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Mammalian neurons operate at length scales spanning six orders of magnitude; they project millimeters to centimeters across brain regions, are composed of micrometer-scale-diameter myelinated axons, and ultimately form nanometer scale synapses. Capturing these anatomical features across that breadth of scale has required imaging samples with multiple independent imaging modalities. Translating between the different modalities, however, requires imaging the same brain with each. Here, we imaged the same postmortem mouse brain over five orders of spatial resolution using MRI, whole brain micrometer-scale synchrotron x-ray tomography (μCT), and large volume automated serial electron microscopy. Using this pipeline, we can track individual myelinated axons previously relegated to axon bundles in diffusion tensor MRI or arbitrarily trace neurons and their processes brain-wide and identify individual synapses on them. This pipeline provides both an unprecedented look across a single brain's multi-scaled organization as well as a vehicle for studying the brain's multi-scale pathologies.

The technique of remote focusing (RF) has attracted considerable attention among microscopists due to its ability to quickly adjust focus across different planes, thus facilitating quicker volumetric imaging. However, the difficulty in changing objectives to align with a matching objective in a remote setting while upholding key requirements remains a challenge. We aim to propose a customized yet straightforward technique to align multiple objectives with a remote objective, employing an identical set of optical elements to ensure meeting the criteria of remote focusing. We propose a simple optical approach for aligning multiple objectives with a singular remote objective to achieve a perfect imaging system. This method utilizes readily accessible, commercial optical components to meet the fundamental requirements of remote focusing. Our experimental observations indicate that the proposed RF technique offers at least comparable, if not superior, performance over a significant axial depth compared with the conventional RF technique based on commercial lenses while offering the flexibility to switch the objective for multi-scale imaging. The proposed technique addresses various microscopy challenges, particularly in the realm of multi-resolution imaging. We have experimentally demonstrated the efficacy of this technique by capturing images of focal volumes generated by two distinct objectives in a water medium.

Whole-brain imaging has become an increasingly important approach to investigate neural structures, such as somata distribution, dendritic morphology, and axonal projection patterns. Different structures require whole-brain imaging at different resolutions. Thus, it is highly desirable to perform whole-brain imaging at multiple scales. Imaging a complete mammalian brain at synaptic resolution is especially challenging, as it requires continuous imaging from days to weeks because of the large number of voxels to sample, and it is difficult to acquire a constant quality of imaging because of light scattering during in toto imaging. Here, we reveal that light-sheet microscopy has a unique advantage over wide-field microscopy in multi-scale imaging because of its decoupling of illumination and detection. Based on this observation, we have developed a multi-scale light-sheet microscope that combines tiling of light-sheet, automatic zooming, periodic sectioning, and tissue expansion to achieve a constant quality of brain-wide imaging from cellular (3 μm × 3 μm × 8 μm) to sub-micron (0.3 μm × 0.3 μm × 1 μm) spatial resolution rapidly (all within a few hours). We demonstrated the strength of the system by testing it using mouse brains prepared using different clearing approaches. We were able to track electrode tracks as well as axonal projections at sub-micron resolution to trace the full morphology of single medial prefrontal cortex (mPFC) neurons that have remarkable diversity in long-range projections.

This article comments on: Staedler YM, Kreisberger T, Manafzadeh S, Chartier M, Handschuh S, Pamperl S, Sontag S, Paun O, Schönenberger J. 2017. Novel computed tomography-based tools reliably quantify plant reproductive investment. Journal of Experimental Botany 69, 525-535.

Shale is a highly heterogeneous material across multiple scales. A typical shale consists of nanometer-scale pores and minerals mixed with macroscale fractures and particles of varying size. High-resolution imaging is crucial for characterizing the composition and microstructure of this rock. However, it is generally not feasible to image a large sample of shale at a high resolution over a large field of view (FOV), thus limiting a full characterization of the microstructure of this material. We present a stochastic framework based on multiple-point statistics that uses high-resolution training images to enhance low-resolution images obtained over a large FOV. We demonstrate the approach using X-ray micro-tomography images of organic-rich Woodford shale obtained at two different resolutions and FOV. Results show that the proposed technique can generate realistic high-resolution images of the microstructure of shale over a large FOV.

