Scalable mapping of myelin and neuron density in the human brain with micrometer resolution

Optical coherence tomography (OCT) is an emerging 3D imaging technique that allows quantification of intrinsic optical properties such as scattering coefficient and back-scattering coefficient, and has proved useful in distinguishing delicate microstructures in the human brain. The origins of scattering in brain tissues are contributed by the myelin content, neuron size and density primarily; however, no quantitative relationships between them have been reported, which hampers the use of OCT in fundamental studies of architectonic areas in the human brain and the pathological evaluations of diseases. Here, we built a generalized linear model based on Mie scattering theory that quantitatively links tissue scattering to myelin content and neuron density in the human brain. We report a strong linear relationship between scattering coefficient and the myelin content that is retained across different regions of the brain. Neuronal cell body turns out to be a secondary contribution to the overall scattering. The optical property of OCT provides a label-free solution for quantifying volumetric myelin content and neuron cells in the human brain.

Deep tissue scattering compensation with three-photon F-SHARP

Optical imaging techniques are widely used in biological research, but their penetration depth is limited by tissue scattering. Wavefront shaping techniques are able to overcome this problem in principle, but are often slow and their performance depends on the sample. This greatly reduces their practicability for biological applications. Here we present a scattering compensation technique based on three-photon (3P) excitation, which converges faster than comparable two-photon (2P) techniques and works reliably even on densely labeled samples, where 2P approaches fail. To demonstrate its usability and advantages for biomedical imaging we apply it to the imaging of dendritic spines on GFP-labeled layer 5 neurons in an anesthetized mouse.

Volumetric super-resolution imaging by serial ultrasectioning and STochastic Optical Reconstruction Microscopy (STORM) in neural tissue

Here we present a protocol for collecting large-volume, four-color, single-molecule localization imaging data from neural tissue. We have applied this technique to map the location and identities of chemical synapses across whole cells in mouse retinae. Our sample preparation approach improves 3D STORM image quality by reducing tissue scattering, photobleaching, and optical distortions associated with deep imaging. This approach can be extended for use on other tissue types enabling life scientists to perform volumetric super-resolution imaging in diverse biological models. For a detailed application of this protocol, please refer to Sigal et al., 2015.

Recent Progress on NIR-II Photothermal Therapy

Photothermal therapy is a very promising treatment method in the field of cancer therapy. The photothermal nanomaterials in near-infrared region (NIR-I, 750-900 nm) attracts extensive attention in recent years because of the good biological penetration of NIR light. However, the penetration depth is still not enough for solid tumors due to high tissue scattering. The light in the second near-infrared region (NIR-II, 1000-1700 nm) allows deeper tissue penetration, higher upper limit of radiation and greater tissue tolerance than that in the NIR-I, and it shows greater application potential in photothermal conversion. This review summarizes the photothermal properties of Au nanomaterials, two-dimensional materials, metal oxide sulfides and polymers in the NIR-II and their application prospects in photothermal therapy. It will arouse the interest of scientists in the field of cancer treatment as well as nanomedicine.

New Insights into High Frequency Ultrasonic Tissue Scattering

New Insights into High Frequency Ultrasonic Tissue Scattering

New Insights into High Frequency Ultrasonic Tissue Scattering

New Insights into High Frequency Ultrasonic Tissue Scattering

Scalable mapping of myelin and neuron density in the human brain with micrometer resolution

Optical Coherence Tomography (OCT) is an emerging 3D imaging technique that allows quantification of intrinsic optical properties such as scattering coefficient and back-scattering coefficient, and has proved useful in distinguishing delicate microstructures in the human brain. The origins of scattering in brain tissues are contributed by the myelin content, neuron size and density primarily; however, no quantitative relationships between them have been reported, which hampers the use of OCT in fundamental studies of architectonic areas in the human brain and the pathological evaluations of diseases. To date, histology remains the golden standard, which is prone to errors and can only work on a small number of subjects. Here, we demonstrate a novel method that uses serial sectioning OCT to quantitatively measure myelin content and neuron density in the human brain. We found that the scattering coefficient possesses a strong linear relationship with the myelin content across different regions of the human brain, while the neuron density serves as a secondary contribution that only slightly modulates the overall tissue scattering.

High-resolution structural and functional deep brain imaging using adaptive optics three-photon microscopy

Multi-photon microscopy has become a powerful tool to visualize the morphology and function of neural cells and circuits in the intact mammalian brain. Yet, tissue scattering, optical aberrations, and motion artifacts degrade the achievable image quality with depth. Here we developed a minimally invasive intravital imaging methodology by combining three-photon excitation, indirect adaptive optics correction, and active electrocardiogram gating to achieve near-diffraction limited resolution up to a depth of 1.2mm in the mouse brain. We demonstrate near-diffraction-limited imaging of deep cortical and sub-cortical dendrites and spines as well as of calcium transients in deep-layer astrocytes in vivo.