Harmonic intravascular ultrasound imaging with a dual-frequency catheter

Recent studies have shown the feasibility of tissue and contrast harmonic imaging with a prototype nonlinear intravascular ultrasound (IVUS) system using a conventional single-element rotating IVUS catheter. In this study, a dual-frequency transducer element was mounted in an IVUS catheter and its second harmonic imaging performance was investigated and compared with that of a conventional IVUS catheter. Hydrophone measurements showed a transmit efficiency improvement of >6 dB for the dual-frequency catheter at 20 MHz. In vitro phantom experiments showed a signal-to noise ratio improvement of >5 dB in second harmonic mode at 40 MHz (H40) with the dual-frequency catheter, when using equal transmit voltage for both catheters. Finally, in vivo experiments were conducted and showed image improvement in H40 acquisitions with respect to the conventional IVUS catheter.     

Nonlinear intravascular ultrasound contrast imaging

Nonlinear contrast agent imaging with intravascular ultrasound (IVUS) is investigated using a prototype IVUS system and an experimental small bubble contrast agent. The IVUS system employed a mechanically scanned single element transducer and was operated at a 20 MHz transmit frequency (F20) for second harmonic imaging (H40), and at a 40 MHz transmit frequency (F40) for subharmonic imaging (SH20). Characterization experiments were performed with agent and tissue phantom signals acquired during transducer rotation. The suppression of transmit frequency tissue signals was achieved using a combination of pulse-inversion and bandpass filtering. H40 was found to improve the contrast-to-tissue signal ratio (CTR) by up to 22 dB relative to F20, but suffered from tissue propagation harmonics at higher pressures (>0.3 MPa). SH20 was also shown to be possible at a range of pressures (approximately 0.25 to 1.8 MPa), with tissue signals suppressed to near the noise floor. Coronary phantom experiments demonstrated the detection of agent in 1 mm diameter vessels outside a larger 4 mm diameter vessel in which the IVUS catheter was situated. These results suggest the feasibility of harmonic IVUS contrast imaging, which may have applications in coronary lumen boundary detection and vasa vasorum imaging.     

Experimental characterization of fundamental and second harmonic beams for a high-frequency ultrasound transducer

In the diagnostic frequency range, nonlinear imaging has been shown to improve image contrast and decrease artefacts. The extension of these techniques to high-frequency imaging (>15 MHz) was investigated. The second harmonic beam at 40 MHz of a high-frequency focused transducer (aperture 6 mm, focal distance 10 mm, f-number 1.67) was measured experimentally in water, in transmission and pulse-echo, and compared with the fundamental beams at 20 MHz and 40 MHz. Measurements were performed at peak negative pressures of 0.8 to 4.7 MPa. Transmission measurements were performed with a custom hydrophone with a 25microm spot size to limit beam averaging. Over the range of peak negative pressures, the transmitted harmonic (40 MHz) beam had an average lateral beam width (-3 dB) of 77 microm and an average depth-of-field of 0.93 mm, whereas the fundamental beam had a corresponding beam width of 137 microm and a depth-of-field of 1.59 mm. The harmonic beam showed a 3-dB decrease in side lobe levels. Preliminary second harmonic images of mouse tissue in vitro are presented and compared to fundamental imaging at 20 and 40 MHz.     

Subharmonic contrast intravascular ultrasound for vasa vasorum imaging

The feasibility of subharmonic contrast intravascular ultrasound (IVUS) imaging was investigated using a prototype nonlinear IVUS system and the commercial contrast agent Definity™. The system employed a mechanically scanned commercial catheter with a custom transducer element fabricated to have sensitivity at both 15 and 30 MHz. Experiments were conducted at a fundamental frequency of 30 MHz (F30; 25% bandwidth), with on-axis pressures ranging from 0.12 to 0.79 MPa, as measured with a needle hydrophone. In vitro characterization experiments demonstrated the detection of 15 MHz subharmonic signals (SH15) when pressure levels reached 360 kPa. The formation of SH15 images was shown, with tissue signals suppressed to near the noise floor and contrast to tissue ratios were improved by up to 30 dB relative to F30. In vivo experiments were performed using the atherosclerotic rabbit aorta model. Following the bolus injection of contrast agent upstream of the imaging catheter, agent was detected within the aorta, vena cava and within the perivascular space. These results provide a first in vivo demonstration of subharmonic contrast IVUS and suggest its potential as a new technique for imaging vasa vasorum. (E-mail: goertz@sri.utoronto.ca)     

