For contrast ultrasound imaging, the most efficient contrast agents comprise highly compressible gas-filled microbubbles. These micrometer-sized particles are typically filled with low-solubility ...perfluorocarbon gases, and coated with a thin shell, often a lipid monolayer. These particles circulate in the bloodstream for several minutes; they demonstrate good safety and are already in widespread clinical use as blood pool agents with very low dosage necessary (sub-mg per injection). As ultrasound is an ubiquitous medical imaging modality, with tens of millions of exams conducted annually, its use for molecular/targeted imaging of biomarkers of disease may enable wider implementation of personalised medicine applications, precision medicine, non-invasive quantification of biomarkers, targeted guidance of biopsy and therapy in real time. To achieve this capability, microbubbles are decorated with targeting ligands, possessing specific affinity towards vascular biomarkers of disease, such as tumour neovasculature or areas of inflammation, ischaemia-reperfusion injury or ischaemic memory. Once bound to the target, microbubbles can be selectively visualised to delineate disease location by ultrasound imaging. This review discusses the general design trends and approaches for such molecular ultrasound imaging agents, which are currently at the advanced stages of development, and are evolving towards widespread clinical trials.
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Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
ABSTRACTUltrasound is the most widely used medical imaging modality worldwide. It is abundant, extremely safe, portable, and inexpensive. In this review, we consider some of the current development ...trends for ultrasound imaging, which build upon its current strength and the popularity it experiences among medical imaging professional users.Ultrasound has rapidly expanded beyond traditional radiology departments and cardiology practices. Computing power and data processing capabilities of commonly available electronics put ultrasound systems in a lab coat pocket or on a userʼs mobile phone. Taking advantage of new contributions and discoveries in ultrasound physics, signal processing algorithms, and electronics, the performance of ultrasound systems and transducers have progressed in terms of them becoming smaller, with higher imaging performance, and having lower cost. Ultrasound operates in real time, now at ultrafast speeds; kilohertz frame rates are already achieved by many systems.Ultrasound has progressed beyond anatomical imaging and monitoring blood flow in large vessels. With clinical approval of ultrasound contrast agents (gas-filled microbubbles) that are administered in the bloodstream, tissue perfusion studies are now routine. Through the use of modern ultrasound pulse sequences, individual microbubbles, with subpicogram mass, can be detected and observed in real time, many centimeters deep in the body. Ultrasound imaging has broken the wavelength barrier; by tracking positions of microbubbles within the vasculature, superresolution imaging has been made possible. Ultrasound can now trace the smallest vessels and capillaries, and obtain blood velocity data in those vessels.Molecular ultrasound imaging has now moved closer to clinic; the use of microbubbles with a specific affinity to endothelial biomarkers allows selective accumulation and retention of ultrasound contrast in the areas of ischemic injury, inflammation, or neoangiogenesis. This will aid in noninvasive molecular imaging and may provide additional help with real-time guidance of biopsy, surgery, and ablation procedures.The ultrasound field can be tightly focused inside the body, many centimeters deep, with millimeter precision, and ablate lesions by energy deposition, with thermal or mechanical bioeffects. Some of such treatments are already in clinical use, with more indications progressing through the clinical trial stage. In conjunction with intravascular microbubbles, focused ultrasound can be used for tissue-specific drug delivery; localized triggered release of sequestered drugs from particles in the bloodstream may take time to get to clinic. A combination of intravascular microbubbles with circulating drug and low-power ultrasound allows transient opening of vascular endothelial barriers, including blood-brain barrier; this approach has reached clinical trial stage. Therefore, the drugs that normally would not be getting to the target tissue in the brain will now have an opportunity to produce therapeutic efficacy.Overall, medical ultrasound is developing at a brisk rate, even in an environment where other imaging modalities are also advancing rapidly and may be considered more lucrative. With all the current advances that we discuss, and many more to come, ultrasound may help solve many problems that modern medicine is facing.
ABSTRACTDuring the past decade, ultrasound has expanded medical imaging well beyond the “traditional” radiology settinga combination of portability, low cost, and ease of use makes ultrasound imaging ...an indispensable tool for radiologists as well as for other medical professionals who need to obtain imaging diagnosis or guide a therapeutic intervention quickly and efficiently. Ultrasound combines excellent ability for deep penetration into soft tissues with very good spatial resolution, with only a few exceptions (ie, those involving overlying bone or gas). Real-time imaging (up to hundreds and thousands of frames per second) enables guidance of therapeutic procedures and biopsies; characterization of the mechanical properties of the tissues greatly aids with the accuracy of the procedures. The ability of ultrasound to deposit energy locally brings about the potential for localized intervention encompassing the followingtissue ablation, enhancing penetration through the natural barriers to drug delivery in the body and triggering drug release from carrier microparticles and nanoparticles. The use of microbubble contrast agents brings the ability to monitor and quantify tissue perfusion, and microbubble targeting with ligand-decorated microbubbles brings the ability to obtain molecular biomarker information, that is, ultrasound molecular imaging. Overall, ultrasound has become the most widely used imaging modality in modern medicine; it will continue to grow and expand.
