Biomedical Imaging Technique Research Articles

Tissue Acoustoelectric Effect Modeling From Solid Mechanics Theory.

The acoustoelectric (AE) effect is a basic physical phenomenon, which underlies the changes made in the conductivity of a medium by the application of focused ultrasound. Recently, based on the AE effect, several biomedical imaging techniques have been widely studied, such as ultrasound-modulated electrical impedance tomography and ultrasound current source density imaging. To further investigate the mechanism of the AE effect in tissue and to provide guidance for such techniques, we have modeled the tissue AE effect using the theory of solid mechanics. Both bulk compression and thermal expansion of tissue are considered and discussed. Computation simulation shows that the muscle AE effect result, conductivity change rate, is 3.26×10-3 with 4.3-MPa peak pressure, satisfying the theoretical value. Bulk compression plays the main role for muscle AE effect, while thermal expansion makes almost no contribution to it. In addition, the AE signals of porcine muscle are measured at different focal positions. With the same magnitude order and the same change trend, the experiment result confirms that the simulation result is effective. Both simulation and experimental results validate that tissue AE effect modeling using solid mechanics theory is feasible, which is of significance for the further development of related biomedical imaging techniques.

The effect of imatinib therapy on tumour cycling hypoxia, tissue oxygenation and vascular reactivity

Background: Several biomedical imaging techniques have recently been developed to probe hypoxia in tumours, including oxygen-enhanced (OE) and blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI). These techniques have strong potential for measuring both chronic and transient (cycling) changes in hypoxia, and to assess response to vascular-targeting therapies in the clinic. Methods: In this study, we investigated the use of BOLD and OE-MRI to assess changes in cycling hypoxia, tissue oxygenation and vascular reactivity to hyperoxic gas challenges, in mouse models of colorectal therapy, following treatment with the PDGF-receptor inhibitor, imatinib mesylate (Glivec). Results: Whilst no changes were observed in imaging biomarkers of cycling hypoxia (from BOLD) or chronic hypoxia (from OE-MRI), the BOLD response to carbogen-breathing became significantly more positive in some tumour regions and more negative in other regions, thereby increasing overall heterogeneity. Conclusions: Imatinib did not affect the magnitude of cycling hypoxia or OE-MRI signal, but increased the heterogeneity of the spatial distribution of BOLD MRI changes in response to gas challenges.

The Development of Contrast Agents for Photoacoustic Molecular Imaging

Au Photoacoustic molecular imaging (PAI) is a novel biomedical imaging technique that utilize ultrasonic signal as an information carrier. PAI provides optical absorption and dielectric properties relevanted physiology and pathology at the cellular and molecular level through the use of exogenous contrast agents. These contrast agents can generate strong photoacoustic (PA) signal and provide contrast enhancement. In addition, they can be conjugated with molecular probes for targeted early detection and treatment of cancers. Here we review the new exogenous contrast agents in recent years from five types, including dyes, plasmonic nanostructure, various new class nanoparticles and multimodality contrast agents. At last we conduct a further outlook of the application prospects in the field of biomedicine.

Emission enhancement through Nd3+-Yb3+ energy transfer in multifunctional NaGdF4 nanocrystals.

The growing need for biomedical contrast agents has led to the current development of multi-functional materials such as lanthanide-based nanoparticles (NPs). The optical and magnetic properties these nanoparticles (NPs) possess are important to enhance current biomedical imaging techniques. To increase the optical emissions of the nanoparticles, neodymium (Nd3+) and ytterbium (Yb3+) were introduced into a magnetic host of NaGdF4. The energy transfer between Nd3+ and the Yb3+ was then investigated at multiple concentrations to determine the optimal dopant levels. The NaGdF4:Nd3+,Yb3+ nanoparticles were synthesized through a modified solvothermal method, resulting in rectangular structures, with an average side length of 17.87 ± 4.38 nm. A double dopant concentration of 10% Nd3+ and 4% Yb3+ was found to be optimal, increasing the emission intensity by 71.5% when compared to the widely used Nd3+ single dopant. Decay measurements confirm energy transfer from Nd3+ to Yb3+, with a lifetime shortening from Nd3+ 1064 nm emission and a calculated lifetime of 12.72 ms with 98% efficiency. Despite NaGdF4:Nd3+,Yb3+ NPs showing a slight decrease in their magnetic response at the expense of optimizing optical emission, as it is directly dependent on the Gd3+ concentration, a strong paramagnetic behavior was still observed. These results corroborate that NaGdF4:Nd3+,Yb3+ NPs are viable candidates for multimodal imaging.

