Biology subjects

Ammon, W.

Publications and source records attributed to Ammon, W..

5 recordsLinked to original sources

bioRxiv2026

The Infant Brainstem - A Multimodal Multiscale Postmortem Imaging Pipeline

Brainstem disorders in human infants - including sudden infant death syndrome (SIDS), the leading cause of postnatal infant mortality in the United States - are characterized by cellular and molecular abnormalities that conventional neuroimaging cannot detect. A substantial challenge arises from the fact that the immature myelination of the infant brain severely degrades MRI contrast, leaving the discrete nuclei and white matter tracts of the brainstem poorly resolved at the scale where pathology occurs. We introduce a postmortem imaging pipeline that bridges this gap by integrating four spatially registered modalities: whole-brain magnetic resonance imaging (MRI) (550 m), brainstem-specific MRI (150 m), polarization-sensitive optical coherence tomography (PSOCT, 10 m), and histology with immunohistochemistry (1.88 m). Our central finding is that PSOCT provides excellent tissue contrast independent of myelination state - directly overcoming the principal limitation of MRI in the infant brain -while enabling three-dimensional visualization of nuclei and tracts at resolutions 15 to 55 times finer than MRI alone. Histology provides cellular-level ground truth and validates the optical contrasts. Applied here to a normative 34-day-old infant brainstem, this pipeline establishes a generalizable framework for studying infant brainstem neuroanatomy in three dimensions, with particular relevance to disorders such as SIDS where gross anatomy is intact but cellular abnormalities remain the target of investigation.

neuroscience↗

bioRxiv2024

Imaging of developing human brains with ex vivo PSOCT and dMRI

The human brain undergoes substantial developmental changes in the first five years of life. Particularly in the white matter, myelination of axons occurs near birth and continues at a rapid pace during the first 2 to 3 years. Diffusion MRI (dMRI) has revolutionized our understanding of developmental trajectories in white matter. However, the mm-resolution of in vivo techniques bears significant limitation in revealing the microstructure of the developing brain. Polarization sensitive optical coherence tomography (PSOCT) is a three-dimensional (3D) optical imaging technique that uses polarized light interferometry to target myelinated fiber tracts with micrometer resolution. Previous studies have shown that PSOCT contributes significantly to the elucidation of myelin content and quantification of fiber orientation in adult human brains. In this study, we utilized the PSOCT technique to study developing brains during the first 5 years of life in combination with ex vivo dMRI. The results showed that the optical properties of PSOCT quantitatively reveal the myelination process in young children. The imaging contrast of the optic axis orientation is a sensitive measure of fiber orientations in largely unmyelinated brains as young as 3-months-old. The micrometer resolution of PSOCT provides substantially enriched information about complex fiber networks and complements submillimeter dMRI. This new optical tool offers great potential to reveal the white matter structures in normal neurodevelopment and developmental disorders in unprecedented detail.

neuroscience↗

bioRxiv2023

Quantitative imaging of three-dimensional fiber orientation in the human brain via two illumination angles using polarization-sensitive optical coherence tomography

The accurate measurement of three-dimensional (3D) fiber orientation in the brain is crucial for reconstructing fiber pathways and studying their involvement in neurological diseases. Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) provide important tools to directly quantify fiber orientation at micrometer resolution. However, brain imaging based on the optic axis by PS-OCT so far has been limited to two-dimensional in-plane orientation, preventing the comprehensive study of connectivity in 3D. In this work, we present a novel method to obtain the 3D fiber orientation in full angular space with only two illumination angles. We measure the optic axis orientation and the apparent birefringence by PS-OCT from a normal and a 15 deg tilted illumination, and then apply a computational method yielding the 3D optic axis orientation and true birefringence. We verify that our method accurately recovers a large range of through-plane orientations from -85 deg to 85 deg with a high angular precision. We further present 3D fiber orientation maps of entire coronal sections of human cerebrum and brainstem with 10 m in-plane resolution, revealing unprecedented details of fiber configurations. We envision that further development of our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain and other complex fibrous tissues at microscopic level.

neuroscience↗

bioRxiv2021

Refractive-index matching enhanced polarization-sensitive optical coherence tomography quantification in human brain tissue

The importance of polarization-sensitive optical coherence tomography (PS-OCT) has been increasingly recognized in human brain imaging. Despite the recent progress of PS-OCT in revealing white matter architecture and orientation, quantification of fine-scale fiber tracts in the human brain cortex has been a challenging problem, due to a low birefringence in the gray matter. In this study, we investigated the effect of refractive index matching by 2,2-thiodiethanol (TDE) immersion on the improvement of PS-OCT measurements in ex vivo human brain tissue. We obtain the cortical fiber orientation maps in the gray matter, which reveals the radial fibers in the gyrus, the U-fibers along the sulcus, as well as distinct layers of fiber axes exhibiting laminar organization. Further analysis shows that index matching reduces the noise in axis orientation measurements by 56% and 39%, in white and gray matter, respectively. Index matching also enables precise measurements of apparent birefringence, which was underestimated in the white matter by 82% but overestimated in the gray matter by 16% prior to TDE immersion. Mathematical simulations show that the improvements are primarily attributed to the reduction in the tissue scattering coefficient, leading to an enhanced signal-to-noise ratio in deeper tissue regions, which could not be achieved by conventional noise reduction methods.

bioengineering↗

bioRxiv2021

Quantification of volumetric morphometry and optical property in the cortex of human cerebellum at micrometer resolution

The surface of the human cerebellar cortex is much more tightly folded than the cerebral cortex. Volumetric analysis of cerebellar morphometry in magnetic resonance imaging studies suffers from insufficient resolution, and therefore has had limited impact on disease assessment. Automatic serial polarization-sensitive optical coherence tomography (as-PSOCT) is an emerging technique that offers the advantages of microscopic resolution and volumetric reconstruction of large-scale samples. In this study, we reconstructed multiple cubic centimeters of ex vivo human cerebellum tissue using as-PSOCT. The morphometric and optical properties of the cerebellar cortex across five subjects were quantified. While the molecular and granular layers exhibited similar mean thickness in the five subjects, the thickness varied greatly between the crown of the folium and the depth of the fissure in the granular layer within subjects. Layer-specific optical property remained homogenous within individual subjects but showed higher cross-subject variability than layer thickness. High-resolution volumetric morphometry and optical property maps of human cerebellar cortex revealed by as-PSOCT have great potential to advance our understanding of cerebellar function and diseases. HighlightsWe reconstructed cubic centimeters of human cerebellar samples at micrometer resolution in five subjects. Thickness of the granular layer varies greatly between the crowns and depths of cerebellar fissures. Cross-subject variability is higher in optical property than cortical morphology. Our results suggest homogenous cell and myelin density in the cortical layers of human cerebellum despite the highly convoluted folding patterns.

neuroscience↗