RESUMEN
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. Comprehensive reconstruction of axonal tracts and small fascicles requires high-resolution technology beyond the ability of current in vivo imaging (e.g. diffusion magnetic resonance imaging). Optical imaging methods such as polarization-sensitive optical coherence tomography (PS-OCT) and polarization microscopy can quantify fiber orientation at micrometer resolution but have been limited to two-dimensional in-plane orientation or thin slices, preventing the comprehensive study of connectivity in 3D. In this work we present a novel method to quantify volumetric 3D orientation in full angular space with PS-OCT. We measure the polarization contrasts of the brain sample from two illumination angles of 0 and 15 degrees and apply a computational method that yields the 3D optic axis orientation and true birefringence. We further present 3D fiber orientation maps of entire coronal cerebrum sections and brainstem with 10 µm in-plane resolution, revealing unprecedented details of fiber configurations. We envision that our method will open a promising avenue towards large-scale 3D fiber axis mapping in the human brain as well as other complex fibrous tissues at microscopic level.
RESUMEN
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.
RESUMEN
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 µm 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.
RESUMEN
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 show that we can obtain fiber orientation maps of U-fibers that underlie sulci, as well as cortical fibers in the gray matter, including radial fibers in gyri and distinct layers of fibers 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.
RESUMEN
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 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.
