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Evaluating cellularity and structural connectivity on whole brain slides using a custom-made digital pathology pipeline.

ABSTRACT: AIMS:In brain research, the histopathological examination of coronar whole-brain slides provides important insights into spatial disease characteristics. Regarding brain tumor research, this enables visualization of tumor heterogeneity, infiltration patterns and the relationship with the surrounding brain parenchyma. The precise correlation between radiological imaging and post-mortem brains is of special interest. NEW METHOD:We developed a wide-field slide scanner, comprising a microscope, a high-precision remotely controllable x-y-stage, a camera and a computer workstation, for automatically scanning uncommonly large formats. We analyzed whole brain slides of three patients and constructed cellularity heatmaps and fiber tract maps using a custom-made image processing pipeline. RESULTS:The obtained cellularity heatmaps allow for distinguishing compact tumor (5714?±?1786 cells/mm², mean?±?standard deviation) from white matter (3581?±?828 cells/mm²) and grey matter (2473?±?716 cells/mm²). Compared to magnetic resonance imaging, the proposed histopathological work-up (i) reveals a larger zone of tumor infiltration around the compact tumor areas and (ii) shows how pre-existing tracts are displaced by the tumor bulk. Moreover, we highlight differences in the histological tumor growth pattern of two different radiological progression subtypes. COMPARISON WITH EXISTING METHOD(S):Compared to existing (commercial) solutions, our slide scanning solution is adaptable and cost-efficient. Moreover, we showcase potential clinical applications by mapping whole brain histology to magnetic resonance imaging. CONCLUSIONS:We herein provide instructions on how to (i) construct a custom-built slide scanner capable of scanning arbitrary slide formats, (ii) automatically evaluate the cell density and (iii) perform fiber tracking on whole brain slides.

SUBMITTER: Roetzer T

PROVIDER: S-EPMC6269083 | biostudies-other | 2019 Jan

REPOSITORIES: biostudies-other

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Evaluating cellularity and structural connectivity on whole brain slides using a custom-made digital pathology pipeline.

Roetzer Thomas T Leskovar Konrad K Peter Nadine N Furtner Julia J Muck Martina M Augustin Marco M Lichtenegger Antonia A Nowosielski Martha M Hainfellner Johannes A JA Baumann Bernhard B Woehrer Adelheid A

Journal of neuroscience methods 20181024

<h4>Aims</h4>In brain research, the histopathological examination of coronar whole-brain slides provides important insights into spatial disease characteristics. Regarding brain tumor research, this enables visualization of tumor heterogeneity, infiltration patterns and the relationship with the surrounding brain parenchyma. The precise correlation between radiological imaging and post-mortem brains is of special interest.<h4>New method</h4>We developed a wide-field slide scanner, comprising a m ...[more]

PMID: 30365968

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Project description:We sought to evaluate visual performance and satisfaction with ready-made spectacles (RMS) in Chinese school-aged children with uncorrected refractive error.Randomized, double-blind, clinical trial.Junior high school students from urban Guangzhou, China, aged approximately 12 to 15 years with > or =1 diopter (D) of uncorrected spherical equivalent (SE) refractive error. Students were excluded with > or =2.00 D astigmatism, > or =2 D myopic anisometropia, and > or =1 D hyperopic anisometropia and ocular disease affecting vision.Refractive error was determined by cycloplegic subjective refraction. Students were randomly assigned to receive RMS or custom spectacles (CS) and assessed after 1 month of use. We required 175 students to complete in each arm to be able to measure a 15% difference in compliance.Compliance with spectacles lens wear, patterns of use, vision, symptoms, and perceived value.Screening identified 965 of 4607 (20.9%) students with reduced distance vision; 212 of the 965 (22.0%) refused evaluation and 187 of the 965 (20.8%) had <1 D of SE refractive error. Sixty-one (6.3%) were referred for further evaluation and the remaining 495 (51.3%) participated. Social, demographic, and ocular parameters were similar in the 2 groups. Average SE refractive error was -2.57+/-1.31 (mean value +/- standard deviation [SD]). Spectacle vision (Snellen acuity, mean +/- SD) was worse with RMS in the eye with lower SE (20/25(-0.5)+/-0.9 lines vs 20/25(+1)+/-0.7 lines; P = 0.004) and higher SE (20/25(-2)+/-1.2 lines vs 20/25(+1)+/-0.8; P<0.001). There were no differences (P>0.05) in the rate of use (94.3% vs 92.2%), wearing to the 1-month visit (46.9% vs 51.5%), planned use (93.3% vs 93.7%), value (89.5% vs 91.7% "moderate or high value or most valued possession"), or symptoms (blur, 21.1% vs 19.4% [P = 0.8] and other symptoms [P>0.2]).Although visual acuity was better with CS, no difference was found in acceptability in this population of students with predominantly simple myopic refractive error. This study supports the use of RMS in a school-based refractive services program, saving costs and improving the logistics of service delivery.

Project description:Objective:Ready-made spectacles have been suggested as a less resource-intensive treatment for the millions of people living with uncorrected refractive error (URE) in low-income environments. In spite of this interest, there have been no published economic evaluations examining the cost-effectiveness of ready-made spectacles. This study aims to determine the relative cost-effectiveness of offering ready-made spectacles (RMS) relative to no intervention as well as the relative cost-effectiveness of custom-made spectacles (CS) relative to RMS to treat URE. Methods and analysis:The relative cost-effectiveness of RMS relative to CS and no intervention was tested through a cost-effectiveness analysis from the health service provider perspective conducted alongside a double-masked randomised controlled trial in an urban hospital in Delhi, India. Participants were adults aged 18-45 years with ?1?dioptre (D) of URE. Results:There was no significant difference between the effectiveness of the CS and RMS interventions in improving visual acuity, but the CS was over four times the price of the RMS per patient (204 INR (US$2.42) and 792 INR (US$11.22)). The cost per unit improvement in logarithm of the minimum angle of resolution (logMAR) relative to baseline with the RMS intervention was 407 INR (US$4.35). Existing estimates of utility resulting from improvements in visual acuity result in incremental cost per quality-adjusted life years gained of between 212 INR and 1137 INR (US$0.44-US$23.74) depending on the source of the utility estimate and assumed expected life of the spectacles. Conclusion:RMS represent a significantly cost-effective option for spectacle provision in low-resource settings. The RMS programme was substantially cheaper than an equivalent CS intervention while being effective in improving visual acuity for the majority of adults with refractive error in this setting. These findings provide further support for including RMS in programmes to address URE. Trial registration number:NCT00657670, Results.

Dataset Information

Evaluating cellularity and structural connectivity on whole brain slides using a custom-made digital pathology pipeline.

Publications

Evaluating cellularity and structural connectivity on whole brain slides using a custom-made digital pathology pipeline.

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