Enhanced methods for visualizing myocardial perfusion with peripheral venous injection of Levovist®: Application of triggered harmonic imaging and triggered harmonic power Doppler imaging techniques

Objectives:The purpose of this study was to determine whether triggered harmonic imaging (THI) or triggered harmonic power Doppler imaging (THPDI) could obtain the myocardial contrast enhancement using peripheral venous injection of a first generation echocardiographic contrast agent, Levovist^®. Methods:In a phantom model, we examined the influence of an acoustic power, harmonic filters, transmitted frequencies and focus positions of transducer on Levovist^®. Then fundamental, harmonic or harmonic power Doppler imaging were performed with ECG-triggered imaging in eight closed-chest dogs using bolus injection of Levovist^®. Results:In a phantom model, the highest transmission power (Mechanical index 1.6), a medium harmonic filter and a focus position (6 cm) resulted in the best enhanced contrast in both THI and THPDI. Furthermore, higher pulse repetition frequency (5500 Hz) of harmonic power Doppler made clearer enhancement. In animal models, we could not observe the apparent myocardial contrast using triggered fundamental imaging, and the intensity of each region of interest (ROI) of myocardium had not changed significantly. However, homogeneous myocardial contrast could be obtained using THI, which was conditioned on the highest transmission power, a medium harmonic filter same as the phantom model, at a lower transmitted frequency (1.8 MHz) and a focus position, which were located in the middle portion of the left ventricle. The peak intensity of each ROI increased significantly in a gray level. Furthermore, THPDI caused emphasized myocardial contrast visually. Conclusions:These results indicate that THI and THPDI produce obvious MCE using peripheral venous injection of Levovist^®.     

Contrast harmonic transesophageal echocardiography: a feasibility study

Ultrasound (US) contrast agents serve as tracers for the noninvasive quantification of blood flow, and many of them are now approved for left ventricular opacification and for enhanced endocardial border delineation. The availability of more stable contrast bubbles has stimulated many new classes of imaging methods, such as harmonic imaging, which is already employed in commercial systems for transthoracic imaging. However, transesophageal echocardiography (TEE) still lacks appropriate technology, mainly transducer technology, to be able to take advantage of contrast harmonic benefits. We investigate, in this study, a new TEE transducer that has a frequency bandwidth wide enough to be able transmit at a lower fundamental frequency and to receive the second harmonic frequency. The transducer characteristics are measured, as well as the optimal transmit settings that allow the achievement of a high contrast-to-tissue ratio. The transducer has a center frequency of 3.5 MHz with a bandwidth ranging from 2.3 MHz to 3.9 MHz. For optimal harmonic imaging, transmit settings consisted of a transmit pulse at 2.5 MHz containing two periods. The transducer, using these settings, was then evaluated in patients to investigate myocardial contrast perfusion imaging using TEE in the operating theater.     

