Recent advances in scanning tomographic acoustic microscopy

We present the recent developments of the Scanning Tomographic Acoustic Microscope (STAM). The STAM was proposed as a method to achieve 3D imaging capability for the Scanning Laser Acoustic Microscope (SLAM). With the addition of a quadrature receiver, the complex scattered wave field can now be detected, and consequently the STAM is capable of subsurface holographic and tomographic imaging. The resolution improvement of the STAM can be attributed directly to the detection of the phase information and the image reconstruction technique. The STAM is sensitive to phase errors in the tomographic projections. In particular, the quadrature phase error and the initial phase error in the complex projections are critical to the tomographic reconstruction process. For multiple-angle tomography, high-precision projection registration and alignment become necessary. By obtaining solutions to these implementation problems, we have succeeded in obtaining images superior to the original SLAM images. In addition, quantitative ultrasonic imaging is possible with the STAM, and a method is presented to image the velocity parameter of simple specimens. With these capabilities, the STAM may become a useful tool for high-resolution subsurface nondestructive evaluation.     

Direct Blood Cell Flow Imaging in Microvascular Networks

Blood flow dynamics in microvascular networks are intimately related to the health of tissues and organs. While numerous imaging modalities and techniques have been developed to assess blood flow dynamics for various applications, their utilization has been hampered by limited imaging speed and indirect quantification of blood flow dynamics. Here, direct blood cell flow imaging (DBFI) is demonstrated that provides visualization of individual motions of blood cells over a field of 0.71 mm × 1.42 mm with a time resolution of 0.69 ms (1450 frames s⁻¹) without using any exogenous agents. DBFI enables precise dynamic analysis of blood cell flow velocities and fluxes in various vessels over a large field, from capillaries to arteries and veins, with unprecedented time resolution. Three exemplary applications of DBFI, quantification of blood flow dynamics of 3D vascular networks, analysis of heartbeat induced blood flow dynamics, and analysis of blood flow dynamics of neurovascular coupling, illustrate the potential of this new imaging technology.     

Investigation of microstructural features in regenerating bone using micro computed tomography

We illustrate some of the uses of micro-computed tomography (micro-CT) to study tissue-engineered bone using a micro-CT facility for imaging and visualizing biomaterials in three dimensions (3-D). The micro-CT is capable of acquiring 3D X-ray CT images made up of 2000(3) voxels on specimens up to 5 cm in extent with resolutions down to 2 microm. This allows the 3-D structure of tissue-engineered materials to be imaged across orders of magnitude in resolution. This capability is used to examine an explanted, tissue-engineered bone material based on a polycaprolactone scaffold and autologous bone marrow cells. Imaging of the tissue-engineered bone at a scale of 1 cm and resolutions of 10 microm allows one to visualize the complex ingrowth of bone into the polymer scaffold. From a theoretical viewpoint the voxel data may also be used to calculate expected mechanical properties of the tissue-engineered implant. These observations illustrate the benefits of tomography over traditional techniques for the characterization of bone morphology and interconnectivity. As the method is nondestructive it can perform a complimentary role to current histomorphometric techniques.     

Backward-mode multiwavelength photoacoustic scanner using a planar Fabry-Perot polymer film ultrasound sensor for high-resolution three-dimensional imaging of biological tissues

A multiwavelength backward-mode planar photoacoustic scanner for 3D imaging of soft tissues to depths of several millimeters with a spatial resolution in the tens to hundreds of micrometers range is described. The system comprises a tunable optical parametric oscillator laser system that provides nanosecond laser pulses between 600 and 1200 nm for generating the photoacoustic signals and an optical ultrasound mapping system based upon a Fabry-Perot polymer film sensor for detecting them. The system enables photoacoustic signals to be mapped in 2D over a 50 mm diameter aperture in steps of 10 microm with an optically defined element size of 64 microm. Two sensors were used, one with a 22 microm thick polymer film spacer and the other with a 38 mum thick spacer providing -3 dB acoustic bandwidths of 39 and 22 MHz, respectively. The measured noise equivalent pressure of the 38 microm sensor was 0.21 kPa over a 20 MHz measurement bandwidth. The instrument line-spread function (LSF) was measured as a function of position and the minimum lateral and vertical LSFs found to be 38 and 15 microm, respectively. To demonstrate the ability of the system to provide high-resolution 3D images, a range of absorbing objects were imaged. Among these was a blood vessel phantom that comprised a network of blood filled tubes of diameters ranging from 62 to 300 microm immersed in an optically scattering liquid. In addition, to demonstrate the applicability of the system to spectroscopic imaging, a phantom comprising tubes filled with dyes of different spectral characteristics was imaged at a range of wavelengths. It is considered that this type of instrument may provide a practicable alternative to piezoelectric-based photoacoustic systems for high-resolution structural and functional imaging of the skin microvasculature and other superficial structures.     