Synthesis and Investigation of Structural and Optical Properties of Eu3+ Doped CaZrO3 Phosphor

The rare earth doped ceramic nanophosphors are emerging as the first priority for future display applications, radiation dosimetry and biomedical imaging techniques due to their meliorated luminescent properties. With addition of rare earth element as external impurities leads to enhancement of optical properties of phosphors. The nanocrystalline phosphor of calcium Zirconate (CaZrO3) doped with Eu3+ and co doped with Tb3+ was synthesized using the solid-state reaction method. The prepared samples are characterized by XRD, SEM and EDX clearly indicates the purity and homogeneity of the samples. The FTIR clearly indicates the enhanced absorption and transmittance characteristics. The photoluminescent studies of the prepared samples has been reported showing it as a promising constituent for future display application.

Automated detection of glaucoma using structural and non structural features.

Glaucoma is a chronic disease often called “silent thief of sight” as it has no symptoms and if not detected at an early stage it may cause permanent blindness. Glaucoma progression precedes some structural changes in the retina which aid ophthalmologists to detect glaucoma at an early stage and stop its progression. Fundoscopy is among one of the biomedical imaging techniques to analyze the internal structure of retina. Our proposed technique provides a novel algorithm to detect glaucoma from digital fundus image using a hybrid feature set. This paper proposes a novel combination of structural (cup to disc ratio) and non-structural (texture and intensity) features to improve the accuracy of automated diagnosis of glaucoma. The proposed method introduces a suspect class in automated diagnosis in case of any conflict in decision from structural and non-structural features. The evaluation of proposed algorithm is performed using a local database containing fundus images from 100 patients. This system is designed to refer glaucoma cases from rural areas to specialists and the motivation behind introducing suspect class is to ensure high sensitivity of proposed system. The average sensitivity and specificity of proposed system are 100 and 87 % respectively.

Light sheet luminescence imaging with Cherenkov excitation in thick scattering media.

Light scattering leads to a severe loss of axial and transverse resolution with depth into tissue, limiting accuracy and value of biomedical luminescence imaging techniques. High-resolution imaging beyond a few-millimeter depth is prohibited because diffusive transport dominates beyond a few scattering distances. In this study, light sheet imaging through scattering media is demonstrated using a radiotherapy linear accelerator to deliver well-defined thin scanned sheets of x-rays. These sheets produce Cherenkov light within the medium, which in turn excites luminescence of an optical probe across the sheet plane. This luminescence can then be imaged by an intensified camera positioned perpendicular to the sheet plane. The precise knowledge of the light sheet position within the medium allowed for efficient attenuation correction of the signal with depth as well as spatial deconvolution of the excitation light. Together these methods allowed for the first time, to the best of our knowledge, high-resolution imaging of tissue-equivalent phantoms up to 3 cm thick, yielding the precise position and shape of luminescent lesions located deep in tissue without the need for nonlinear image reconstruction.

Prolonged Dye Release from Mesoporous Silica-Based Imaging Probes Facilitates Long-Term Optical Tracking of Cell Populations In Vivo.

Nanomedicine is gaining ground worldwide in therapy and diagnostics. Novel nanoscopic imaging probes serve as imaging tools for studying dynamic biological processes in vitro and in vivo. To allow detectability in the physiological environment, the nanostructure-based probes need to be either inherently detectable by biomedical imaging techniques, or serve as carriers for existing imaging agents. In this study, the potential of mesoporous silica nanoparticles carrying commercially available fluorochromes as self-regenerating cell labels for long-term cellular tracking is investigated. The particle surface is organically modified for enhanced cellular uptake, the fluorescence intensity of labeled cells is followed over time both in vitro and in vivo. The particles are not exocytosed and particles which escaped cells due to cell injury or death are degraded and no labeling of nontargeted cell populations are observed. The labeling efficiency is significantly improved as compared to that of quantum dots of similar emission wavelength. Labeled human breast cancer cells are xenotransplanted in nude mice, and the fluorescent cells can be detected in vivo for a period of 1 month. Moreover, ex vivo analysis reveals fluorescently labeled metastatic colonies in lymph node and rib, highlighting the capability of the developed probes for tracking of metastasis.