We showed previously that prior exposure to a modified ultrasound regimen prevents kidney ischemia-reperfusion injury (IRI) likely via the splenic cholinergic anti-inflammatory pathway (CAP) and α7 ...nicotinic acetylcholine receptors (α7nAChR). However, it is unclear how ultrasound stimulates the splenic CAP. Further investigating the role of the spleen in ischemic injury, we found that prior splenectomy (-7d) or chemical sympathectomy of the spleen with 6-hydroxydopamine (6OHDA; -14d) exacerbated injury after subthreshold (24-minute ischemia) IRI. 6-OHDA-induced splenic denervation also prevented ultrasound-induced protection of kidneys from moderate (26-minute ischemia) IRI. Ultrasound-induced protection required hematopoietic but not parenchymal α7nAChRs, as shown by experiments in bone marrow chimeras generated with wild-type and α7nAChR(-/-) mice. Ultrasound protection was associated with reduced expression of circulating and kidney-derived cytokines. However, splenocytes isolated from mice 24 hours after ultrasound treatment released more IL-6 ex vivo in response to LPS than splenocytes from sham mice. Adoptive transfer of splenocytes from ultrasound-treated (but not sham) mice to naïve mice was sufficient to protect kidneys of recipient mice from IRI. Ultrasound treatment 24 hours before cecal ligation puncture-induced sepsis was effective in reducing plasma creatinine in this model of AKI. Thus, splenocytes of ultrasound-treated mice are capable of modulating IRI in vivo, supporting our ongoing hypothesis that a modified ultrasound regimen has therapeutic potential for AKI and other inflammatory conditions.
Photoacoustic microscopy (PAM) capitalizes on the optical absorption of blood hemoglobin to enable label-free high-contrast imaging of the cerebral microvasculature in vivo. Although time-resolved ...ultrasonic detection equips PAM with depth-sectioning capability, most of the data at depths are often obscured by acoustic reverberant artifacts from superficial cortical layers and thus unusable. In this paper, we present a first-of-a-kind dictionary learning algorithm to remove the reverberant signal while preserving underlying microvascular anatomy. This algorithm was validated in vitro, using dyed beads embedded in an optically transparent polydimethylsiloxane phantom. Subsequently, we demonstrated in the live mouse brain that the algorithm can suppress reverberant artifacts by 21.0 ± 5.4 dB, enabling depth-resolved PAM up to 500 µm from the brain surface.
High-resolution quantitative imaging of cerebral oxygen metabolism in mice is crucial for understanding brain functions and formulating new strategies to treat neurological disorders, but remains a ...challenge. Here, we report on our newly developed ultrasound-aided multi-parametric photoacoustic microscopy (PAM), which enables simultaneous quantification of the total concentration of hemoglobin (CHb), the oxygen saturation of hemoglobin (sO2), and cerebral blood flow (CBF) at the microscopic level and through the intact mouse skull. The three-dimensional skull and vascular anatomies delineated by the dual-contrast (i.e., ultrasonic and photoacoustic) system provide important guidance for dynamically focused contour scan and vessel orientation-dependent correction of CBF, respectively. Moreover, bi-directional raster scan allows determining the direction of blood flow in individual vessels. Capable of imaging all three hemodynamic parameters at the same spatiotemporal scale, our ultrasound-aided PAM fills a critical gap in preclinical neuroimaging and lays the foundation for high-resolution mapping of the cerebral metabolic rate of oxygen (CMRO2)-a quantitative index of cerebral oxygen metabolism. This technical innovation is expected to shed new light on the mechanism and treatment of a broad spectrum of neurological disorders, including Alzheimer's disease and ischemic stroke.
Photoacoustic microscopy (PAM) leverages the optical absorption contrast of blood hemoglobin for high-resolution, multi-parametric imaging of the microvasculature in vivo . However, to quantify the ...blood flow speed, dense spatial sampling is required to assess blood flow-induced loss of correlation of sequentially acquired A-line signals, resulting in increased laser pulse repetition rate and consequently optical fluence. To address this issue, we have developed a sparse modeling approach for blood flow quantification based on downsampled PAM data. Evaluation of its performance both in vitro and in vivo shows that this sparse modeling method can accurately recover the substantially downsampled data (up to 8 times) for correlation-based blood flow analysis, with a relative error of 12.7 ± 6.1 % across 10 datasets in vitro and 12.7 ± 12.1 % in vivo for data downsampled 8 times. Reconstruction with the proposed method is on par with recovery using compressive sensing, which exhibits an error of 12.0 ± 7.9 % in vitro and 33.86 ± 26.18 % in vivo for data downsampled 8 times. Both methods outperform bicubic interpolation, which shows an error of 15.95 ± 9.85 % in vitro and 110.7 ± 87.1 % in vivo for data downsampled 8 times.
