High Frequency Ultrasound Imaging Research Articles

Bipolar-power-transistor-based limiter for high frequency ultrasound imaging systems

High performance limiters are described in this paper for applications in high frequency ultrasound imaging systems. Limiters protect the ultrasound receiver from the high voltage (HV) spikes produced by the transmitter. We present a new bipolar power transistor (BPT) configuration and compare its design and performance to a diode limiter used in traditional ultrasound research and one commercially available limiter. Limiter performance depends greatly on the insertion loss (IL), total harmonic distortion (THD) and response time (RT), each of which will be evaluated in all the limiters. The results indicated that, compared with commercial limiter, BPT-based limiter had less IL (−7.7dB), THD (−74.6dB) and lower RT (43ns) at 100MHz. To evaluate the capability of these limiters, they were connected to a 100MHz single element transducer and a two-way pulse-echo test was performed. It was found that the −6dB bandwidth and sensitivity of the transducer using BPT-based limiter were better than those of the commercial limiter by 22% and 140%, respectively. Compared to the commercial limiter, BPT-based limiter is shown to be capable of minimizing signal attenuation, RT and THD at high frequencies and is thus suited for high frequency ultrasound applications.

Novel power MOSFET-based expander for high frequency ultrasound systems

The function of an expander is to obstruct the noise signal transmitted by the pulser so that it does not pass into the transducer or receive electronics, where it can produce undesirable ring-down in an ultrasound imaging application. The most common type is a diode-based expander, which is essentially a simple diode-pair, is widely used in pulse-echo measurements and imaging applications because of its simple architecture. However, diode-based expanders may degrade the performance of ultrasonic transducers and electronic components on the receiving and transmitting sides of the ultrasound systems, respectively. Since they are non-linear devices, they cause excessive signal attenuation and noise at higher frequencies and voltages. In this paper, a new type of expander that utilizes power MOSFET components, which we call a power MOSFET-based expander, is introduced and evaluated for use in high frequency ultrasound imaging systems. The performance of a power MOSFET-based expander was evaluated relative to a diode-based expander by comparing the noise figure (NF), insertion loss (IL), total harmonic distortion (THD), response time (RT), electrical impedance (EI) and dynamic power consumption (DPC). The results showed that the power MOSFET-based expander provided better NF (0.76dB), IL (−0.3dB) and THD (−62.9dB), and faster RT (82ns) than did the diode-based expander (NF (2.6dB), IL (−1.4dB), THD (−56.0dB) and RT (119ns)) at 70MHz. The −6dB bandwidth and the peak-to-peak voltage of the echo signal received by the transducer using the power MOSFET-based expander improved by 17.4% and 240% compared to the diode-based expander, respectively. The new power MOSFET-based expander was shown to yield lower NF, IL and THD, faster RT and lower ring down than the diode-based expander at the expense of higher dynamic power consumption.

SU-E-U-11: Deformable Registration of CT and Ultrasound Images for Radiation Treatment of Skin Cancer

Purpose: High-frequency ultrasound (HFUS) images capable of revealing accurate spatial information in skin lesions may be used to plan and guide radiation therapy (RT) for skin cancer. In this work, we develop a method for deformable image registration of ultrasound and CT images for skin cancer RT. Methods: Skin lesion images acquired with HFUS and the corresponding CTs were registered in the regions of interest. A correspondence function was used to map attenuation values to tumor elasticity and a histogram matching was implemented. A novel DIR technique, based on the symmetric force Demons algorithm, was used in which the size of the Gaussian smoothing kernel was adaptively adjusted. The Pearson correlation coefficient (PCC) was used to assess the registration accuracy. Results: Observed PCC values of 0.9794 and 0.9815 (enhanced contrast) indicated excellent agreement between the dynamic (HFUS) and static (CT) images. The technique exhibited an ability to process large deformations as ROI displacement exceeding tumor thickness was observed near the edges of the lesion. The gradual decrease of kernel dimension was found to prevent non-physical warping, thereby improving registration accuracy. This robustness is critical to skin cancer RT as tumors may shrink significantly during treatment. Run times averaged 3.26 seconds per fraction. Conclusion: Combined with image processing techniques, the proposed method is sufficiently accurate for deformable registration of HFUS and CT images for skin cancer RT. The ability to perform image-guided treatment for skin cancer could reduce the number of biopsies needed during tumor excision and could spare healthy tissue. The presented technique is accurate and robust enough to process large deformations, making it a promising tool for RT planning and delivery guidance for skin cancer.

