Mechanically Rotating Intravascular Ultrasound (IVUS) Transducer: A Review.

Intravascular ultrasound (IVUS) is a valuable imaging modality for the diagnosis of atherosclerosis. It provides useful clinical information, such as lumen size, vessel wall thickness, and plaque composition, by providing a cross-sectional vascular image. For several decades, IVUS has made remarkable progress in improving the accuracy of diagnosing cardiovascular disease that remains the leading cause of death globally. As the quality of IVUS images mainly depends on the performance of the IVUS transducer, various IVUS transducers have been developed. Therefore, in this review, recently developed mechanically rotating IVUS transducers, especially ones exploiting piezoelectric ceramics or single crystals, are discussed. In addition, this review addresses the history and technical challenges in the development of IVUS transducers and the prospects of next-generation IVUS transducers.

Transrectal Ultrasound and Photoacoustic Imaging Probe for Diagnosis of Prostate Cancer.

A combined transrectal ultrasound and photoacoustic (TRUS-PA) imaging probe was developed for the clear visualization of morphological changes and microvasculature distribution in the prostate, as this is required for accurate diagnosis and biopsy. The probe consisted of a miniaturized 128-element 7 MHz convex array transducer with 134.5° field-of-view (FOV), a bifurcated optical fiber bundle, and two optical lenses. The design goal was to make the size of the TRUS-PA probe similar to that of general TRUS probes (i.e., about 20 mm), for the convenience of the patients. New flexible printed circuit board (FPCB), acoustic structure, and optical lens were developed to meet the requirement of the probe size, as well as to realize a high-performance TRUS-PA probe. In visual assessment, the PA signals obtained with the optical lens were 2.98 times higher than those without the lens. Moreover, the in vivo experiment with the xenograft BALB/c (Albino, Immunodeficient Inbred Strain) mouse model showed that TRUS-PA probe was able to acquire the entire PA image of the mouse tight behind the porcine intestine about 25 mm depth. From the ex vivo and in vivo experimental results, it can be concluded that the developed TRUS-PA probe is capable of improving PA image quality, even though the TRUS-PA probe has a cross-section size and an FOV comparable to those of general TRUS probes.

A 40-MHz Ultrasound Transducer with an Angled Aperture for Guiding Percutaneous Revascularization of Chronic Total Occlusion: A Feasibility Study.

Complete blockage of a coronary artery, called chronic total occlusion (CTO), frequently occurs due to atherosclerosis. To reopen the obstructed blood vessels with a stent, guidewire crossing is performed with the help of angiography that can provide the location of CTO lesions and the image of guidewire tip. Since angiography is incapable of imaging inside a CTO lesion, the surgeons are blind during guidewire crossing. For this reason, the success rate of guidewire crossing relies upon the proficiency of the surgeon, which is considerably reduced from 69.0% to 32.5% if extensive calcification, not penetrated by a guidewire, exists in CTO lesions. In this paper, a recently developed 40-MHz forward-looking intravascular ultrasound (FL⁻IVUS) transducer to visualize calcification within CTO lesions is reported. This transducer consists of a single element angled aperture and a guidewire passage. The aperture is spherically deformed to have a focal length of 3 mm in order to improve spatial resolution of FL⁻IVUS images. The angle between the beam direction and the axis of rotation is designed to be 30° to effectively visualize calcification within a CTO lesion as well as the blood vessel wall. The experimental results demonstrated that the developed FL⁻IVUS transducer facilitates visualization of calcification within CTO lesions and makes it possible to help the surgeon make decisions about whether to push the guidewire in order to cross the lesion or to change the surgical procedure.

A 35 MHz/105 MHz Dual-Element Focused Transducer for Intravascular Ultrasound Tissue Imaging Using the Third Harmonic.

