-8041 Sentence denotes Next, the segmentation of blood vessels is demonstrated for the example of a splitting blood vessel in the zoom tomogram of sample V.
T202 8042-8082 Sentence denotes The segmentation was performed manually.
T203 8083-8229 Sentence denotes To give an impression of the separation of a single capillary, a series of virtual slices in the xy-plane (magnified views) is shown in Figure 9a.
T204 8230-8325 Sentence denotes The separation starts with the creation of a branch from the blood vessel (arrow in slice 336).
T205 8326-8423 Sentence denotes In slice 326, 1.7⁢μ⁢m above slice 336, this branch evolves into an empty and separated capillary.
T206 8424-8489 Sentence denotes Another 2⁢μ⁢m above, the capillary is entirely filled with cells.
T207 8490-8572 Sentence denotes Further 2.3⁢μ⁢m, the capillary is empty again and has a diameter of about 2.8⁢μ⁢m.
T208 8573-8699 Sentence denotes The segmentation of the blood vessel with all its separated branches is indicated for slice 336 in Figure 9b by the red lines.
T209 8700-8840 Sentence denotes In this slice, three capillaries have already separated from the main vessel, while the fourth starts to emerge, indicated by the red arrow.
T210 8841-8949 Sentence denotes The 3D shape of the blood vessel is illustrated by the 3D rendering of the segmentation, shown in Figure 9c.
T211 8950-9097 Sentence denotes This segmentation of the blood vessel shows the potential of the datasets, which may be fully exploited in future with more advanced segmentations.
T212 9098-9107 Sentence denotes Figure 9.
T213 9109-9178 Sentence denotes Segmentation of the blood vessel network, exemplified for biopsy (V).
T214 9179-9292 Sentence denotes (a) Series of slices in z-direction illustrate the separation of a capillary (≈5μm diameter) from a blood vessel.
T215 9293-9334 Sentence denotes Red arrow marks the separating capillary.
T216 9335-9525 Sentence denotes In slice 314, the capillary is entirely filled with erythrocytes. (b) Red lines in the entire virtual slice (336) represent the contours of a manual segmentation of the blood vessel network.
T217 9526-9722 Sentence denotes Three capillaries already separated from the main vessel, while the fourth starts to emerge, indicated by the red arrow. (c) Segmentation illustrating the 3D structure of the blood vessel network.
T218 9723-9734 Sentence denotes Scale bars:
T219 9735-9742 Sentence denotes 50⁢μ⁢m.