LitCovid-sentences  

PMC:7473770 / 9779-28528 JSONTXT 11 Projects

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Id Subject Object Predicate Lexical cue
T49 0-7 Sentence denotes Results
T50 8-107 Sentence denotes In total, we investigated six postmortem lung samples from Covid-19 patients (Menter et al., 2020).
T51 108-230 Sentence denotes A tissue micro-array paraffin block with samples of all six patients and the corresponding HE stain is shown in Figure 1a.
T52 231-372 Sentence denotes Information about age, gender, hospitalization, clinical, radiological and histological characteristics of all patients are shown in Table 2.
T53 373-561 Sentence denotes Before presenting the results for the six Covid-19 patients for each of the imaging levels (scales), we give an overview on the typical datasets for one exemplary sample (I), see Figure 2.
T54 562-773 Sentence denotes The typical FOVs, image quality, and appearance of the lung structure as well as the amount of data can be inferred, and inspected in the reconstructions provided online (https://doi.org/10.5281/zenodo.3892637).
T55 774-829 Sentence denotes The datasets are denoted by patient I-VI, respectively.
T56 830-1086 Sentence denotes Gray values of the tomographic reconstruction represent phase shift per voxel with edge length v⁢x, the local electron density difference to the average paraffin can be computed by(1) Δρe(r)=φvx(r)vx⋅λ⋅r0,with wavelength λ and r0 classical electron radius.
T57 1087-1096 Sentence denotes Figure 2.
T58 1098-1195 Sentence denotes Overview of reconstruction volumes, exemplified for a punch biopsy of pulmonary autopsy sample I.
T59 1196-1670 Sentence denotes (a) Virtual section through the stitched reconstruction volume with indicated position for the 1 mm biopsy punch. (b) Virtual section through the reconstruction of the 1 mm biopsy punch volume with indicated position for the cone-beam dataset. (c) Virtual section through the cone beam dataset. (d) Image of an HE-stained histological section, which is in close proximity to the virtual slice in (a). (e) 3D views of the biopsy punch. (f) 3D views of the cone-beam datasets.
T60 1671-1773 Sentence denotes Scale bars: (a) 500⁢μ⁢m and (b,c) 100⁢μ⁢m. The entire reconstruction volume is visualized in Video 1. 
T61 1774-1782 Sentence denotes Video 1.
T62 1784-1852 Sentence denotes A video showing a fly-through the reconstruction volume of sample I.
T63 1853-1942 Sentence denotes First the parallel beam data set is shown, followed by the cone beam zoom reconstruction.
T64 1944-1974 Sentence denotes Reconstructed electron density
T65 1975-2091 Sentence denotes Next, we present representative slices through the reconstruction volumes of all samples for all acquisition scales.
T66 2092-2206 Sentence denotes Figure 3 presents the stitched reconstruction volumes, recorded under conditions of local tomography, see Table 3.
T67 2207-2578 Sentence denotes Conventional HE-stained histology images of all samples are shown in Appendix 1—figure 1. Since these volumes are computed from stitching up to 20 individual tomograms, the question arises to which extend the image quality is limited by potential artifacts of local tomography, that is, errors due to the fact that part of the sample is outside the reconstruction volume.
T68 2579-2768 Sentence denotes For this reason, 1 mm punches were taken after the stitched overview and rescanned in the parallel beam configuration, without local tomography conditions, since they fitted within the FOV.
T69 2769-2852 Sentence denotes The results are presented in Figure 4, and validate the previous stitching results.
T70 2853-2967 Sentence denotes The 1 mm punches then also provided an appropriate size for the cone-beam recordings, which are shown in Figure 5.
T71 2968-3090 Sentence denotes Importantly, in each scan the previous level guided the choice for the next FOV and informed about the larger environment.
T72 3091-3190 Sentence denotes In the following, we briefly discuss the samples one-by-one, with regard to all acquisition scales.
T73 3191-3300 Sentence denotes A comparison of morphological features between conventional and virtual histology is shown in the Appendix 1.
T74 3301-3310 Sentence denotes Figure 3.
T75 3312-3385 Sentence denotes Stitched parallel-beam reconstructions for full pulmonary samples (I–VI).
T76 3386-3491 Sentence denotes Representative virtual sections through the reconstruction volumes of full biopsies (I–VI), respectively.
T77 3492-3503 Sentence denotes Scale bars:
T78 3504-3512 Sentence denotes 500⁢μ⁢m.
T79 3513-3522 Sentence denotes Figure 4.
T80 3524-3585 Sentence denotes Parallel-beam reconstructions for 1 mm biopsy punches (I–VI).