Do High Frequency Ultrasound Images Support Clinical Skin Assessment?

High frequency ultrasound imaging has been reported as a potential method of identifying the suspected tissue damage in patients “at risk” of pressure ulceration. The aim of this study was to explore whether ultrasound images supported the clinical skin assessment in an inpatient population through identification of subcutaneous tissue damage. Skin on the heels and/or sacral coccygeal area of fifty vascular surgery inpatients was assessed clinically by tissue viability nurses and with ultrasound pre operatively and at least every other day until discharge. Images were compared to routine clinical skin assessment outcomes. Qualitative classification of ultrasound images did not match outcomes yielded through the clinical skin assessment. Images corresponding to 16 participants were classified as subgroup 3 damage at the heels (equivalent to grade 2 pressure ulceration); clinical skin assessment rated no heels as greater than grade 1a (blanching erythema). Conversely, all images captured of the sacral coccygeal area were classified as normal; the clinical skin assessment rated two participants as grade 1b (non-blanching erythema). Ultrasound imaging is a potentially useful adjunct to the clinical skin assessment in providing information about the underlying tissue. However, further longitudinal clinical assessment is required to characterise images against actual and “staged” pressure ulceration.

Murine Fetal Echocardiography

Transgenic mice displaying abnormalities in cardiac development and function represent a powerful tool for the understanding the molecular mechanisms underlying both normal cardiovascular function and the pathophysiological basis of human cardiovascular disease. Fetal and perinatal death is a common feature when studying genetic alterations affecting cardiac development. In order to study the role of genetic or pharmacologic alterations in the early development of cardiac function, ultrasound imaging of the live fetus has become an important tool for early recognition of abnormalities and longitudinal follow-up. Noninvasive ultrasound imaging is an ideal method for detecting and studying congenital malformations and the impact on cardiac function prior to death. It allows early recognition of abnormalities in the living fetus and the progression of disease can be followed in utero with longitudinal studies. Until recently, imaging of fetal mouse hearts frequently involved invasive methods. The fetus had to be sacrificed to perform magnetic resonance microscopy and electron microscopy or surgically delivered for transillumination microscopy. An application of high-frequency probes with conventional 2-D and pulsed-wave Doppler imaging has been shown to provide measurements of cardiac contraction and heart rates during embryonic development with databases of normal developmental changes now available. M-mode imaging further provides important functional data, although, the proper imaging planes are often difficult to obtain. High-frequency ultrasound imaging of the fetus has improved 2-D resolution and can provide excellent information on the early development of cardiac structures.

Development of a Bipolar Pulse Generator for High-Frequency Ultrasound Imaging System

The pulse generator is the critical component in high-frequency ultrasound imaging systems. Currently, there still exist some shortcomings about commercial ultrasound image systems and devices such as 5900 PR …etc.. However, to achieve a higher sensitivity and high performance, a programmable pulser generator is desired to match the requirements of high frequency ultrasound image system. In this study, we utilized a novel bipolar pulse generator method to overcome those issues in developed high resolution image system. As the needs of application in clinic, a real –time of high-frequency ultrasound imaging systems, including pulse generator, high speed scanning mechanism, high voltage protection and FPGA trigger control circuit, was developed in our Laboratory. This paper will focus to compare the performance of the bipolar generator and unipolar generator as used in pulse generator device respectively. Finally, the developed bipolar pulse generator show the better performance than the unipolar generator does. The bipolar system can generate clean N-cycle bipolar pulses and improve the center frequency of transducer up to 60 MHz. The axial resolution of scan system has been improved to around 60 μm. In addition, the result indicated that the proposed bipolar pulser could increase 4 dB for pulse/echo waveforms amplitude.

Non-invasive characterization of polyurethane-based tissue constructs in a rat abdominal repair model using high frequency ultrasound elasticity imaging