Adaptive optics-optical coherence tomography: optimizing visualization of microscopic retinal structures in three dimensions

Adaptive optics-optical coherence tomography (AO-OCT) permits improved imaging of microscopic retinal structures by combining the high lateral resolution of AO with the high axial resolution of OCT, resulting in the narrowest three-dimensional (3D) point-spread function (PSF) of all in vivo retinal imaging techniques. Owing to the high volumetric resolution of AO-OCT systems, it is now possible, for the first time, to acquire images of 3D cellular structures in the living retina. Thus, with AO-OCT, those retinal structures that are not visible with AO or OCT alone (e.g., bundles of retinal nerve fiber layers, 3D mosaic of photoreceptors, 3D structure of microvasculature, and detailed structure of retinal disruptions) can be visualized. Our current AO-OCT instrumentation uses spectrometer-based Fourier-domain OCT technology and two-deformable-mirror-based AO wavefront correction. We describe image processing methods that help to remove motion artifacts observed in volumetric data, followed by innovative data visualization techniques [including two-dimensional (2D) and 3D representations]. Finally, examples of microscopic retinal structures that are acquired with the University of California Davis AO-OCT system are presented.     

Eddy current imaging,array sensors and flaw reconstruction

Eddy current imaging is widely accepted as a nondestructive testing technique enabling efficient flaw reconstruction based on much richer and comprehensive data sets than the traditional Lissajous patterns obtained from a single scan. In this paper the essential problems encountered during creation and processing of eddy current images are reviewed. The special role of eddy current transducers in creation of eddy current images is emphasized. The main part of the paper deals with formation and solving of eddy current problems which arise when flaw shapes should be reconstructed. An iterative method for reconstruction of 3D flaw images is proposed and discussed. The relation between reconstruction of the 3-D flaw image and the restoration of its 2-D top view is analysed.     

术中双功超声在7例脑少突胶质细胞瘤的应用

研究目的：探讨术中双功超声在脑少突胶质细胞瘤的应用价值。方法：回顾分析7例经病理证实的少突胶质细胞瘤的术中双功超声图像。术中超声（Intraoperative Ultrasound,IOUS）由同一检查者按照统一图像质量标准存储、分析。B模式评估病灶位置、大小、回声、边界、形态、其他征象,D模式评估病灶多普勒血流信号。结果：7例少突胶质瘤的最大径线平均值为5.2 cm,病灶边缘距脑膜<1 cm者占71.4%。85.7%为稍强回声团块,85.7%边界清晰,57.1%形态不规则,71.4%伴有不同形状的高回声,71.4% Adler血流分级为3级。结论：IOUS的B模式可用于脑少突胶质细胞瘤的实时定位及术中监测,D模式血流信息有助于定位脑部重要血管,进行术中预警。声像图中出现不同形状的高回声,后方不伴声影,提示钙化可能性大,对胶质瘤的影像学分级有一定帮助。     

Micro-CT Imaging of MEMS Components

Micro-Electromechanical Systems (MEMS) have become increasingly commonplace in varied uses such as miniature pumps, motors, and sensors. As MEMS size continues to decrease, the intricacy of their construction has increased. With this increase in complexity comes a need to evaluate the assembly and functionality of these devices in a nondestructive manner. We proposed the utilization of micro-CT imaging as a method of such evaluation for MEMS devices. Computational simulations were performed in order to determine optimal source materials and imaging parameters for micro-CT scans. Multiple MEMS components of various architecture, fabricated by Sandia National Labs, were then imaged in order to verify the simulations, as well as to prove the feasibility of micro-CT imaging of such devices. The raw data from these scans was run through computational simulations to verify the best choice of filter and interpolation method when reconstructing micro-CT images. The results of the simulations, as well as the level of detail present in the three dimensional reconstructed images of various MEMS devices proved the feasibility of micro-CT as an effective tool for the evaluation of such devices.     

