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Leitgeb, R.

Publications and source records attributed to Leitgeb, R..

2 recordsLinked to original sources

Bessel Beam Optical Coherence Microscopy Enables Multiscale Assessment of Cerebrovascular Network Morphology and Function

Understanding the morphology and function of large-scale cerebrovascular networks is crucial for studying brain health and disease. However, reconciling the demands for imaging on a broad scale with the precision of high-resolution volumetric microscopy has been a persistent challenge. In this study, we introduce Bessel beam optical coherence microscopy with an extended focus to capture the full cortical vascular hierarchy in mice over 1000 x 1000 x 360 m3 field-of-view at capillary level resolution. The post-processing pipeline leverages a supervised deep learning approach for precise 3D segmentation of high-resolution angiograms, hence permitting reliable examination of microvascular structures at multiple spatial scales. Coupled with high-sensitivity Doppler optical coherence tomography, our method enables the computation of both axial and transverse blood velocity components as well as vessel-specific blood flow direction, facilitating a detailed assessment of morpho-functional characteristics across all vessel dimensions. Through graph-based analysis, we deliver insights into vascular connectivity, all the way from individual capillaries to broader network interactions, a task traditionally challenging for in vivo studies. The new imaging and analysis framework extends the frontiers of research into cerebrovascular function and neurovascular pathologies.

bioengineering↗

Ultrasound-Induced Reorientation for Multi-Angle Optical Coherence Tomography

Organoid and spheroid technology have recently provided great insights into oncology, developmental biology as well as personalized medicine. Among the methods to optically monitor the structural and functional organization of such samples, optical coherence tomography (OCT) has emerged as an excellent, label-free approach. Mature organoids, however, are often too opaque for OCT due to regions of strong attenuation. This leads to severe artifacts and reduced morphological tissue information in the reconstruction, since the far-side of the specimen is not reachable. Access to multi-angle views of OCT is therefore highly desirable. This aligns with another problem affecting certain goals of organoid research: The sample needs to be embedded in a growth scaffold such as Matrigel, whereas freely floating objects would not suffer from confinement and be more easily accessible for mechanical or chemical probing. Here we present ULTrasound-Induced reorientation for Multi-Angle-OCT (ULTIMA-OCT), a solution overcoming these limitations. By inserting a small 3D-printed acoustic trap to a spectral-domain OCT system, acoustic actuation enables contact-free levitation and finely tunable stepwise reorientation of samples such as zebrafish larvae and tumor spheroids, in a controlled and reproducible manner. This enables tomographic reconstruction of (sub-)mm samples with enhanced penetration depth and reduced attenuation artifacts, by means of a model-based algorithm we developed. We show that this approach is able to fuse the diverse multi-angle OCT volumes for a joint recovery of 3D-reconstruction of reflectivity, attenuation, refractive index and position registration for zebrafish larvae. We believe that our approach represents a powerful enabling tool for developmental biology and organoid research.

bioengineering↗