The evaluation of candidate materials and designs for soft tissue scaffolds would benefit from the ability to monitor the mechanical remodeling of the implant site without the need for periodic animal sacrifice and explant analysis. Toward this end, the ability of non-invasive ultrasound elasticity imaging (UEI) to assess temporal mechanical property changes in three different types of porous, biodegradable polyurethane scaffolds was evaluated in a rat abdominal wall repair model. The polymers utilized were salt-leached scaffolds of poly(carbonate urethane) urea, poly(ester urethane) urea and poly(ether ester urethane) urea at 85% porosity. A total of 60 scaffolds (20 each type) were implanted in a full thickness muscle wall replacement in the abdomens of 30 rats. The constructs were ultrasonically scanned every 2 weeks and harvested at weeks 4, 8 and 12 for compression testing or histological analysis. UEI demonstrated different temporal stiffness trends among the different scaffold types, while the stiffness of the surrounding native tissue remained unchanged. The changes in average normalized strains developed in the constructs from UEI compared well with the changes of mean compliance from compression tests and histology. The average normalized strains and the compliance for the same sample exhibited a strong linear relationship. The ability of UEI to identify herniation and to characterize the distribution of local tissue in-growth with high resolution was also investigated. In summary, the reported data indicate that UEI may allow tissue engineers to sequentially evaluate the progress of tissue construct mechanical behavior in vivo and in some cases may reduce the need for interim time point animal sacrifice.

The use of high frequency ultrasound imaging in skin moisturization measurement

The appropriate skin hydration level enables its normal function and healthy appearance. The purpose of present research was to assess the applicability of high frequency ultrasound (HFU) to the monitoring of skin moisturization treatments. The study sample encompassed 27 women, aged 20-67 y.o. (mean age of 45.48 y.o.) with dry skin. All women applied a strong moisturizing cream on their facial skin for 14days. The course of treatment was monitored using the HFU. The following parameters were subjected to the ultrasound evaluation: epidermal echo thickness, dermis thickness, and separately the thickness of the superior and inferior layer of dermis. The measurements were taken on the participants' chins and cheeks. In addition, skin hydration and transepidermal water loss (TEWL) were determined. Statistically significant differences were obtained between the echogenicity of the superior layer of the dermis on the chin and cheek. After treatment, the statistically significant values of TEWL decrease and hydration increase were obtained on the cheek skin. No statistically significant differences between the TEWL or hydration levels were found on the chin. No statistically significant differences between the epidermal echo and dermis thickness values for the two measurement points were observed. The HFU is a useful method for the monitoring of skin moisturization treatments.

Conservative Surgical Approach for Reduction of Macrocheilitis Caused by Massive Injection of Liquid Silicone

Cosmetic lip augmentation, regardless of the filling agent, is nowadays one of the most requested aesthetic procedures. Liquid silicone injections were used in the past, but after reports of severe late complications their use has been discontinued, ending with a permanent ban in most western countries. In this report we describe clinical presentation, diagnostic pathways and surgical reconstruction of six patients presenting with macrocheilia due to previous liquid silicone augmentation. Patients showed chronic inflammation of the lower third of the face, lip eversion, various degrees of asymmetry and functional impairment of the lips. All patients underwent preoperative soft tissue High Frequency Ultrasound (HFUS) and Magnetic Resonance Imaging (MRI) of the of the face to obtain evidence of the filler material and to ascertain its diffusion within the soft tissues of the perioral region. Conservative surgery was carried out to remove foreign material and to restore symmetric aesthetically pleasing lips. Histology confirmed the siliconoma diagnosis. HFUS and RMI allowed to clearly identify the silicone within the soft tissues. The conservative surgery restored the harmonious relationship between the lips, with an improvement in lip functionality at long term follow-up. Healing was complete and uneventful in all of the patients.

Current Status and New Developments in Breast Cancer Diagnosis and Detection

Despite extensive research into new ways of imaging the breast x-ray mammography and breast ultrasound, supplemented where necessary by magnetic resonance imaging, remain the techniques used for the vast majority of breast imaging for screening and the assessment of symptomatic breast problems. Recent advances in these technologies mean that these three techniques are highly effective for both detecting disease and for confirming normality. X-ray based imaging of the breast has been around now for 100 years but it is only in the last 10 years or so that digital technology developments have allowed for major advances in the efficacy of this technique. Digital breast tomosynthesis is currently the most promising technology as it has the potential to both improve detection of breast cancer and greatly reduce the numbers of false positive events. Technological advances in grey scale high frequency ultrasound imaging mean that it is now universally used in both symptomatic diagnosis and breast screening. Newer ultrasound techniques such as 3D imaging, Doppler analyses and elastography add some additional value but so far none of these has achieved their hoped for additional potential. Magnetic resonance imaging is currently the most sensitive imaging technique for the detection and characterisation of breast disease, but its cost remains a barrier to its more widespread use. Nuclear medicine techniques have a role is special circumstances but are yet to show that they should be used in routine practice. There are a large number of potential alternative new imaging techniques for the breast, but, as yet, none of these have shown any significant benefits over the current techniques. Dedicated breast computed tomography has perhaps the best promise but clinically effective breast imaging at present remains in the application and refinement of recent developments in digital mammography, ultrasound and magnetic resonance imaging.