血管网光声成像的机器学习抗散射仿真研究

乳腺癌已成为全球女性发病率最高的肿瘤疾病,微血管成像对乳腺癌的治疗方案和预后有重要意义。光声层析成像术(Photoacoustic Tomography, PAT)可有效对乳腺癌内微血管网进行成像,但肿瘤组织内部的异质微结构和钙化点的散射对成像质量影响较大。针对该问题,文章基于U-Net的卷积神经网络对不同颗粒散射条件下软组织中血管网图像散斑开展仿真研究。仿真结果表明,该神经网络可以学习光声散斑图像和成像目标之间的映射关系,提取出隐藏在噪声中的血管光声信号,并重建出轮廓清晰、背景清晰的高质量血管图像,表明U-Net网络可以从高度模糊的散射图像中提取出有效的光声信息,实现目标图像的高清重建,在乳腺癌的诊断成像中具有广阔的应用前景。     

Pediatric brain extraction from T2-weighted MR images using 3D dual frame U-net and human connectome database

Accurate extraction of brain tissues from magnetic resonance (MR) images is important in neuroradiology. However, brain extraction is more difficult for pediatric brains than for adult brains due to several factors including smaller brain sizes and lower tissue contrasts. In this work, we propose a brain extraction technique that utilizes dual frame (DF) 3D U-net deep learning architecture and the human connectome project (HCP) database for multislice 2D pediatric T2-weighted MR images with diseases. To improve segmentation accuracy in small pediatric brains with detailed boundary regions, DF 3D U-net architecture was used. We pretrained networks with the HCP database to compensate for the limited amount of MR images and manual segmentation masks of pediatric patients. For quantitative analysis, we compared the brain extraction results of brain extraction tool, DF, and conventional 3D U-net using the dice similarity coefficient (DSC), intersection of union (IoU), and boundary F1 (BF) scores; each deep learning architecture was evaluated with and without pretraining using the HCP. This study included 10 patients with diseases and all images were acquired using a PROPELLER MR sequence. Pretraining using the HCP database enhanced segmentation performance of the network, and the skip connections in the DF 3D U-net could enhance the contour similarity of segmentation results. Experimental results showed that the proposed method increased the DSC, IoU, and BF scores by 0.8%, 1.6%, and 1.5%, respectively, compared with those of the conventional 3D U-net without pretraining.     

Automatic image‐based stress analysis by the scaled boundary finite element method

Digital imaging technologies such as X‐ray scans and ultrasound provide a convenient and non‐invasive way to capture high‐resolution images. The colour intensity of digital images provides information on the geometrical features and material distribution which can be utilised for stress analysis. The proposed approach employs an automatic and robust algorithm to generate quadtree (2D) or octree (3D) meshes from digital images. The use of polygonal elements (2D) or polyhedral elements (3D) constructed by the scaled boundary finite element method avoids the issue of hanging nodes (mesh incompatibility) commonly encountered by finite elements on quadtree or octree meshes. The computational effort is reduced by considering the small number of cell patterns occurring in a quadtree or an octree mesh. Examples with analytical solutions in 2D and 3D are provided to show the validity of the approach. Other examples including the analysis of 2D and 3D microstructures of concrete specimens as well as of a domain containing multiple spherical holes are presented to demonstrate the versatility and the simplicity of the proposed technique. Copyright © 2016 John Wiley & Sons, Ltd.     

Micro‐vascular imaging experiences of time‐of‐flight MRA at 7T for cerebrovascular diseases