Mathematical problems of joint reconstruction for biomedical multi-modality imaging techniques

Biomedical imaging aims at visualizing structural or functional information necessary for biological research or clinical diagnosis. Mathematics has played a significant role in biomedical imaging technology. A class of mathematical problems in biomedical imaging techniques is to reconstruct the information of interest from measured data, which typically poses an ill-posed inverse problem. One recent development is the multi-modality imaging technique for enriching image information by fusing multiple imaging modalities. In contrast to the existing single-mode imaging technology, there is a variety of strategies for image reconstruction of multi-modality imaging techniques. A new direction is the use of the similarity of multi-modality images, or more exactly, the use of the partial similarity of image features from different modality images for achieving the joint reconstruction of multi-modality images. The advantages of joint reconstruction are to utilize the data from different modalities to steer the reconstruction of one modality through the complementary feature information from another modality and to get better quality images. This note is a review of mathematical problems of the joint reconstruction for multi-modality imaging techniques. We introduce the key mathematical problems and report relevant progresses in this field. The fundamental Mumford-Shah functional in this approach has been discoursed in a book by Zhang Gongqing.

Tile-Based Two-Dimensional Phase Unwrapping for Digital Holography Using a Modular Framework.

A variety of physical and biomedical imaging techniques, such as digital holography, interferometric synthetic aperture radar (InSAR), or magnetic resonance imaging (MRI) enable measurement of the phase of a physical quantity additionally to its amplitude. However, the phase can commonly only be measured modulo 2π, as a so called wrapped phase map. Phase unwrapping is the process of obtaining the underlying physical phase map from the wrapped phase. Tile-based phase unwrapping algorithms operate by first tessellating the phase map, then unwrapping individual tiles, and finally merging them to a continuous phase map. They can be implemented computationally efficiently and are robust to noise. However, they are prone to failure in the presence of phase residues or erroneous unwraps of single tiles. We tried to overcome these shortcomings by creating novel tile unwrapping and merging algorithms as well as creating a framework that allows to combine them in modular fashion. To increase the robustness of the tile unwrapping step, we implemented a model-based algorithm that makes efficient use of linear algebra to unwrap individual tiles. Furthermore, we adapted an established pixel-based unwrapping algorithm to create a quality guided tile merger. These original algorithms as well as previously existing ones were implemented in a modular phase unwrapping C++ framework. By examining different combinations of unwrapping and merging algorithms we compared our method to existing approaches. We could show that the appropriate choice of unwrapping and merging algorithms can significantly improve the unwrapped result in the presence of phase residues and noise. Beyond that, our modular framework allows for efficient design and test of new tile-based phase unwrapping algorithms. The software developed in this study is freely available.

Aptamer for imaging and therapeutic targeting of brain tumor glioblastoma.

Aptamers are short single-stranded nucleic acids (RNA or ssDNA), identified by an in vitro selection process, denominated SELEX, from a partially random oligonucleotide library. They bind to a molecular target, a protein or other complex macromolecular structures of interest with high affinity and specificity, comparable to those of antibodies. Recently, aptamer selection protocols were developed for targeting living cells, including tumors. Chemical modifications of the aptamers and modalities of their detection and delivery systems are already available with high selectivity and targeting ability for the desired cancer cell type, making them promising for diagnosis and therapy. Glioblastoma multiformae represents the most malignant and fatal stage of glioma, and is also the most frequent brain tumor. Glioblastoma-specific aptamers were developed by either targeting the whole cell surface or known glioma biomarkers. These aptamers may gain importance for imaging, tumor cell isolation from biopsies and drug delivery. In biomedical imaging techniques, aptamers coupled with radionuclide or fluorescent labels, bioconjugates and nanoparticles offer an advanced, noninvasive manner for defining the glioblastoma tissue border. Though single modality aptamer imaging probes have some limitations, these are overcome by the use of multimodal probes. Due to selectivity and chemical characteristics, aptamers can be coupled to functionalized nanoparticles and loaded with a drug, appeared promising for in vivo targeting of glioblastoma. Finally, aptamers are effective mediators for gene silencing when coupled to small interfering RNA and a viral vector, thus providing a novel tool with enhanced targeting capability in drug delivery, designed for tailored treatment of glioblastoma patients.

Biomedical Imaging in Implantable Drug Delivery Systems.

