Biology subjects

Herrler, A.

Publications and source records attributed to Herrler, A..

5 recordsLinked to original sources

bioRxiv2026

Light-sheet fluorescence microscopy of optically cleared human head-and-neck organs: three-dimensional tissue assessment and histological correlation

Conventional histology provides detailed cellular information but only a partial view of the three-dimensional (3D) organisation of head-and-neck tissues. We investigated whether optical tissue clearing combined with light-sheet fluorescence microscopy (LSFM) could visualise the microanatomy of large head-and-neck specimens and relate volumetric features to conventional histology. Non-neoplastic human palatine tonsil, cervical lymph node, tongue and parotid gland specimens were cleared with a solvent-based protocol, labelled with small-molecule dyes and imaged by LSFM, with haematoxylin and eosin (H&E) histology as a morphological reference. LSFM visualised the characteristic architecture of each tissue, including lymphoid follicles and crypt epithelium in tonsil, cortex, paracortex and follicles in lymph node, epithelium and intrinsic muscle fibres in tongue, and lobules, ducts and adipocytes in parotid. Following structures through successive optical sections revealed their continuity and branching over long distances, information not available from single sections. Tongue epithelial measurements were comparable with H&E, and segmentation enabled volumetric quantification of structures such as the tongue epithelium and parotid adipocytes. Optical clearing and LSFM thus provide a feasible single workflow for volumetric investigation of human head-and-neck microanatomy. These data establish a 3D morphological reference with potential applications in cancer research and staging, computational image analysis and anatomical education, to be further developed through larger donor cohorts and specific labelling.

pathology↗

bioRxiv2026

Giving you five: A neuroimaging atlas of the nigrosomes in the substantia nigra based on 3D histology

Nigrosomes are formed by clusters of pigmented dopaminergic cells in the substantia nigra that critically contribute to dopaminergic function. The ever-increasing resolution of ultra-high-field MRI brings clinical imaging of these clusters into reach, promising unprecedented insight into the functional role of the nigrosomes and their early degeneration in Parkinsons disease. However, due to the nigrosomes small extents and intricate shapes, they are not included in current MRI brain atlases, preventing nigrosome-specific MRI data analysis. We provide a comprehensive 3D histological atlas of the five nigrosomes co-aligned to the widely-used MNI152 2009b space. This atlas is based on 3D-reconstructed, ultra-high-resolution block-face images and gold-standard nigrosome delineations in calbindin-D28K immunohistochemistry. We validated the atlass accuracy using the multimodal ultra-high-resolution post mortem BigBrain dataset and demonstrated its consistency with qualitative nigrosome atlases based on classical 2D histology. We provide detailed usage instructions for applying our atlas to ultra-high-resolution and -field MRI data. The openly available atlas enables neuroimaging studies of the nigrosomes, opening a new avenue toward understanding the differential involvement of the nigrosomes in the healthy and diseased brain and the development of neuroimaging biomarkers of dopaminergic neurodegeneration.

neuroscience↗

bioRxiv2024

Investigating microscopic angioarchitecture in the human visual cortex in 3D with angioMASH tissue clearing and labelling

Non-invasive imaging techniques, such as ultra-high field fMRI, are intricately connected to the underlying vasculature and are approaching ever higher resolutions. For the analysis of fMRI signals over cortical depth at such high resolutions, microvascular differences might have to be taken into account. Therefore, a better understanding of the laminar distribution and interareal differences in the cortical vasculature is becoming more important. However, in comparison to cyto- and myeloarchitecture, the study of angioarchitecture has received far less attention and relatively few methods have been described to visualise the vascular network in the human brain. Here we present angioMASH, a method for double labelling angioarchitecture and cytoarchitecture in archival human brain tissue, based on the recently published MASH protocol. The double labelling and optical clearing of thick human brain slices can be accomplished within 16 days. We use this method to acquire multi-resolution 3D datasets of combined cyto- and angioarchitecture in large ([~]30 mm x 10 mm x 3 mm) volumes of human samples covering visual areas V1 and V2. We demonstrate for the first time, that classical angioarchitectonic features can be visualised in the human cortex and in 3D using tissue clearing and light-sheet microscopy. Lastly, we show differences in the vessel density and orientation over cortical depth within and between the two areas. Especially in V1, the vascular density is not homogeneous over cortical depth but shows distinct layering. These layers are also determined by changes in the orientation of the blood vessels from a predominantly radial to a more tangential distribution. In V2, differences in vascular density are less pronounced, but orientation profiles follow a similar trend over cortical depth. We discuss potential consequences of these differences for the interpretation of non-invasive functional imaging modalities such as fMRI or fNIRS. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=155 SRC="FIGDIR/small/609648v2_ufig1.gif" ALT="Figure 1"> View larger version (57K): org.highwire.dtl.DTLVardef@f9f841org.highwire.dtl.DTLVardef@1197e29org.highwire.dtl.DTLVardef@a9c9ccorg.highwire.dtl.DTLVardef@ffaefe_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Efficient 3D light-sheet imaging of very large-scale optically cleared human brain and prostate tissue samples.

The ability to image human tissue samples in 3D, with both cellular resolution and a large field of view (FOVs), can improve fundamental and clinical investigations. Here, we demonstrate the feasibility of light-sheet imaging of [~]5 cm3 sized formalin fixed human brain and up to [~]7 cm3 sized formalin fixed paraffin embedded (FFPE) prostate cancer samples, processed with the FFPE-MASH protocol. We present a light-sheet microscopy prototype, the cleared-tissue dual view Selective Plane Illumination Microscope (ct-dSPIM), capable of fast, 3D high-resolution acquisitions, of cubic centimetre sized cleared tissue. We used Mosaic scans for fast 3D overview scans of entire tissue samples or higher resolution overviews of large ROIs with various speeds: a) Mosaic 16 (16.4 {micro}m isotropic resolution, [~] 1.7 hr/cm3), b) Mosaic 4 (4.1 {micro}m isotropic resolution, [~] 5 hr/cm3) and c) Mosaic 0.5 (0.5 {micro}m near isotropic resolution, [~]15.8 hr/cm3). We could visualise ROIs around the border of human brain area V1/V2, and could demonstrate suitable imaging quality for Gleason score grading in prostate cancer samples. We show that ct-dSPIM imaging is an excellent technique to quantitatively assess entire MASH prepared large-scale human tissue samples in 3D, with considerable future clinical potential in prostate cancer.

neuroscience↗

bioRxiv2018

Scalable cytoarchitectonic characterization of large intact human neocortex samples

We describe MASH (Multiscale Architectonic Staining of Human cortex): a simple, fast and low-cost cytoarchitectonic labeling and optical clearing approach for human cortex samples, which can be applied to large formalin fixed adult brain samples. A suite of small-molecule fluorescent nuclear and cytoplasmic dyes in combination with new refractive index matching solutions allows deep volume imaging. This enables highly scalable human neocortical cytoarchitecture characterization with a large 3D scope.

neuroscience↗