The superharmonic imaging of tissue has the potential for high spatial and contrast resolutions, compared to the fundamental and second harmonic imaging. For this technique, the spectral bandwidth of an ultrasound transducer is divided for transmission of ultrasound and reception of its superharmonics (i.e., higher than the second harmonic). Due to the spectral division for the transmission and reception, transmitted ultrasound energy is not sufficient to induce superharmonics in media without using contrast agents, and it is difficult that a transducer has a -6 dB fractional bandwidth of higher than 100%. For the superharmonic imaging of tissue, thus, multi-frequency array transducers are the best choice if available; transmit and receive elements are separate and have different center frequencies. However, the construction of a multi-frequency transducer for intravascular ultrasound (IVUS) imaging is particularly demanding because of its small size of less than 1 mm. Here, we report a recently developed dual-element focused IVUS transducer for the third harmonic imaging of tissue, which consists of a 35-MHz element for ultrasound transmission and a 105-MHz element for third harmonic reception. For high quality third harmonic imaging, both elements were fabricated to have the same focus at 2.5 mm. The results of tissue mimicking phantom tests demonstrated that the third harmonic images produced by the developed transducer had higher spatial resolution and deeper imaging depth than the fundamental images.

Clue to Understanding the Janus Behavior of Eumelanin: Investigating the Relationship between Hierarchical Assembly Structure of Eumelanin and Its Photophysical Properties.

The contradictory biological function of eumelanin (photoprotection vs photosensitization) has long been a topic of debate in a wide range of disciplines such as chemistry, physics and biology. For understanding full spectrum of eumelanin's photobiological aspect, revealing how eumelanin's complex structural organization dictates its photophysical properties is critical step. Here, we report a practical approach to controlling the hierarchically assembled structure of natural eumelanin, which leads to disassembly of its structure into subunits and oxidized subunits, respectively. Based on the well-characterized model system, it was possible to systematically determine how the photophysical properties of eumelanin are ruled by its hierarchical assembly organization. Particularly, our experiments reveal that the chemical oxidation of eumelanin's subunits, which leads to delamination of their stacked layer structure, is critical to significantly increase their photochemical reactivity to generate ROS under UV irradiation. This result provides clear experimental evidence that oxidative degradation of eumelanin, which might be induced by phagosomal enzymatic activity in the process of melanomagenesis, is responsible for triggering the negative photobiological role of eumelanin such as ROS source needed for development of malignant melanoma.

Design and Fabrication of Double-Focused Ultrasound Transducers to Achieve Tight Focusing.

Beauty treatment for skin requires a high-intensity focused ultrasound (HIFU) transducer to generate coagulative necrosis in a small focal volume (e.g., 1 mm³) placed at a shallow depth (3-4.5 mm from the skin surface). For this, it is desirable to make the F-number as small as possible under the largest possible aperture in order to generate ultrasound energy high enough to induce tissue coagulation in such a small focal volume. However, satisfying both conditions at the same time is demanding. To meet the requirements, this paper, therefore, proposes a double-focusing technique, in which the aperture of an ultrasound transducer is spherically shaped for initial focusing and an acoustic lens is used to finally focus ultrasound on a target depth of treatment; it is possible to achieve the F-number of unity or less while keeping the aperture of a transducer as large as possible. In accordance with the proposed method, we designed and fabricated a 7-MHz double-focused ultrasound transducer. The experimental results demonstrated that the fabricated double-focused transducer had a focal length of 10.2 mm reduced from an initial focal length of 15.2 mm and, thus, the F-number changed from 1.52 to 1.02. Based on the results, we concluded that the proposed double-focusing method is suitable to decrease F-number while maintaining a large aperture size.

Does adding diffuse optical tomography to sonography improve differentiation between benign and malignant breast lesions? Observer performance study.

OBJECTIVES: The purpose of this study was to investigate the added value of diffuse optical tomographic categories combined with conventional sonography for differentiating between benign and malignant breast lesions. METHODS: In this retrospective database review, we included 145 breast lesions (116 benign and 29 malignant) from 145 women (mean age, 46 years; range, 16-86 years). Five radiologists independently reviewed sonograms with and without a diffuse optical tomographic category. Each lesion was scored on a scale of 0% to 100% for suspicion of malignancy and rated according to the American College of Radiology Breast Imaging Reporting and Data System classification. Diagnostic performance was analyzed by comparing area under receiver operating characteristic curve values. Reader agreement was assessed by intraclass correlation coefficients. RESULTS: In the multireader multicase receiver operating characteristic analysis, adding a diffuse optical tomographic category to sonography improved the diagnostic accuracy of sonography (mean areas under the curve, 0.923 for sonography alone and 0.969 for sonography with diffuse optical tomography; P = .039). The interobserver correlation was also improved (0.798 for sonography alone and 0.904 for sonography with diffuse optical tomography). The specificity increased for 4 reviewers from a mean of 19.5% to 45.8% (P < .001 for reviewers 1-4; P = .238 for reviewer 5) with no significant change in the sensitivity. When the diffuse optical tomographic category was applied strictly, the specificity increased for all reviewers from a mean of 19.5% to 68.3% (P < .001 for all reviewers) with no significant change in the sensitivity. CONCLUSIONS: The addition of diffuse optical tomographic categories to sonography may improve diagnostic performance and markedly decrease false-positive biopsy recommendations.