Implantable drug delivery systems (DDS) provide a platform for sustained release of therapeutic agents over a period of weeks to months and sometimes years. Such strategies are typically used clinically to increase patient compliance by replacing frequent administration of drugs such as contraceptives and hormones to maintain plasma concentration within the therapeutic window. Implantable or injectable systems have also been investigated as a means of local drug administration which favors high drug concentration at a site of interest, such as a tumor, while reducing systemic drug exposure to minimize unwanted side effects. Significant advances in the field of local DDS have led to increasingly sophisticated technology with new challenges including quantification of local and systemic pharmacokinetics and implant- body interactions. Because many of these sought-after parameters are highly dependent on the tissue properties at the implantation site, and rarely represented adequately with in vitro models, new nondestructive techniques that can be used to study implants in situ are highly desirable. Versatile imaging tools can meet this need and provide quantitative data on morphological and functional aspects of implantable systems. The focus of this review article is an overview of current biomedical imaging techniques, including magnetic resonance imaging (MRI), ultrasound imaging, optical imaging, X-ray and computed tomography (CT), and their application in evaluation of implantable DDS.

Near-Infrared Spectroscopy Technology in Typically Fluent Speakers and Persons who Stutter

Near-infrared spectroscopy (NIRS) is a biomedical optical imaging technique that is used to measure real-time functional brain activity. NIRS uses non-invasive infrared light to measure oxy-, de-oxy, and total hemoglobin concentration at the surface of the cerebral cortex. Hemoglobin concentration is monitored through the use of light scattering and tissue absorption. NIRS is advantageous over other techniques (e.g., EEG, MRI, PET etc.) because it does not utilize harmful radiation or an extrinsic contrast agent. It is also portable and is a low cost technology to administer. NIRS can also be used with infants, young children, and adults. Since its discovery, NIRS has been used to study Alzheimer's disease, verbal fluency, language processing, epilepsy, frontal lateralization in speech tasks, cerebral hemodynamics, visual stimulation, odor stimulation, chronic schizophrenia, and other conditions. We have used NIRS to measure hemoglobin changes in typically fluent speakers (TFS) and persons who stutter (PWS). Our NIRS device has 16 sources and 24 detectors to measure haemoglobin concentration changes during speech and non-speech tasks for TFS and PWS. Our participants ranged in age from 10 to young adulthood. Measurements were taken during three conditions: Speakers were asked to read out loud, to engage in spontaneous speech, and to sit for a rest period. The purpose of this study was to determine whether there were haemoglobin concentration changes in TFS and PWS while they engaged in speech and non-speech tasks. Initial results indicate that speech tasks caused hemoglobin concentration changes. A more in-depth analysis of our technology and pilot data will be presented.

Multi-parameter photoacoustic imaging and its application in biomedicine

Photoacoustic imaging is a hybrid imaging technique based on the photoacoustic effect. As a non-invasive and non-ionizing modality, photoacoustic imaging takes the both merits of the conventional acoustic imaging and optical imaging. Firstly, the contrast of photoacoustic imaging primarily depends on the optical absorption. The unique optical spectra of atoms and molecules makes optical methods to be a widely used modality to probe the molecular and chemical information of biological tissue. Therefore, photoacoustic imaging has its inherent advantage in high-contrast functional and physiological imaging of biological tissue, as well as the optical imaging method. Secondly, photoacoustic imaging has the high spatial resolution in deep tissue in comparison with the pure optical imaging method. Since the strongly optical scattering in biological tissue, pure optical imaging method is difficult to obtain the high-resolution image in the tissue deeper than ～1 mm. Whereas, acoustic wave suffers much less from scattering than optical wave, the acoustic scattering coefficient is about 2-3 orders of magnitude less than the optical scattering coefficient. Photoacoustic imaging can achieve a fine resolution in deep tissue, which equivalent to 1/200 of the imaging depth. Thirdly, non-ionizing radiation used for photoacoustic imaging is much safer than X-ray. Moreover, the low-temperature rises make photoacoustic imaging be safely used in live tissue. A laser-induced temperature rise of 1 mK yields an initial pressure of ～800 Pa in soft tissue. Such a sound pressure level has reached the sensitivities of typical ultrasonic transducers. Fourthly, photoacoustic imaging has the ability of extracting multiple contrasts, including biochemical parameter, biomechanical parameter, blood velocity distribution, tissue temperature, and microstructure information. Photoacoustic imaging can capture more specific and reliable information about the tissue structure, function, metabolism, molecule, and gene. As a result, photoacoustic imaging has become one of the fastest growing biomedical imaging techniques in the past decade.#br#In this review, we will explain photoacoustic effect and the principle of photoacoustic imaging. Then, we introduce the two classical photoacoustic imaging schemes, including photoacoustic tomography and photoacoustic microscopy. Their main specifications, such as resolution, are also preflents. We review the ability of photoacoustic imaging in extracting multiple contrasts and discuss their biomedicine applications. In addition, we also introduce the remarkable breakthroughs in super-resolution photoacoustic imaging. Finally, we look the further development and the limitations of photoacoustic imaging.

