Registration of serial sections: An evaluation method based on distortions of the ground truths

Registration of histological serial sections is a challenging task. Serial sections exhibit distortions and damage from sectioning. Missing information on how the tissue looked before cutting makes a realistic validation of 2D registrations extremely difficult. This work proposes methods for ground-truth-based evaluation of registrations. Firstly, we present a methodology to generate test data for registrations. We distort an innately registered image stack in the manner similar to the cutting distortion of serial sections. Test cases are generated from existing 3D data sets, thus the ground truth is known. Secondly, our test case generation premises evaluation of the registrations with known ground truths. Our methodology for such an evaluation technique distinguishes this work from other approaches. Both under- and over-registration become evident in our evaluations. We also survey existing validation efforts. We present a full-series evaluation across six different registration methods applied to our distorted 3D data sets of animal lungs. Our distorted and ground truth data sets are made publicly available.Comment: Supplemental data available under https://zenodo.org/record/428244

Comparative Analysis of Tissue Reconstruction Algorithms for 3D Histology

Motivation: Digital pathology enables new approaches that expand beyond storage, visualization or analysis of histological samples in digital format. One novel opportunity is 3D histology, where a three-dimensional reconstruction of the sample is formed computationally based on serial tissue sections. This allows examining tissue architecture in 3D, for example, for diagnostic purposes. Importantly, 3D histology enables joint mapping of cellular morphology with spatially resolved omics data in the true 3D context of the tissue at microscopic resolution. Several algorithms have been proposed for the reconstruction task, but a quantitative comparison of their accuracy is lacking. Results: We developed a benchmarking framework to evaluate the accuracy of several free and commercial 3D reconstruction methods using two whole slide image datasets. The results provide a solid basis for further development and application of 3D histology algorithms and indicate that methods capable of compensating for local tissue deformation are superior to simpler approaches.publishedVersionPeer reviewe

Fat/carbohydrate ratio but not energy density determines snack food intake and activates brain reward areas

The snack food potato chips induces food intake in ad libitum fed rats, which is associated with modulation of the brain reward system and other circuits. Here, we show that food intake in satiated rats is triggered by an optimal fat/carbohydrate ratio. Like potato chips, an isocaloric fat/carbohydrate mixture influenced whole brain activity pattern of rats, affecting circuits related e.g. to reward/addiction, but the number of modulated areas and the extent of modulation was lower compared to the snack food itself

Manganese-Enhanced Magnetic Resonance Imaging for Mapping of Whole Brain Activity Patterns Associated with the Intake of Snack Food in Ad Libitum Fed Rats

Non-homeostatic hyperphagia, which is a major contributor to obesity-related hyperalimentation, is associated with the diet’s molecular composition influencing, for example, the energy content. Thus, specific food items such as snack food may induce food intake independent from the state of satiety. To elucidate mechanisms how snack food may induce non-homeostatic food intake, it was tested if manganese-enhanced magnetic resonance imaging (MEMRI) was suitable for mapping the whole brain activity related to standard and snack food intake under normal behavioral situation. Application of the MnCl2 solution by osmotic pumps ensured that food intake was not significantly affected by the treatment. After z-score normalization and a non-affine three-dimensional registration to a rat brain atlas, significantly different grey values of 80 predefined brain structures were recorded in ad libitum fed rats after the intake of potato chips compared to standard chow at the group level. Ten of these areas had previously been connected to food intake, in particular to hyperphagia (e.g. dorsomedial hypothalamus or the anterior paraventricular thalamic nucleus) or to the satiety system (e.g. arcuate hypothalamic nucleus or solitary tract); 27 areas were related to reward/addiction including the core and shell of the nucleus accumbens, the ventral pallidum and the ventral striatum (caudate and putamen). Eleven areas associated to sleep displayed significantly reduced Mn2+-accumulation and six areas related to locomotor activity showed significantly increased Mn2+-accumulation after the intake of potato chips. The latter changes were associated with an observed significantly higher locomotor activity. Osmotic pump-assisted MEMRI proved to be a promising technique for functional mapping of whole brain activity patterns associated to nutritional intake under normal behavior

Morphological features of the porcine lacrimal gland and its compatibility for human lacrimal gland xenografting.

In this study, we present first data concerning the anatomical structure, blood supply and location of the lacrimal gland of the pig. Our data indicate that the porcine lacrimal gland may serve as a potential xenograft candidate in humans or as an animal model for engineering of a bioartificial lacrimal gland tissue construct for clinical application. For this purpose, we used different macroscopic preparation techniques and digital reconstruction of the histological gland morphology to gain new insights and important information concerning the feasibility of a lacrimal gland transplantation from pig to humans in general. Our results show that the lacrimal gland of the pig reveals a lot of morphological similarities to the analogous human lacrimal gland and thus might be regarded as a xenograft in the future. This is true for a similar anatomical location within the orbit as well as for the feeding artery supply to the organ. Functional differences concerning the composition of the tear fluid, due to a different secretory unit distribution within the gland tissue will, however, be a challenge in future investigations

Activation differences related to snack food (potato chips) vs. standard chow in representative brain structures.

<p>Statistics of activation differences due to the intake of snack food (potato chips) vs. standard chow in representative brain structures for the motor circuit (caudate putamen: CPu), the limbic system (cingulate cortex: CgCx), the reward system (shell region of the nucleus accumbens: AcbSh, core region of the nucleus accumbens: AcbC) and sleep/wake rhythm (tegmental nuclei: Teg) depicted in the left column based on the reference atlas. The middle column shows significant differences of the VBM analysis overlaid on corresponding standard T2 weighted MRI anatomy and atlas labels. The right column shows the fractional change of snack food to standard chow v (MEMRI grey values) ***p<0.001, **p<0.01.</p

Manganese accumulation in brain structures related to sleep.

<p>Significantly different (***p<0.001, **p<0.01, p*<0.05) manganese accumulation in brain structures of ad libitum fed rats with additional access to standard chow or snack food (potato chips) recorded by MEMRI. Data were processed by region-based analysis of distinct brain structures after z-scores normalization. SD, standard deviation; L, left side; R, right side.</p

Study design.

<p>Overview on the study design for monitoring the influence of food composition on whole brain activity patterns by manganese-enhanced magnetic resonance imaging.</p