T81 3586-3732 Sentence denotes Representative virtual sections through the reconstruction volumes of the 1 mm punches into the volumes of the full biopsies (I–VI), respectively.
T82 3733-3867 Sentence denotes The fact that the punches are isolated results in higher image quality, since the errors associated with local tomography are avoided.
T83 3868-3879 Sentence denotes Scale bars:
T84 3880-3888 Sentence denotes 100⁢μ⁢m.
T85 3889-3898 Sentence denotes Figure 5.
T86 3900-4045 Sentence denotes Cone-beam reconstructions for biopsy punches (I–VI), shown for approximately the same slices as in Figure 4 for the parallel beam reconstruction.
T87 4046-4245 Sentence denotes Virtual sections through the reconstruction volumes of the cone-beam recordings corresponding to sections in Figure 4, obtained by the parallel beam configuration, for biopsies (I–VI) , respectively.
T88 4246-4257 Sentence denotes Scale bars:
T89 4258-4266 Sentence denotes 100⁢μ⁢m.
T90 4268-4276 Sentence denotes Sample I
T91 4277-4551 Sentence denotes By conventional histopathological assessment, the peribronchial alveolar parenchyma of sample I showed DAD with focal formation of hyaline membranes adjacent to the epithelial lining, moderate lymphocytic interstitial pneumonia and singular thrombi in small pulmonary veins.
T92 4552-4773 Sentence denotes There is a moderate hypertrophy of the muscular media in smaller pre- and post-capillary blood vessels with desquamation of the endothelial cell layer as well as mild centrilobular emphysema (original magnification 100×).
T93 4774-4863 Sentence denotes In PC-CT, enlarged alveolar septa with pronounced lymphocytic inflammation are displayed.
T94 4864-4999 Sentence denotes The reconstruction volume contains a large artery filled with erythrocytes (Figure 3-I, lower left), which bifurcates into two vessels.
T95 5000-5065 Sentence denotes This area was then selected for the 1 mm biopsy punch extraction.
T96 5066-5153 Sentence denotes The cone-beam zoom tomogram was then centered around the perimeter of the blood vessel.
T97 5154-5295 Sentence denotes This volume is particularly well suited to investigate the connective tissue including elastic fibers and collagen, as well as smooth muscle.
T98 5297-5306 Sentence denotes Sample II
T99 5307-5513 Sentence denotes Histomorphological analysis shows peribronchial alveolar parenchyma with hyperemia of capillary and post-capillary blood vessels, as well as a moderate centrilobular emphysema (original magnification 100×).
T100 5514-5597 Sentence denotes On the level of blood vessels, both blood-filled and empty vessels are discernible.
T101 5598-5675 Sentence denotes It should be noted that septa with signs of parallel capillaries are visible.
T102 5676-5786 Sentence denotes In the reconstruction volume of the zoom tomogram, a single vessel can be easily tracked over large distances.
T103 5788-5798 Sentence denotes Sample III
T104 5799-5987 Sentence denotes The sample consists of peribronchial alveolar parenchyma showing prominent multifocal neutrophilic capillaritis as well as a moderate centrilobular emphysema (original magnification 100×).
T105 5988-6091 Sentence denotes In PC-CT, septa with again similar physiological size and distribution emerge, with moderate emphysema.
T106 6092-6173 Sentence denotes The bottom part of the sample contains a fibrous area near a larger blood vessel.
T107 6174-6251 Sentence denotes The zoom tomogram shows a single septum, a blood vessel and a fibrous region.
T108 6253-6262 Sentence denotes Sample IV
T109 6263-6463 Sentence denotes Histomorphological analysis shows peribronchial alveolar parenchyma with marked lymphocytic interstitial pneumonia, multifocal venous thrombi and focal intraalveolar fibrin deposition in terms of DAD.
T110 6464-6547 Sentence denotes Furthermore, there is a mild centrilobular emphysema (original magnification 100×).
T111 6548-6652 Sentence denotes In PC-CT, a network of thin septa, thrombi and emphysema, as well as a large empty blood vessel appears.
T112 6653-6707 Sentence denotes Electron-rich diffuse black granules are also visible.
T113 6708-6792 Sentence denotes The biopsy punch was selected to contain the empty blood vessel, some small thrombi.
T114 6793-6856 Sentence denotes It also includes thin septa and tissue embedded dirt-particles.
T115 6857-6972 Sentence denotes The zoom tomogram covered tissue with black granules as well as a band of inflammatory cells next to a septum wall.