Optimization of Acoustic Liposomes for Improved In Vitro and In Vivo Stability

Liposomes encapsulating perfluoropropane gas, termed acoustic liposomes (ALs), which can serve both for ultrasound (US) imaging and US-mediated gene delivery, have been reported. However, the echogenicity of ALs decreases within minutes in vivo due to gas diffusion and leakage, hindering time-consuming procedures such as contrast-enhanced 3D US imaging and raising the need for improvement of their stability. The stability of ALs preparations incorporating increasing ratios of anionic / unsaturated phospholipids, polyethylene glycol (PEG)ylated phospholipid and cholesterol was investigated by measurement of their reflectivity over time using a high-frequency US imaging system, both in vitro and in vivo. The retention of echogenicity of ALs in vitro is enhanced with increasing molar ratios of PEGylated lipids. Addition of 10 molar percent of an anionic phospholipid resulted in a 31% longer half-life, while cholesterol had the opposite effect. Assessment of the stability of an optimized composition showed a more than 2-fold increase of the detection half-life in mice. Presence of a PEG coating not only serves to provide "stealth" properties in vivo, but also contributes to the retention of the encapsulated gas. The optimized ALs reported here can be used as a contrast agent for lengthier imaging procedures.

High-frequency rapid B-mode ultrasound imaging for real-time monitoring of lesion formation and gas body activity during high-intensity focused ultrasound ablation

The goal of this study was to examine the ability of high-frame-rate, high-resolution imaging to monitor tissue necrosis and gas-body activities formed during high-intensity focused ultrasound (HIFU) application. Ex vivo porcine cardiac tissue specimens (n = 24) were treated with HIFU exposure (4.33 MHz, 77 to 130 Hz pulse repetition frequency (PRF), 25 to 50% duty cycle, 0.2 to 1 s, 2600 W/cm(2)). RF data from B-mode ultrasound imaging were obtained before, during, and after HIFU exposure at a frame rate ranging from 77 to 130 Hz using an ultrasound imaging system with a center frequency of 55 MHz. The time history of changes in the integrated backscatter (IBS), calibrated spectral parameters, and echo-decorrelation parameters of the RF data were assessed for lesion identification by comparison against gross sections. Temporal maximum IBS with +12 dB threshold achieved the best identification with a receiver-operating characteristic (ROC) curve area of 0.96. Frame-to-frame echo decorrelation identified and tracked transient gas-body activities. Macroscopic (millimeter-sized) cavities formed when the estimated initial expansion rate of gas bodies (rate of expansion in lateral-to-beam direction) crossed 0.8 mm/s. Together, these assessments provide a method for monitoring spatiotemporal evolution of lesion and gas-body activity and for predicting macroscopic cavity formation.

High-Resolution Ultrasound Imaging of Human Skin In Vivo by Using Three-Dimensional Ultrasound Microscopy

Observing the morphology of human skin is important in the diagnosis of skin cancer and inflammation and in the assessment of skin aging. High-frequency ultrasound imaging provides high spatial resolution of the deep layers of the skin, which cannot be visualized by optical methods. The objectives of the present study were to develop a three-dimensional (3-D) ultrasound microscope and to observe the morphology of normal human skin in vivo. A concave polyvinylidene fluoride transducer with a central frequency of 120 MHz was excited using an electric pulse generated by semiconductor switching. The transducer was scanned two-dimensionally by using two linear motors on the region-of-interest and the ultrasonic reflection was digitized with 2-GHz sampling. Consecutive B-mode images perpendicular to the skin surface were reconstructed to generate multiplanar reconstructed images and 3-D volume-rendering images clearly showing microstructures such as sebaceous glands and hair follicles. The 3-D ultrasound microscope could be used to successfully image the morphology of human skin noninvasively and may provide important information on skin structure.