Contrast agents for photoacoustic and thermoacoustic imaging: a review.

Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed.

Magnetic particle imaging with tailored iron oxide nanoparticle tracers.

Magnetic particle imaging (MPI) shows promise for medical imaging, particularly in angiography of patients with chronic kidney disease. As the first biomedical imaging technique that truly depends on nanoscale materials properties, MPI requires highly optimized magnetic nanoparticle tracers to generate quality images. Until now, researchers have relied on tracers optimized for MRI T2(∗) -weighted imaging that are sub-optimal for MPI. Here, we describe new tracers tailored to MPI's unique physics, synthesized using an organic-phase process and functionalized to ensure biocompatibility and adequate in vivo circulation time. Tailored tracers showed up to 3 × greater signal-to-noise ratio and better spatial resolution than existing commercial tracers in MPI images of phantoms.

Slew-rate dependence of tracer magnetization response in magnetic particle imaging.

Magnetic Particle Imaging (MPI) is a new biomedical imaging technique that produces real-time, high-resolution tomographic images of superparamagnetic iron oxide nanoparticle tracers. Currently, 25 kHz and 20 mT/μ0 excitation fields are common in MPI, but lower field amplitudes may be necessary for patient safety in future designs. Here, we address fundamental questions about MPI tracer magnetization dynamics and predict tracer performance in future scanners that employ new combinations of excitation field amplitude (Ho ) and frequency (ω). Using an optimized, monodisperse MPI tracer, we studied how several combinations of drive field frequencies and amplitudes affect the tracer's response, using Magnetic Particle Spectrometry and AC hysteresis, for drive field conditions at 15.5, 26, and 40.2 kHz, with field amplitudes ranging from 7 to 52 mT/μ0. For both fluid and immobilized nanoparticle samples, we determined that magnetic response was dominated by Néel reversal. Furthermore, we observed that the peak slew-rate (ωHo) determined the tracer magnetic response. Smaller amplitudes provided correspondingly smaller field of view, sometimes resulting in excitation of minor hysteresis loops. Changing the drive field conditions but keeping the peak slew-rate constant kept the tracer response almost the same. Higher peak slew-rates led to reduced maximum signal intensity and greater coercivity in the tracer response. Our experimental results were in reasonable agreement with Stoner-Wohlfarth model based theories.

Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer.

Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer.

High-contrast coherent terahertz imaging of porcine tissue via swept-frequency feedback interferometry.

There is considerable interest in the interrogation of biological tissue at terahertz (THz) frequencies, largely due to the contrast in the optical properties of different biological tissues which occur in this electro-magnetic radiation band. Of particular interest are THz biomedical images, which have the potential to highlight different information than those acquired in other frequency bands, thereby providing an augmented picture of biological structures. In this work, we demonstrate the feasibility of an interferometric biological imaging technique using a THz quantum cascade laser (QCL) operating at 2.59 THz to perform coherent imaging of porcine tissue samples. We show the potential of this new THz biomedical imaging technique for in vivo studies, by virtue of its reflection geometry and useful tissue penetration depth enabled by the large THz powers emitted by the quantum cascade laser used in this work. The observed clustering of interferometric tissue signatures opens a pathway towards automatic techniques for the discrimination of healthy tissue types for the study of normal physiology and possible therapeutic approaches.

MRI Meets MPI: a bimodal MPI-MRI tomograph.

While magnetic particle imaging (MPI) constitutes a novel biomedical imaging technique for tracking superparamagnetic nanoparticles in vivo, unlike magnetic resonance imaging (MRI), it cannot provide anatomical background information. Until now these two modalities have been performed in separate scanners and image co-registration has been hampered by the need to reposition the sample in both systems as similarly as possible. This paper presents a bimodal MPI-MRI-tomograph that combines both modalities in a single system.MPI and MRI images can thus be acquired without moving the sample or replacing any parts in the setup. The images acquired with the presented setup show excellent agreement between the localization of the nanoparticles in MPI and the MRI background data. A combination of two highly complementary imaging modalities has been achieved.