Surgical or endovascular approaches have proved effective for large‐vessel diseases over the past decade. However, approaches for small vessel diseases are unlikely to be accomplished by those for large vessels and only few have been applied, because it is hard to access to those small vessels and one could not directly delineate the affected small vessels due to a lack of detection modalities. This study is to examine patients with vascular diseases using ultra‐high field 7T MRI with conventional time‐of‐flight (TOF) sequence, 3D fast low‐angle shot (FLASH) gradient‐echo. We have evaluated several radio‐frequency (RF) coils to find the optimal one for 7T magnetic resonance angiography (MRA), especially for micro‐vascular imaging. We have conducted several comparison studies with vascular disease patients. The results showed that micro‐vessels such as lenticulostriate arteries in the subjects with risk factors like hypertension or stroke patients were significantly less than in the healthy subjects. 7T MRA images in steno‐occlusive patients also showed clearly numerous collateral vessels not visible by 1.5T or 3T MRA. Furthermore, 7T MRA images were comparable to those obtained by digital subtraction angiography (DSA), particularly for micro‐vascular imaging. In this article, we would like to share the clinical experiences on 7T MRA that vascular images of 7T MRA were superior to conventional angiography images including 1.5T and 3T MRA, and even comparable to DSA. We also expect that further technical development and clinical applications of 7T MRA would be a clinically important diagnostic tool, in terms of an early detection of the stroke in a totally non‐invasive manner. © 2014 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 24, 121–128, 2014     

Targeting orthotopic gliomas with renal-clearable luminescent gold nanoparticles

A major clinical translational challenge in nanomedicine is the potential of toxicity associated with the uptake and long-term retention of non-degradable nanoparticles (NPs) in major organs.The development of inorganic NPs that undergo renal clearance could potentially resolve this significant biosafety concern.However,it remains unclear whether inorganic NPs that can be excreted by the kidneys remain capable of targeting tumors with poor permeability.Glioblastoma multiforme,the most malignant orthotopic brain tumor,presents a unique challenge for NP delivery because of the blood-brain barrier and robust blood-tumor barrier of reactive microglia and macroglia in the tumor microenvironment.Herein,we used an orthotopic murine glioma model to investigate the passive targeting of glutathione-coated gold nanoparticles (AuNPs) of 3 nm in diameter that undergo renal clearance and 18-nm AuNPs that fail to undergo renal clearance.Remarkably, we report that 3-nm AuNPs were able to target intracranial tumor tissues with higher efficiency (2.3x relative to surrounding non-tumor normal brain tissues) and greater specificity (3.0x)than did the larger AuNPs.Pharmacokinetics studies suggested that the higher glioma targeting ability of the 3-nm AuNPs may be attributed to the longer retention time in circulation.The total accumulation of the 3-nm AuNPs in major organs was significantly less (8.4x) than that of the 18-nm AuNPs.Microscopic imaging of blood vessels and renal-clearable AuNPs showed extravasation of NPs from the leaky blood-tumor barrier into the tumor interstitium.Taken together,our results suggest that the 3-nm AuNPs,characterized by enhanced permeability and retention,are able to target brain tumors and undergo renal clearance.     

Scanning tomographic acoustic microscopy: Development and applications

The scanning tomographic acoustic microscope (STAM) is a device capable of performing subsurface imaging of microscopic specimens. Using ultrasonic energy to interrogate specimens, the STAM nondestructively obtains accurate two- and three-dimensional reconstructions of the internal structures of materials that are opaque to light. Applications include the nondestructive evaluation of integrated circuits and composite materials, characterization of the acoustical properties of substances, and examination of the condition of biological tissues. This article describes the design and development of the STAM, its capabilities, and applications using data obtained from a fully automated and integrated prototype. © 1997 John Wiley & Sons, Inc. Int J Imaging Syst Technol, 8, 255–262, 1997     

Keyhole‐3D phase contrast magnetic resonance angiography: A time‐resolved reconstruction method

In this study, we studied the keyhole imaging technique to 3D Phase‐contrast magnetic resonance angiography (PC MRA) to improve its temporal resolution. Previously, our research group has already studied the 2D PC MRA combined with keyhole technique, and evaluated the applicability. For keyhole‐3D PC MRA, the keyhole factor was used from 12.5% to 50% of the full k‐space. With keyhole factors above 50%, the images were similar to the original image and the vessels in the brain were well observed. We believe the keyhole‐3D PC MRA will give some advantages for improving the temporal resolution of MR systems.     