T116 6974-6982 Sentence denotes Sample V
T117 6983-7287 Sentence denotes By conventional histological assessment, Sample V consists of peribronchial alveolar parenchyma showing massive lymphocytic interstitial pneumonia with ubiquitous hyaline membranes superimposed on the alveolar walls, neutrophilic capillaritis and multifocal post-capillary thrombi in terms of severe DAD.
T118 7288-7423 Sentence denotes Furthermore, bronchialized alveolar epithelial cells show cytopathic changes and multifocal desquamation, as does alveolar macrophages.
T119 7424-7577 Sentence denotes Focally, accumulation of intraalveolar neutrophilic granulocytes in the sense of a florid bronchopneumonia can be observed (original magnification 100×).
T120 7578-7752 Sentence denotes PC-CT data give rise to alterations of the overall morphology due to Covid-19, including substantial inflammation, pronounced hyaline membranes, and high load of lymphocytes.
T121 7753-7858 Sentence denotes The biopsy punch was chosen to include areas with increased presence of hyaline membrane and lymphocytes.
T122 7859-7987 Sentence denotes A blood vessel splitting into several smaller blood vessels is easily recognized when browsing through the reconstructed volume.
T123 7988-8103 Sentence denotes Noteworthy, different cell types as macrophages, T-cells or erythrocytes can be distinguished in the zoom tomogram.
T124 8105-8114 Sentence denotes Sample VI
T125 8115-8265 Sentence denotes Histomorphological analysis shows peribronchial alveolar parenchyma with lymphocytic interstitial pneumonitis and a singular thrombus in a small vein.
T126 8266-8340 Sentence denotes The interstitium of the alveolar septae is widened by myogenic metaplasia.
T127 8341-8404 Sentence denotes Adjacent, centrilobular emphysema and anthracosis are observed.
T128 8405-8555 Sentence denotes The bronchial mucosa shows varying degrees of lymphocytic inflammation in the sense of chronic bronchitis/bronchiolitis (original magnification 100×).
T129 8556-8710 Sentence denotes From PC-CT reconstructions, the sample consists of thin alveoli (Figure 3VI, upper left) evolving into compact, fibrotic tissue (Figure 3VI, lower right).
T130 8711-8766 Sentence denotes The amount of lymphocytes is rather low in this sample.
T131 8767-8842 Sentence denotes Black granules and some thrombi are embedded within the bulky tissue parts.
T132 8843-9005 Sentence denotes The biopsy punch covers the region of transition from alveoli to fibrotic tissue, containing also a thrombus and capillaries as identified from the zoom tomogram.
T133 9007-9069 Sentence denotes Visualization of pathologies, segmentation, and quantification
T134 9070-9235 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 9236-9347 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 9348-9461 Sentence denotes Based on the tissue mask the distances for each tissue voxel to the next voxel containing oxygen were determined.
T137 9462-9629 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 9630-9860 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 9861-10009 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 10010-10152 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 10153-10162 Sentence denotes Figure 6.
T142 10164-10204 Sentence denotes Tissue compactness and distance metrics:
T143 10205-10317 Sentence denotes The 3D reconstructions of the lung tissue were analyzed in terms of specific surface and characteristic lengths.
T144 10318-10378 Sentence denotes The workflow is sketched for sample V in the top part (a–g).
T145 10379-10435 Sentence denotes In a first step, the tissue was segmented using Ilastik.
T146 10436-10498 Sentence denotes A slice of the reconstructed electron density is shown in (a).
T147 10499-10735 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 10736-10846 Sentence denotes Especially around vessels and larger alveoli, the distances are larger. (d) Zoom into an area around a vessel.
T149 10847-11165 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 11166-11279 Sentence denotes In order to compare all samples, the count of voxels was normalized by the total volume of the respective sample.
T151 11280-11463 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 11464-11533 Sentence denotes Double logarithmic scale, bin width of the distribution of distances:
T153 11534-11540 Sentence denotes 1 v⁢x.
T154 11541-11567 Sentence denotes Scale bars: (a–c) 100⁢μ⁢m.
T155 11568-11651 Sentence denotes The distribution of the distances obtained for a given slice is shown in Figure 6e.
T156 11652-11837 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 11838-11976 Sentence denotes Figure 6h shows the distribution of the tissue-air distances (histogram) for all samples, following the workflow illustrated in Figure 6e.
T158 11977-12030 Sentence denotes The binning of distances was set to one voxel length.
T159 12031-12144 Sentence denotes The figure underlines the high diversity of the tissue structure which could already be seen in the 3D histology.