Detection of changes of scar thickness under mechanical loading using ultrasonic measurement

The intervention of pressure therapy on management of hypertrophic scar (HS) after burn is based on the theoretical assumption that the mechanical force added onto the scar tissue will reduce the growth of myofibroblasts which create the collagen clusters and the interstitial space, and to realign fibrous tissues, thus reducing the thickness of HS. In this experimental study, a high frequency ultrasound imaging system (12MHz) was applied to measure the real time changes of thickness of the post burn HS under a mechanical loading system with similar pressure generated to the scar tissue. The validity of the ultrasound system in measurement of the changes of scar thickness underneath the tissue was tested on the porcine skin in vitro followed by measurement of human skin in vivo. Results showed that the ultrasound measurement of thickness had both good validity (r2=0.98, p<0.0001) and good intra-rater reliability (ICC=0.89). Then, the system was used to test the thickness of 14 human HS samples in vivo among 7 subjects. External loading force with similar pressure range (10–45mmHg) was then applied to these scar samples via ultrasound probe with rectangular contacting area at 4cm2 and each loading force was maintained unchange for 2min over the scar tissue. The real time scar thickness was documented. Results showed that the mean scar thickness was found to be significantly decreased when the loading force applied was increased from 5 to 35mmHg (with 10mmHg interval) (p<0.001). A significant negative correlation between the pressure level and scar thickness was observed (r2=0.96, p=0.005). The decline of thickness was found more significant between 0mmHg and 15mmHg. The findings were in line with the postulate that pressure therapy is effective in reducing the thickness of HS. A long term followup study should be administered to determine the prolonged effect of pressure intervention.

A multifunctional, reconfigurable pulse generator for high-frequency ultrasound imaging

High-frequency (>20 MHz) ultrasound (HFUS) imaging systems have made it possible to image small structures with fine spatial resolution. They find a variety of biomedical applications in dermatology, ophthalmology, intravascular imaging, and small-animal imaging. One critical technical challenge of HFUS is to generate high-voltage, high-frequency pulsed signals to effectively excite the transducer for a high SNR. This paper presents the development of a multifunctional, reconfigurable pulse generator for HFUS imaging. The pulse generator can produce a high-voltage unipolar pulse, a bipolar pulse, or arbitrary pulses for B-mode imaging, Doppler measurement, and modulated excitation imaging. The characteristics of the pulses, such as timing, waveform, and frequency are reconfigurable by a high-speed field-programmable gate array (FPGA). Customized software was developed to interface with the FPGA through a USB connector for pulse selection, and easy, flexible, real-time pulse management. The hardware was implemented in a compact, printed circuit board (PCB)-based scheme using state-of-the-art electronics for costeffectiveness and fully digital control. Testing results show that the unipolar pulse can reach over 165 Vpp with a 6-dB bandwidth of 70 MHz, and the bipolar pulse and arbitrary pulses can reach 150 and 60 Vpp with central frequencies of 60 and 120 MHz, respectively.

Modeling Human Choroidal Melanoma Xenograft Growth in Immunocompromised Rodents to Assess Treatment Efficacy

To evaluate potential treatments of primary uveal melanoma in rodent xenograft models, it is necessary to track individual tumor growth during treatment. Previously, high-frequency ultrasound (HF-US) was used to measure tumor volume in nude rats for up to 2 weeks. This study tests the hypothesis that HF-US can be used to repeatedly measure tumor volume for at least a month in both nude rat and severe combined immunodeficiency (SCID) mouse xenograft models of human uveal melanoma, with the goal of modeling tumor growth to evaluate treatment efficacy. C918 human uveal melanoma spheroids were implanted in the choroids of six nude rats and six severe combined immunodeficiency mice. OCM-1 human uveal melanoma spheroids were implanted in six nude rats. Every 4-7 days thereafter for up to 5 weeks, HF-US images of the tumor-bearing eye were captured every 100 or 250 μm. Tumor areas were measured on each image and integrated to calculate volume. Tumor growth was modeled using a logistic curve, and parameters characterizing growth, including the time to reach a target volume (t(T)), were evaluated as potential measures of treatment efficacy. Tumor volume could be measured for up to 5 weeks in all models, and the logistic curve described the growth well. The parameter t(T) was shown to be a suitable endpoint to evaluate treatments. HF-US is a practical method to track uveal melanoma growth in the same nude rat or SCID mouse for up to a month. Such growth data can be used to evaluate treatments in these xenograft models.

High frequency ultrasound imaging of whole blood gelation and retraction during in vitro coagulation

Blood coagulation is a series of biochemical reactions resulting in the mechanical transformation of liquid blood into a gel. As a consequence, ultrasound, being mechanical waves, can provide specific details on the dynamics of coagulation. In fact, previous high-frequency ultrasound monitoring studies have shown drastic changes in ultrasound velocity and attenuation during whole blood coagulation and a model discussing the observed mechanical transformations was proposed. In this paper, a technique of visualization of the clotting mechanism is introduced, which complements and revises the previous hypotheses. This method is based on the monitoring of scatterers (red blood cells) movement through a time correlation of 20 MHZ rf signals. It allows the computing of both a displacement map revealing local details and disparities and a parameter quantifying the global structural behavior. Qualitative results for two typical samples show that the technique provides new insights on the gelation dynamics. A quantitative analysis computed from 12 healthy subjects found that the changes in the structural parameters are significantly correlated to the changes in velocity and attenuation, both dependent on the mechanical transformations in the sample. The previous model is therefore revised and a new way to measure gel and retraction times is proposed.