Ting Qiu,1,* Yintao Lan,1,* Zuwu Wei,2 Yanfen Zhang,3 Yanping Lin,1 Chenggong Tu,1 Guangjuan Mao,1 Lingmin Zhang,3 Bin Yang,1 Jian Zhang1 1The Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Department of Biomedical Engineering, School of Basic Medical Sciences, Guangzhou Medical University, Guangzhou, 511436, People's Republic of China; 2The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, 350025, People's Republic of China; 3School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, 511436, Guangdong, People's Republic of China*These authors contributed equally to this workCorrespondence: Jian Zhang Email jianzhang@gzhmu.edu.cnBackground: Effective treatment strategy for cervical carcinoma is subject to the limitation of its anatomical location and histological characteristics. Comprehensive imaging before cervical carcinoma treatment is of great significance for the patients. Current imaging methods cannot meet the requirements of high resolution, deep imaging depth and non-invasive imaging at the same time. Fortunately, Photoacoustic imaging (PAI) is a novel imaging method that combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. Moreover, PAI-guided photothermal therapy (PTT) by aid of targeting nanoparticles is an emerging and effective cancer treatment in recent years.Methods: Here, strong near-infrared region (NIR) absorption-conjugated polymer PIIGDTS (PD) nanoparticles with folic acid (FA) modification (namely, PD-FA) that targeted at Hela cell were specifically designed as cervical tumor imaging contrast agents and photothermal agents.Results: The obtained PD-FAnanoparticles exhibited admirable photoacoustic contrast-enhancing ability and desirable PTT behavior with the photothermal conversion efficiency as high as 62.6% in vitro. Furthermore, the PAI performance and PTT efficiency were tested in HeLa tumor-bearing nude mice after injection of PD-FA nanoparticles. In vivo multi-scale, PAI provided B-san and 3D dimension imaging for intuitive and comprehensive information of Hela tumor. Moreover, the Hela tumor can be completely eliminated within 18 days after PTT, with no toxicity and side effects.Conclusion: In summary, PD-FA injection combined with PAI and PTT systems provides a novel powerful tool for early diagnosis and precise treatment of cervical cancer.Keywords: cervical cancer, multi-scale photoacoustic imaging, photothermal therapy, PIIGDTS nanoparticle

A major challenge in neuroscience is how to study structural alterations in the brain. Even small changes in synaptic composition could have severe outcomes for body functions. Many neuropathological diseases are attributable to disorganization of particular synaptic proteins. Yet, to detect and comprehensively describe and evaluate such often rather subtle deviations from the normal physiological status in a detailed and quantitative manner is very challenging. Here, we have compared side-by-side several commercially available light microscopes for their suitability in visualizing synaptic components in larger parts of the brain at low resolution, at extended resolution as well as at super-resolution. Microscopic technologies included stereo, widefield, deconvolution, confocal, and super-resolution set-ups. We also analyzed the impact of adaptive optics, a motorized objective correction collar and CUDA graphics card technology on imaging quality and acquisition speed. Our observations evaluate a basic set of techniques, which allow for multi-color brain imaging from centimeter to nanometer scales. The comparative multi-modal strategy we established can be used as a guide for researchers to select the most appropriate light microscopy method in addressing specific questions in brain research, and we also give insights into recent developments such as optical aberration corrections.

Effective treatment strategy for cervical carcinoma is subject to the limitation of its anatomical location and histological characteristics. Comprehensive imaging before cervical carcinoma treatment is of great significance for the patients. Current imaging methods cannot meet the requirements of high resolution, deep imaging depth and non-invasive imaging at the same time. Fortunately, Photoacoustic imaging (PAI) is a novel imaging method that combines rich optical contrast, high ultrasonic spatial resolution, and deep penetration depth in a single modality. Moreover, PAI-guided photothermal therapy (PTT) by aid of targeting nanoparticles is an emerging and effective cancer treatment in recent years. Here, strong near-infrared region (NIR) absorption-conjugated polymer PIIGDTS (PD) nanoparticles with folic acid (FA) modification (namely, PD-FA) that targeted at Hela cell were specifically designed as cervical tumor imaging contrast agents and photothermal agents. The obtained PD-FA nanoparticles exhibited admirable photoacoustic contrast-enhancing ability and desirable PTT behavior with the photothermal conversion efficiency as high as 62.6% in vitro. Furthermore, the PAI performance and PTT efficiency were tested in HeLa tumor-bearing nude mice after injection of PD-FA nanoparticles. In vivo multi-scale, PAI provided B-san and 3D dimension imaging for intuitive and comprehensive information of Hela tumor. Moreover, the Hela tumor can be completely eliminated within 18 days after PTT, with no toxicity and side effects. In summary, PD-FA injection combined with PAI and PTT systems provides a novel powerful tool for early diagnosis and precise treatment of cervical cancer.

Shale is a highly heterogeneous material across multiple scales. A typical shale consists of nanometer-scale pores and minerals mixed with macro-scale fractures and particles of varying size. High-resolution imaging is crucial for characterizing the composition and microstructure of this rock. Yet, it is generally not feasible to image a large sample of shale at a high resolution over a large field of view (FOV), thus limiting a full characterization of the microstructure of this material. We present a stochastic framework based on multiple-point statistics that uses high-resolution training images to enhance low-resolution images obtained over a large FOV. Here, we demonstrate the approach using X-ray micro-tomography images of organic-rich Woodford shale obtained at two different resolutions and FOV. Results show that the proposed technique can generate realistic high-resolution images of the microstructure of shale over a large FOV.

In this paper, we propose a new ground penetrating radar (GPR) imaging technique based on multi-scale weighted back projection (BP) processing. Firstly, the whole imaging region is discretized by large scale and low-resolution imaging result is obtained by using traditional BP imaging technique. Secondly, the potential targets regions (PTR) are delineated from low-resolution imaging result by using intensity detection method. In the PTR, small scale discretization is implemented and higher resolution imaging result is obtained by using weighted BP imaging technique. A weight factor is designed by analyzing the statistical characteristics of scattering data on the time-delay curve. The above “discretization-imaging-PTR delineation” processing continues until the imaging resolution reaches the specified requirement. In the multi-scale imaging result, the resolution in other regions is not as high as that in PTR. This algorithm can get higher resolution imaging results with much lower computation compared with traditional BP imaging algorithm. The simulation of this algorithm is processed and experimental results validate the feasibility of this method.