Thermal therapeutic method for selective treatment of deep-lying tissue by combining laser and high-intensity focused ultrasound energy.

Photothermal therapy is performed by delivering laser radiation into the target lesion containing tissue chromophores so as to induce localized heating. For high treatment efficacy, the laser wavelength should be selected to maximize the absorption of incident laser radiation in the tissue chromophores. However, even with the optimal laser wavelength, both the absorption and the scattering of laser energy in tissue openly hamper treatment efficacy in deep-lying lesions. To overcome the limitation, we propose a dual thermal therapeutic method in which both laser and acoustic energies are transmitted to increase therapeutic depth while maintaining high target selectivity of photothermal therapy. Through skin-mimicking phantom experiments, it was verified that the two different energies are complementary in elevation of tissue temperature, and the treatment depth using laser radiation is increased along with acoustic energy.

Intelligent Bladder Volume Monitoring for Wearable Ultrasound Devices: Enhancing Accuracy Through Deep Learning-Based Coarse-to-Fine Shape Estimation.

Accurate and continuous bladder volume monitoring is crucial for managing urinary dysfunctions. Wearable ultrasound (US) devices offer a solution by enabling noninvasive and real-time monitoring. Previous studies have limitations in power consumption and computation cost or quantitative volume estimation capability. To alleviate this, we present a novel pipeline that effectively integrates conventional feature extraction and deep learning (DL) to achieve continuous quantitative bladder volume monitoring efficiently. Particularly, in the proposed pipeline, bladder shape is coarsely estimated by a simple bladder wall detection algorithm in wearable devices, and the bladder wall coordinates are wirelessly transferred to an external server. Subsequently, a roughly estimated bladder shape from the wall coordinates is refined in an external server with a diffusion-based model. With this approach, power consumption and computation costs on wearable devices remained low, while fully harnessing the potential of DL for accurate shape estimation. To evaluate the proposed pipeline, we collected a dataset of bladder US images and RF signals from 250 patients. By simulating data acquisition from wearable devices using the dataset, we replicated real-world scenarios and validated the proposed method within these scenarios. Experimental results exhibit superior improvements, including +9.32% of IoU value in 2-D segmentation and -22.06 of RMSE in bladder volume regression compared to state-of-the-art (SOTA) performance from alternative methods, emphasizing the potential of this approach in continuous bladder volume monitoring in clinical settings. Therefore, this study effectively bridges the gap between accurate bladder volume estimation and the practical deployment of wearable US devices, promising improved patient care and quality of life.

Improving the quality of ultrasound images acquired using a therapeutic transducer.

To enhance the effectiveness and safety of focused ultrasound (FUS) therapy, ultrasound image-based guidance and treatment monitoring are crucial. However, the use of FUS transducers for both therapy and imaging is impractical due to their low spatial resolution, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). To address this issue, we propose a new method that significantly improve the quality of images obtained by a FUS transducer. The proposed method employs coded excitation to enhance SNR and Wiener deconvolution to solve the problem of low axial resolution resulting from the narrow spectral bandwidth of FUS transducers. Specifically, the method eliminates the impulse response of a FUS transducer from received ultrasound signals using Wiener deconvolution, and pulse compression is performed using a mismatched filter. Simulation and commercial phantom experiments confirmed that the proposed method significantly improves the quality of images acquired by the FUS transducer. The -6 dB axial resolution was improved 1.27 mm to 0.37 mm that was similar to the resolution achieved by the imaging transducer, i.e., 0.33 mm. SNR and CNR also increased from 16.5 dB and 0.69 to 29.1 dB and 3.03, respectively, that were also similar to those by the imaging transducer (27.8 dB and 3.16). Based on the results, we believe that the proposed method has great potential to enhance the clinical utility of FUS transducers in ultrasound image-guided therapy.