Application of optical coherence tomography and high-frequency ultrasound imaging during noninvasive laser vasectomy

A noninvasive approach to vasectomy may eliminate male fear of complications related to surgery and increase its acceptance. Noninvasive laser thermal occlusion of the canine vas deferens has recently been reported. Optical coherence tomography (OCT) and high-frequency ultrasound (HFUS) are compared for monitoring laser thermal coagulation of the vas in an acute canine model. Bilateral noninvasive laser coagulation of the vas was performed in six dogs (n=12 vasa) using a Ytterbium fiber laser wavelength of 1075 nm, incident power of 9.0 W, pulse duration of 500 ms, pulse rate of 1 Hz, and 3-mm-diameter spot. Cryogen spray cooling was used to prevent skin burns during the procedure. An OCT system with endoscopic probe and a HFUS system with 20-MHz transducer were used to image the vas immediately before and after the procedure. Vasa were then excised and processed for gross and histologic analysis for comparison with OCT and HFUS images. OCT provided high-resolution, superficial imaging of the compressed vas within the vas ring clamp, while HFUS provided deeper imaging of the vas held manually in the scrotal fold. Both OCT and high HFUS are promising imaging modalities for real-time confirmation of vas occlusion during noninvasive laser vasectomy.

Multimodality Imaging In Vivo for Preclinical Assessment of Tumor-Targeted Doxorubicin Nanoparticles

This study presents a new multimodal imaging approach that includes high-frequency ultrasound, fluorescence intensity, confocal, and spectral imaging to improve the preclinical evaluation of new therapeutics in vivo. Here we use this approach to assess in vivo the therapeutic efficacy of the novel chemotherapy construct, HerDox during and after treatment. HerDox is comprised of doxorubicin non-covalently assembled in a viral-like particle targeted to HER2+ tumor cells, causing tumor cell death at over 10-fold lower dose compared to the untargeted drug, while sparing the heart. Whereas our initial proof-of-principle studies on HerDox used tumor growth/shrinkage rates as a measure of therapeutic efficacy, here we show that multimodal imaging deployed during and after treatment can supplement traditional modes of tumor monitoring to further characterize the particle in tissues of treated mice. Specifically, we show here that tumor cell apoptosis elicited by HerDox can be monitored in vivo during treatment using high frequency ultrasound imaging, while in situ confocal imaging of excised tumors shows that HerDox indeed penetrated tumor tissue and can be detected at the subcellular level, including in the nucleus, via Dox fluorescence. In addition, ratiometric spectral imaging of the same tumor tissue enables quantitative discrimination of HerDox fluorescence from autofluorescence in situ. In contrast to standard approaches of preclinical assessment, this new method provides multiple/complementary information that may shorten the time required for initial evaluation of in vivo efficacy, thus potentially reducing the time and cost for translating new drug molecules into the clinic.

High resolution biomedical imaging—multimodal ultrasound microscope and combination with optics

High frequency ultrasound imaging has evolved from classical acoustic microscopy to the multimodal ultrasound microscope which is available for quantitative C-mode, surface acoustic impedance mode and 3D-mode imaging. The evolution has realized both quantitative parametric imaging and easier observation. Quantitative C-mode representing two-dimensional distribution of attenuation or sound speed is realized by frequency-domain analysis of a single pulse by a high speed digitizer. Because the square of sound speed is proportional to the tissue elasticity, sound speed imaging provides biomechanical information of the tissues which is especially important in cardiology and orthopedic surgery. The data also help understanding clinical echo features, especially important in grading of liver fibrosis. Surface acoustic impedance mode without thin-slicing has been applied for imaging of fresh brain tissues and real time observation of high-intensity focused ultrasound procedures. High frequency 3D-mode imaging has visualized 3D structure of sebaceous gland in dermis. Compared with optical coherence tomography which provides higher resolution imaging, ultrasound is superior in the penetration depth and assessment of tissue elasticity. Photoacoustic imaging provides not only morphology but also small blood flow distribution. Both ultrasound and optical methods should develop together to realize high resolution and “gentle” biomedical imaging.