Fabrication of Two Flow Phantoms for Doppler Ultrasound Imaging Zhou, Xiaowei; Kenwright, David A.; Wang, Shiying ...
IEEE transactions on ultrasonics, ferroelectrics and frequency control/IEEE transactions on ultrasonics, ferroelectrics, and frequency control,
2017-Jan., 2017-01-00, 2017-1-00, 20170101, Letnik:
64, Številka:
1
Journal Article
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Flow phantoms are widely used in studies associated with Doppler ultrasound measurements, acting as an effective experimental validation system in cardiovascular-related research and in new ...algorithm/instrumentation development. The development of materials that match the acoustic and mechanical properties of the vascular system is of great interest while designing flow phantoms. Although recipes that meet the flow phantom standard defined by the International Electrotechnical Commission 61685 are already available in the literature, the standard procedure for material preparations and phantom fabrications has not been well established. In this paper, two types of flow phantoms, with and without blood vessel mimic, are described in detail in terms of the material preparation and phantom fabrication. The phantom materials chosen for the two phantoms are from published phantom studies, and their physical properties have been investigated previously. Both the flow phantoms have been scanned by ultrasound scanners and images from different modes are presented. These phantoms may be used in the validation and characterization of Doppler ultrasound measurements in blood vessels with a diameter above 1 mm.
Microbubbles (MB) are widely used as contrast agents to perform contrast-enhanced ultrasound (CEUS) imaging and as acoustic amplifiers of mechanical bioeffects incited by therapeutic-level ...ultrasound. The distribution of MBs in the brain is not yet fully understood, thereby limiting intra-operative CEUS guidance or MB-based FUS treatments. In this paper we describe a robust platform for quantification of MB distribution in the human brain, allowing to quantitatively discriminate between tumoral and normal brain tissues and we provide new information regarding real-time cerebral MBs distribution. Intraoperative CEUS imaging was performed during surgical tumor resection using an ultrasound machine (MyLab Twice, Esaote, Italy) equipped with a multifrequency (3-11 MHz) linear array probe (LA332) and a specific low mechanical index (MI < 0.4) CEUS algorithm (CnTi, Esaote, Italy; section thickness, 0.245 cm) for non-destructive continuous MBs imaging. CEUS acquisition is started by enabling the CnTI PEN-M algorithm automatically setting the MI at 0.4 with a center frequency of 2.94 MHz-10 Hz frame rate at 80 mm-allowing for continuous non-destructive MBs imaging. 19 ultrasound image sets of adequate length were selected and retrospectively analyzed using a custom image processing software for quantitative analysis of echo power. Regions of interest (ROIs) were drawn on key structures (artery-tumor-white matter) by a blinded neurosurgeon, following which peak enhancement and time intensity curves (TICs) were quantified. CEUS images revealed clear qualitative differences in MB distribution: arteries showed the earliest and highest enhancement among all structures, followed by tumor and white matter regions, respectively. The custom software built for quantitative analysis effectively captured these differences. Quantified peak intensities showed regions containing artery, tumor or white matter structures having an average MB intensity of 0.584, 0.436 and 0.175 units, respectively. Moreover, the normalized area under TICs revealed the time of flight for MB to be significantly lower in brain tissue as compared with tumor tissue. Significant heterogeneities in TICs were also observed within different regions of the same brain lesion. In this study, we provide the most comprehensive strategy for accurate quantitative analysis of MBs distribution in the human brain by means of CEUS intraoperative imaging. Furthermore our results demonstrate that CEUS imaging quantitative analysis enables discernment between different types of brain tumors as well as regions and structures within the brain. Similar considerations will be important for the planning and implementation of MB-based imaging or treatments in the future.
Recent research has shown that targeted ultrasound contrast microbubbles achieve specific adhesion to regions of intravascular pathology, but not in areas of high flow. It has been suggested that ...acoustic radiation can be used to force free-stream microbubbles toward the target, but this has not been verified for actual targeted contrast agents. We present evidence that acoustic radiation indeed increases the specific targeted accumulation of microbubbles. Lipid microbubbles bearing an antibody as a targeting ligand were infused through a microcapillary flow chamber coated with P-selectin as the target protein. A 2.0 MHz ultrasonic pulse was applied perpendicular to the flow direction. Microbubble accumulation was observed on the flow chamber surface opposite the transducer. An acoustic pressure of 122 kPa enhanced microbubble adhesion up to 60-fold in a microbubble concentration range of 0.25 /spl times/ 10/sup 6/ to 75 /spl times/ 10/sup 6/ ml/sup -1/. Acoustic pressure mediated the greatest adhesion enhancement at concentrations within the clinical dosing range. Acoustic pressure enhanced targeting nearly 80-fold at a wall shear rate of 1244 s/sup -1/, suggesting that this mechanism is appropriate for achieving targeted microbubble delivery in high-flow vessels. Microbubble adhesion increased with the square of acoustic pressure between 25 and 122 kPa, and decreased substantially at higher pressures.
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