Enhancement of photoacoustic image quality by sound speed correction: ex vivo evaluation.

Real-time photoacoustic (PA) imaging involves beamforming methods using an assumed fixed sound speed, typically 1540 m/s in soft tissue. This leads to degradation of PA image quality because the true sound speed changes as PA signal propagates through different types of soft tissues: the range from 1450 m/s to 1600 m/s. This paper proposes a new method for estimating an optimal sound speed to enhance the cross-sectional PA image quality. The optimal sound speed is determined when coherent factor with the sound speed is maximized. The proposed method was validated through simulation and ex vivo experiments with microcalcification-contained breast cancer specimen. The experimental results demonstrated that the best lateral resolution of PA images of microcalcifications can be achieved when the optimal sound speed is utilized.

Elevational Synthetic Aperture Focusing for Three-Dimensional Photoacoustic Imaging Using a Clinical One-Dimensional Array Transducer.

OBJECTIVE: Two-dimensional (2D) photoacoustic (PA) imaging based on array transducers provide high spatial resolution in the lateral direction by adopting receive dynamic focusing. However, the quality of PA image is often deteriorated by poor elevational resolution which is achieved by an acoustic lens. To overcome this limitation, we present a three-dimensional (3D) image reconstruction method using a commercial one-dimensional (1D) array transducer. METHODS: In the method, the elevational resolution is improved by applying synthetic aperture focusing (SAF) technique along the elevational direction. For this, a commercially available 1D array transducer with an acoustic lens is modeled and appropriate synthetic focusing delay that can minimize the effect of the acoustic lens is derived by mathematical analysis. RESULTS: From the simulation and experiment results, it was demonstrated that the proposed method can enhance the image quality of PA imaging, i.e., elevational resolution and signal-to-noise ratio (SNR). CONCLUSION: 3D PA images with improved elevational resolution were achieved using a clinical 1D array transducer. SIGNIFICANCE: The presented method may be useful for clinical application such as detecting microcalcification, imaging of tumor vasculature and guidance of biopsy in real time.

Effectiveness of synthetic aperture focusing and coherence factor weighting for intravascular ultrasound imaging.

Synthetic aperture focusing (SAF) and coherence factor weighting (CFW) have been used to improve the lateral resolution of ultrasound images. Although the two methods are effective for array-based ultrasound imaging, many researchers have also employed the methods for single-element-based imaging including intravascular ultrasound (IVUS) imaging. For single-element-based imaging, CFW is generally calculated from the scanlines obtained by SAF and applied to the scanline obtained after coherent summation of the SAF delayed scanlines, which is called a SAF-CFW method. In the paper, a theoretical model was derived to explore the effectiveness of SAF and CFW for single-element-based imaging, and the model was used to explain that SAF is not effective for IVUS imaging in terms of enhancing the spatial resolution, although it has the advantage of improving a contrast-to-noise ratio (CNR). This means that the SAF-CFW method is not optimal for improving the spatial resolution of IVUS imaging. In contrast, it was found in simulations and experiments that applying CFW to the target scanline itself is beneficial for the spatial resolution rather than a coherent summed scanline for IVUS SAF imaging, but CNR was not as good as SAF and SAF-CFW. As a result of both simulation and experimentation, it could be concluded that focused IVUS transducers without the application of those methods may be more advantageous to improve the spatial and contrast resolution simultaneously, considering the system complexity in the implementation of such imaging methods.

PMP(Porphyrin-Micelle-PSMA) Nanoparticles for Photoacoustic and Ultrasound Signal Amplification in Mouse Prostate Cancer Xenografts.

Photoacoustic (PA) imaging is used widely in cancer diagnosis. However, the availability of PA agents has not made great progress due to the limitations of the one currently in use, porphyrin. Porphyrin-Micelle (PM), developed by synthesizing porphyrin and PEG-3.5k, confirmed the amplification of the PA agent signal, and added binding affinity in an LNCaP model by attaching prostate-specific membrane antigen PSMA. Compared to the previously used porphyrin, a superior signal was confirmed, and the potential of PMP was confirmed when it showed a signal superior to that of hemoglobin at the same concentration. In addition, in the in vivo mouse experiment, it was confirmed that the signal in the LNCaP xenograft model was stronger than that in the PC-3 xenograft model, and the PMP signal was about three times higher than that of PM and porphyrin.

