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 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.

Quantitative optical coherence microscopy of neuron morphology in human entorhinal cortex.

Introduction: The size and shape of neurons are important features indicating aging and the pathology of neurodegenerative diseases. Despite the significant advances of optical microscopy, quantitative analysis of the neuronal features in the human brain remains largely incomplete. Traditional histology on thin slices bears tremendous distortions in three-dimensional reconstruction, the magnitude of which are often greater than the structure of interest. Recently development of tissue clearing techniques enable the whole brain to be analyzed in small animals; however, the application in the human remains challenging. Methods: In this study, we present a label-free quantitative optical coherence microscopy (OCM) technique to obtain the morphological parameters of neurons in human entorhinal cortex (EC). OCM uses the intrinsic back-scattering property of tissue to identify individual neurons in 3D. The area, length, width, and orientation of individual neurons are quantified and compared between layer II and III in EC. Results: The high-resolution mapping of neuron size, shape, and orientation shows significant differences between layer II and III neurons in EC. The results are validated by standard Nissl staining of the same samples. Discussion: The quantitative OCM technique in our study offers a new solution to analyze variety of neurons and their organizations in the human brain, which opens new insights in advancing our understanding of neurodegenerative diseases.

Longitudinal changes in auditory and reward systems following receptive music-based intervention in older adults.

Listening to pleasurable music is known to engage the brain's reward system. This has motivated many cognitive-behavioral interventions for healthy aging, but little is known about the effects of music-based intervention (MBI) on activity and connectivity of the brain's auditory and reward systems. Here we show preliminary evidence that brain network connectivity can change after receptive MBI in cognitively unimpaired older adults. Using a combination of whole-brain regression, seed-based connectivity analysis, and representational similarity analysis (RSA), we examined fMRI responses during music listening in older adults before and after an 8-week personalized MBI. Participants rated self-selected and researcher-selected musical excerpts on liking and familiarity. Parametric effects of liking, familiarity, and selection showed simultaneous activation in auditory, reward, and default mode network (DMN) areas. Functional connectivity within and between auditory and reward networks was modulated by participant liking and familiarity ratings. RSA showed significant representations of selection and novelty at both time-points, and an increase in striatal representation of musical stimuli following intervention. An exploratory seed-based connectivity analysis comparing pre- and post-intervention showed significant increase in functional connectivity between auditory regions and medial prefrontal cortex (mPFC). Taken together, results show how regular music listening can provide an auditory channel towards the mPFC, thus offering a potential neural mechanism for MBI supporting healthy aging.