T160 12145-12252 Sentence denotes Further, it directly informs about the specific surface SV, which is given by the first point of the graph.
T161 12253-12335 Sentence denotes The corresponding parameters and metrics are tabulated in Table 1 for all samples.
T162 12336-12440 Sentence denotes Additionally, the mean concentration of lymphocytes cl within the lung tissue is listed for all samples.
T163 12441-12539 Sentence denotes The values quantify the general structure of the tissue which is qualitatively discernible by eye.
T164 12540-12669 Sentence denotes Samples with a high amount of swollen, inflamed blood vessels and thick hyaline membranes exhibit a larger characteristic length.
T165 12670-12807 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 12808-12888 Sentence denotes Hence, the results cannot be directly compared to the paraffin embedded samples.
T167 12889-13017 Sentence denotes Further, the analysis of the lymphocyte concentration was performed since no lymphocytes were found in the reconstructed volume.
T168 13018-13131 Sentence denotes The low values of Lc and dO2¯ for sample II correlate with the lack of ground-glass opacification in clinical CT.
T169 13132-13250 Sentence denotes Based on the extracted structural parameters, the degree of inflammation and swelling of lung tissue can be evaluated.
T170 13251-13371 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 13372-13571 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 13572-13580 Sentence denotes Table 1.
T173 13582-13930 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 13931-13942 Sentence denotes Patient no.
T175 13944-14000 Sentence denotes SV (%) Lc (μm) dO2¯ (μm) c l   ( 10 5 / m m 3 )
T176 14001-14029 Sentence denotes I 13.87 9.4 5.9±5.3 16.0
T177 14030-14059 Sentence denotes II 46.56 2.8 2.1±1.0 14.1
T178 14060-14089 Sentence denotes III 33.75 3.9 2.5±1.5 4.4
T179 14090-14118 Sentence denotes IV 25.90 5.0 3.2±2.3 7.1
T180 14119-14146 Sentence denotes V 19.28 6.7 3.6±2.1 4.8
T181 14147-14175 Sentence denotes VI 11.87 11.0 9.1±10 6.1
T182 14176-14305 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 14306-14413 Sentence denotes Volumetric renderings in Figure 7a and b demonstrate particular attachment of fibrin to the alveolar walls.
T184 14414-14559 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 14560-14630 Sentence denotes In Figure 7f, hyaline membranes of neighboring alveoles are indicated.
T186 14631-14807 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 14808-14817 Sentence denotes Figure 7.
T188 14819-14924 Sentence denotes Rendering of hyaline membrane attached to alveolar walls (patient V, parallel beam-scan of a 1 mm punch).
T189 14925-15207 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 15208-15487 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 15488-15514 Sentence denotes Scale bars: (c–e) 300⁢μ⁢m.
T192 15515-15722 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 15723-15835 Sentence denotes Further, lymphocytes (red) were identified based on the automated cell segmentation (see Materials and methods).
T194 15836-15964 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 15965-16161 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 16162-16269 Sentence denotes This concept was then translated to a 3D-stitched volume of an entire tissue block as shown in Figure 8f,g.
T197 16270-16279 Sentence denotes Figure 8.
T198 16281-16442 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 16443-16670 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 16671-16914 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 16915-17048 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 17049-17089 Sentence denotes The segmentation was performed manually.
T203 17090-17236 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 17237-17332 Sentence denotes The separation starts with the creation of a branch from the blood vessel (arrow in slice 336).
T205 17333-17430 Sentence denotes In slice 326, 1.7⁢μ⁢m above slice 336, this branch evolves into an empty and separated capillary.
T206 17431-17496 Sentence denotes Another 2⁢μ⁢m above, the capillary is entirely filled with cells.
T207 17497-17579 Sentence denotes Further 2.3⁢μ⁢m, the capillary is empty again and has a diameter of about 2.8⁢μ⁢m.
T208 17580-17706 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 17707-17847 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 17848-17956 Sentence denotes The 3D shape of the blood vessel is illustrated by the 3D rendering of the segmentation, shown in Figure 9c.
T211 17957-18104 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 18105-18114 Sentence denotes Figure 9.
T213 18116-18185 Sentence denotes Segmentation of the blood vessel network, exemplified for biopsy (V).
T214 18186-18299 Sentence denotes (a) Series of slices in z-direction illustrate the separation of a capillary (≈5μm diameter) from a blood vessel.
T215 18300-18341 Sentence denotes Red arrow marks the separating capillary.
T216 18342-18532 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 18533-18729 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 18730-18741 Sentence denotes Scale bars:
T219 18742-18749 Sentence denotes 50⁢μ⁢m.