Elimination of Nontargeted Photoacoustic Signals for Combined Photoacoustic and Ultrasound Imaging.

As a molecular imaging modality, photoacoustic (PA) imaging has been in the spotlight because it can provide an optical contrast image of physiological information and a relatively deep imaging depth. However, its sensitivity is limited despite the use of exogenous contrast agents due to the background PA signals generated from nontargeted absorbers, such as blood and boundaries between different biological tissues. In addition, clutter artifacts generated in both in-plane and out-of-plane imaging region degrade the sensitivity of PA imaging. We propose a method to eliminate the nontargeted PA signals. For this study, we used a dual-modal ultrasound (US)-PA contrast agent that is capable of generating both the backscattered US and PA signals in response to the transmitted US and irradiated light, respectively. The US images of the contrast agents are used to construct a masking image that contains the location information about the target site and is applied to the PA image acquired after contrast agent injection. In vitro and in vivo experimental results demonstrated that the masking image constructed using the US images makes it possible to completely remove nontargeted PA signals. The proposed method can be used to enhance the clear visualization of the target area in PA images.

Exosome-based photoacoustic imaging guided photodynamic and immunotherapy for the treatment of pancreatic cancer.

Exosomes, which are released from all cells and take part in cell-to-cell communication, have been utilized as drug delivery vehicles in many recent studies. Immunotherapy is an emerging technology which uses patients' innate immune systems. In immunotherapy, immune cells are stimulated through antibodies, the other immune cells and genetic modifications for the purposes of, for instance, cancer therapy. In this study, tumor-derived re-assembled exosome (R-Exo) was simultaneously utilized as both a drug delivery carrier and an immunostimulatory agent. A chlorin e6 photosensitizer was loaded into tumor-derived exosomes during exosomal re-assembly. After this modification, R-Exo retains its original average size and has the same membrane proteins, which allows for targeting of tumor cells. Chlorin e6-loaded R-Exo (Ce6-R-Exo) can be visualized by photoacoustic imaging and can efficiently generate reactive oxygen species inside tumor cells under laser irradiation. In addition, Ce6-R-Exo increased the release of cytokines from immune cells, which indicates that these modified exosomes can be used as an immunotherapeutic agent. In conclusion, we developed a novel strategy that enables photoacoustic imaging-guided photodynamic and immune-combination therapy for the treatment of cancer with tumor-derived Ce6-R-Exo.

Forward-Looking Multimodal Endoscopic System Based on Optical Multispectral and High-Frequency Ultrasound Imaging Techniques for Tumor Detection.

We developed a forward-looking (FL) multimodal endoscopic system that offers color, spectral classified, high-frequency ultrasound (HFUS) B-mode, and integrated backscattering coefficient (IBC) images for tumor detection in situ. Examination of tumor distributions from the surface of the colon to deeper inside is essential for determining a treatment plan of cancer. For example, the submucosal invasion depth of tumors in addition to the tumor distributions on the colon surface is used as an indicator of whether the endoscopic dissection would be operated. Thus, we devised the FL multimodal endoscopic system to offer information on the tumor distribution from the surface to deep tissue with high accuracy. This system was evaluated with bilayer gelatin phantoms which have different properties at each layer of the phantom in a lateral direction. After evaluating the system with phantoms, it was employed to characterize forty human colon tissues excised from cancer patients. The proposed system could allow us to obtain highly resolved chemical, anatomical, and macro-molecular information on excised colon tissues including tumors, thus enhancing the detection of tumor distributions from the surface to deep tissue. These results suggest that the FL multimodal endoscopic system could be an innovative screening instrument for quantitative tumor characterization.

Magnetically Actuated Forward-Looking Interventional Ultrasound Imaging: Feasibility Studies.