A Harmonic Dual-Frequency Transducer for Acoustic Cluster Therapy

Acoustic Cluster Therapy (ACT) is a two-component formulation of commercially available microbubbles (Sonazoid; GE Healthcare, Oslo, Norway) and microdroplets (perfluorated oil) currently under development for cancer treatment. The microbubbles and microdroplets have opposite surface charges to form microbubble/microdroplet clusters, which are administered to patients together with a drug. When the clusters and drug reach the target tumour, two ultrasound (US) exposure regimes are used: First, high-frequency (>2.0 MHz) US evaporates the oil and forms ACT bubbles that lodge at the microvascular level. Second, low-frequency (0.5 MHz) US induces stable mechanical oscillations of the ACT bubbles, causing localized micro-streaming, radiation and shear forces that increase the uptake of the drugs to the target tumour. This report describes the design and testing of a dual-frequency transducer and a laboratory setup for pre-clinical in vivo studies of ACT on murine tumour models. The dual-frequency transducer utilizes the 5th harmonic (2.7 MHz) and fundamental (0.5 MHz) of a single piezoceramic disk for the high-frequency and low-frequency regimes, respectively. Two different aperture radii are used to align the high-frequency and low-frequency beam maxima, and the high-frequency –3 dB beam width diameter is 6 mm, corresponding to the largest tumour sizes we expect to treat. The low-frequency –3 dB beam width extends 6 mm. Although unconventional, the 5th harmonic exhibit a 44% efficiency and can therefore be used for transmission of acoustic energy. Moreover, both in vitro and in vivo measurements demonstrate that the 5th harmonic can be used to evaporate the microbubble/microdroplet clusters. For the in vivo measurements, we used the kidneys of non-tumour–bearing mice as tumour surrogates. Based on this, the transducer is deemed suited for pre-clinical in vivo studies of ACT and replaces a cumbersome test setup consisting of two transducers.     

组织谐波成像在胆囊病变超声诊断中的应用

目的通过常规基波成像（FI）和组织谐波显像（THI）技术对比,探讨超声自然组织谐波成像在胆囊病变中的应用价值。方法采用基波显像和组织谐波成像对63例胆囊病变患者进行对比观察。结果63例患者FI与THI图像对比分析,后者图像整体质量均得到明显改善。结论组织谐波成像能明显改善二维图像质量,有助于提高超声对胆囊病变的诊断准确率。     

Feasibility and accuracy of left ventricular volumes and ejection fraction determination by fundamental, tissue harmonic, and intravenous contrast imaging in difficult-to-image patients.

The need to enhance the echocardiographic determination of left ventricular ejection fraction is greatest in patients with suboptimal images. Intravenous contrast (CON) and tissue harmonic imaging (THI) are 2 important methods for enhancing endocardial border definition. However, the comparative feasibility and accuracy of THI and contrast-enhanced power harmonic imaging in difficult-to-image patients have not been examined. We assessed the comparative accuracy of THI and CON in determining EF and ventricular volumes in patients with suboptimal fundamental images. We demonstrated that CON is feasible and exhibits a greater correlation with ejection fraction and ventricular volumes determined by radionuclide angiography (standard of comparison) than THI in this difficult-to-image population, with no reported side effects. For both ejection fraction and ventricular volumes, the observer variability was least for CON, intermediate with THI, and greatest for fundamental imaging.     

Comparing differential tissue harmonic imaging with tissue harmonic and fundamental gray scale imaging of the liver.

OBJECTIVE: The purpose of this study was to compare fundamental gray scale sonography, tissue harmonic imaging (THI), and differential tissue harmonic imaging (DTHI) for depicting normal and abnormal livers. METHODS: The in vitro lateral resolution of DTHI, THI, and sonography was assessed in a phantom. Sagittal and transverse images of right and left hepatic lobes of 5 volunteers and 20 patients and images of 27 liver lesions were also acquired. Three independent blinded readers scored all randomized images for noise, detail resolution, image quality, and margin (for lesions) on a 7-point scale. Next, images from the same location obtained with all 3 modes were compared blindly side by side and rated by all readers. Contrast-to-noise ratios were calculated for the lesions, and the depth of penetration (centimeters) was determined for all images. RESULTS: In vitro, the lateral resolution of DTHI was significantly better than fundamental sonography (P = .009) and showed a trend toward significance versus THI (P = .06). In the far field, DTHI performed better than both modes (P < .04). In vivo, 450 images were scored, and for all parameters, DTHI and THI did better than sonography (P < .002). Differential tissue harmonic imaging scored significantly higher than THI with regard to detail resolution and image quality (P < .001). The average increase in penetration with THI and DTHI was around 0.6 cm relative to sonography (P < .0001). The contrast-to-noise ratio for DTHI showed a trend toward significance versus THI (P = .06). Side-by-side comparisons rated DTHI better than THI and sonography in 54% of the cases (P < .007). CONCLUSIONS: Tissue harmonic imaging and DTHI do better than fundamental sonography for hepatic imaging, with DTHI being rated the best of the 3 techniques.     