Partially coherent lensfree tomographic microscopy [Invited

Optical sectioning of biological specimens provides detailed volumetric information regarding their internal structure. To provide a complementary approach to existing three-dimensional (3D) microscopy modalities, we have recently demonstrated lensfree optical tomography that offers high-throughput imaging within a compact and simple platform. In this approach, in-line holograms of objects at different angles of partially coherent illumination are recorded using a digital sensor-array, which enables computing pixel super-resolved tomographic images of the specimen. This imaging modality, which forms the focus of this review, offers micrometer-scale 3D resolution over large imaging volumes of, for example, 10-15 mm(3), and can be assembled in light weight and compact architectures. Therefore, lensfree optical tomography might be particularly useful for lab-on-a-chip applications as well as for microscopy needs in resource-limited settings.     

An X-ray computed tomography imaging agent based on long-circulating bismuth sulphide nanoparticles

Nanomaterials have become increasingly important in the development of new molecular probes for in vivo imaging, both experimentally and clinically. Nanoparticulate imaging probes have included semiconductor quantum dots, magnetic and magnetofluorescent nanoparticles, gold nanoparticles and nanoshells, among others. However, the use of nanomaterials for one of the most common imaging techniques, computed tomography (CT), has remained unexplored. Current CT contrast agents are based on small iodinated molecules. They are effective in absorbing X-rays, but non-specific distribution and rapid pharmacokinetics have rather limited their microvascular and targeting performance. Here we propose the use of a polymer-coated Bi(2)S(3) nanoparticle preparation as an injectable CT imaging agent. This preparation demonstrates excellent stability at high concentrations (0.25 M Bi(3+)), high X-ray absorption (fivefold better than iodine), very long circulation times (>2 h) in vivo and an efficacy/safety profile comparable to or better than iodinated imaging agents. We show the utility of these polymer-coated Bi(2)S(3) nanoparticles for enhanced in vivo imaging of the vasculature, the liver and lymph nodes in mice. These nanoparticles and their bioconjugates are expected to become an important adjunct to in vivo imaging of molecular targets and pathological conditions.     

Atomic Spatial and Temporal Imaging of Local Structures and Light Elements inside Zeolite Frameworks

Identifying the atomic structures of porous materials in spatial and temporal dimensions by (scanning) transmission electron microscope ((S)TEM) is significant for their wide applications in catalysis, separation and energy storage. However, the sensitivity of materials to electron beams made it difficult to reduce the electron damage to specimens while maintaining the resolution and signal-to-noise ratio. It is therefore still challenging to capture multiple images of the same area in one crystal to image the temporal changes of lattices. Usings integrated differential phase contrast (iDPC) STEM, atomic-resolution imaging of beam-sensitive zeolite frameworks is achieved with an ultralow dose of 40 e⁻ Å⁻², 2–3 orders of magnitude lower than that of conventional STEM. Based on the iDPC technique, not only the atomic 3D architecture of ZSM-5 crystals but also the changes of frameworks are observed during in situ experiments. Local structures and light-element aromatics in ZSM-5 crystals can also be revealed directly under iDPC-STEM. These results provided not only an efficient tool to image beam-sensitive materials with ultralow beam current but also a new strategy to observe and investigate the hydrocarbon pools in zeolite catalysts at the single-molecule scale.     

Theoretical design of vascular imaging based on hall effect

The conceptual technique of vascular imaging and blood flow functional imaging based on Hall Effect is presented in this article. With this non‐invasive approach, both 3D anatomical imaging of the vasculature and functional imaging of blood flow in the deep structure of the human body can be obtained without radiation risk. The technique is based on the fact that the induced charges can be generated when the blood flows through the magnetic field. The induced electric field strength is measured by two groups of detector arrays, which captures not only the position of vasculature in each section, but also the velocity of blood flow and vessel size. The captured images can also be used for 3D reconstruction of the anatomical models. The designed system architecture including both hardware and software is described. © 2013 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 23, 85–96, 2013     

High-speed, two-photon scanning microscope

We have developed a high-speed two-photon microscope with submicrometer resolution in real time. The imaging speed improvement of this system is obtained by the use of a high-speed polygonal mirror scanner. The maximum achievable scanning rate is 40 mus/line, which is approximately 100 times faster than conventional scanning microscopes. High-resolution fluorescence images were recorded in real time by an intensified CCD camera. Using this instrument, we have resolved cellular architecture in three dimensions and have monitored the movements of protozoas. More important, photodamage to biological specimens during video-rate imaging can be minimized with two-photon excitation as compared with other one-photon modalities.