OBJECTIVE: Interventional ultrasound imaging is a prerequisite for guiding implants and treatment within the hearts and blood vessels. Due to limitations on the catheter's diameter, interventional ultrasonic transducers have side-looking structures although forward-looking imaging may provide more intuitive and real time guidance in treating diseased sites ahead of catheters. To address the issue, a magnetically actuated forward-looking interventional ultrasound imaging device is implemented for the first time. METHODS: A forward-looking catheter containing a 1 mm ring type focused 35 MHz ultrasound transducer and a micro magnet, was fabricated. For imaging, the transducer was placed at the center of four electromagnetic coils positioned on four sides of a squared acrylic housing. By modifying the magnetic field, the catheter tip could be remotely translated for sector scanning. RESULTS: The scanning angle could reach up to 3° in 1 Hz with 15 mT, while wider angles of 5° could be achieved with a higher magnetic field of 25 mT for ex-vivo imaging. The position of the transducer could be detected by monitoring the motion with a CCD camera, mimicking clinical X-ray imaging. In the wire target and tissue mimicking phantom studies, the measured hole size, spatial resolution and distance between wires by the proposed system were comparable with the values from a linear scanner. Multi-frame real time data acquisition was demonstrated via ex-vivo imaging on a pig's coronary artery. CONCLUSION/SIGNIFICANCE: The feasibility of magnetically actuated forward-looking interventional ultrasound imaging was demonstrated. The remote-controlled scanning method may allow to simplify the structures of forward-looking interventional ultrasound imaging catheters.

Visibility of Bioresorbable Vascular Scaffold in Intravascular Ultrasound Imaging.

Bioresorbable vascular scaffold (BVS) has recently been spotlighted for its unique characteristics of absorbing into blood vessels and eventually disappearing. Although intravascular ultrasound (IVUS) is the most common guiding tool for stent deployment, the echogenicity of BVS struts has changed as the center of stent lumen and scanning rotation is not concentric, which may cause a critical erroneous measurement in practice. This study investigated the physical conditions for dimming the stent brightness in IVUS images using a finite-difference method (FDM) to numerically solve acoustic wave propagation through nonhomogeneous medium. The dimmed brightness is caused by an angled rectangular cross section of a strut and its similar acoustic impedance with water. Imaging frequency is not a major cause. However, the angle between the acoustic beam and the BVS surface is the major cause of the dimmed brightness. As a solution, an approach using a frequency compounding method with signal polarity comparator was proposed to recover the reduced brightness without sacrificing spatial resolutions. Based on the simulation study, the signal level from BVS can be attenuated down by 17 dB when the angle between the acoustic beamline and the surface of BVS is more than 45°. With the proposed frequency compounding approach, the reduced signal can be recovered by 6 dB. In the experimental BVS IVUS imaging, strut brightness was reduced by 18 dB with an angled strut position and recovered by 5 dB with the proposed frequency compounding method. A pig coronary was imaged to demonstrate the performance of the proposed method.

Dual-Element Intravascular Ultrasound Transducer for Tissue Harmonic Imaging and Frequency Compounding: Development and Imaging Performance Assessment.

OBJECTIVE: For accurate diagnosis of atherosclerosis, the high spatial and contrast resolutions of intravascular ultrasound (IVUS) images are a key requirement. Increasing the center frequency of IVUS is a simple solution to meet this requirement. However, this leads to a reduction in imaging depth due to the frequency-dependent attenuation of ultrasound. Here, we report a recently developed dual-element IVUS transducer for tissue harmonic imaging (THI) and frequency compounding to increase the spatial and contrast resolutions of IVUS images, while maintaining the imaging depth to assess the overall morphological change of blood vessels. METHODS: One 35-MHz element is used for producing general IVUS images and the other 70-MHz element is for receiving the second harmonic signals induced by the 35-MHz ultrasound. The fundamental and second harmonic signals can also be used for frequency compound imaging to further improve contrast resolution. The spatial and contrast resolutions achieved by the developed transducer were evaluated through wire and tissue-mimicking phantom imaging tests. Additionally, the images of a stent deployed in a tissue-mimicking phantom and an excised pig artery were acquired to assess clinical usefulness of the transducer. RESULTS: The results demonstrated that the developed IVUS transducer enables us to simultaneously examine the overall morphological change of blood vessels by the 35-MHz ultrasound images and the near vessel layers such as the intima, the media, and the adventitia by either THI or compound images with high spatial and contrast resolutions. In addition, the developed transducer facilitates the simultaneous acquisition of 35- and 70-MHz fundamental images when needed. CONCLUSION: The developed dual-element IVUS transducer makes it possible to fully realize the potential benefits of IVUS in the diagnosis of atherosclerosis.