A new ultrasound instrument for in vivo microimaging of mice

We report here on the design and evaluation of the first high-frequency ultrasound (US) imaging system specifically designed for microimaging of the mouse. High-frequency US or US biomicroscopy (UBM) has the advantage of low cost, rapid imaging speed, portability and high resolution. In combination with the ability to provide functional information on blood flow, UBM provides a powerful method for the investigation of development and disease models. The new UBM imaging system is demonstrated for mouse development from day 5.5 of embryogenesis through to the adult mouse. At a frequency of 40 MHz, the resolution voxel of the new mouse scanner measures 57 microm x 57 microm x 40 microm. Duplex Doppler provides blood velocity sensitivity to the mm per s range, consistent with flow in the microcirculation, and can readily detect blood flow in the embryonic mouse heart, aorta, liver and placenta. Noninvasive UBM assessment of development shows striking similarity to invasive atlases of mouse anatomy. The most detailed noninvasive in vivo images of mouse embryonic development achieved using any imaging method are presented.     

组织谐波显像诊断肝脏病变的临床应用

目的：探讨组织谐波显像对肝脏病变的诊断价值。方法：对比分析56个肝脏病灶的基波显像和组织谐波显像结果。结果：组织谐波显像对病灶的边界和内部回声等状况的显示均明显优于基波显像,对囊性病变尤其明显。结论：组织谐波显像能明显改善图像质量,提高诊断准确性。     

组织谐波成像在腹部脏器的临床应用

目的 探讨组织谐波成像技术在腹部脏器的临床应用价值。方法 分别采用常规基波成像(FI)，及组织谐波成像(THI)对138例腹部脏器正常组及疾病组二维声像图及诊断检出率进行比较。结果 THI明显改善了FI状态下二维图像质量：正常腹部脏器结构及层次显示清晰，疾病组声像图特征明显，提高了检出率及鉴别诊断水平；同时，THI明显减少伪像，增加细微组织结构分辨能力，在胆囊疾病诊断中尤其有意义。结论 随着技术的不断改善，THI能为超声提供更有诊断价值的信息。     

Ultrasonography of the pancreas. 2. Harmonic imaging

Tissue harmonic imaging (THI) is a relatively new ultrasonographic imaging modality which has been implemented in many modern scanners. As several previous studies have pointed out, THI can help to overcome some shortcomings of conventional B-mode ultrasonography (US). The aim of this article is to give a compact summary of the potentials of THI, focused on pancreatic imaging. Beginning with a recapitulation of the technical background of THI, the particularities and suitable applications of THI in US of the pancreas are discussed. Examination protocols and typical indications are presented together with example images. Finally, new trends and developments in B-mode sonography of the pancreas such as panorama US, compound imaging, and photopic US are mentioned     

Evaluation of tissue harmonic imaging for the diagnosis of focal liver lesions

This was a prospective study to evaluate tissue harmonic imaging (THI) for the diagnosis of focal liver lesions. A total of 15 reviewers read 100 randomly arranged liver images, a fundamental grey-scale image (FGI) and a THI (transmitted: 2 MHz, received: 4 MHz) of each of 50 patients (29 with liver cirrhosis, 42 with focal lesions) taken from the same section. The mean value of overall accuracy for detecting lesions (presence or absence) was significantly higher with THI (82.3%) than with FGI (79.6%) (t = 1. 96, p< 0.05). When only the 29 cirrhosis patients were analyzed, the difference was more significant (t = 2.48, p < 0.02). The correct count rate of the number of focal lesions was higher with THI (78. 0%) than with FGI (67.0%) (t = 3.61, p< 0.005) in 23 cirrhosis patients with focal lesions. The correct diagnosis of HCC was achieved at a higher rate with THI (42.5%) than with FGI (36.8%). THI was statistically effective for detecting focal lesions, particularly in cirrhotic livers.     

组织谐波显像诊断胰腺癌的临床应用

目的通过常规基波显像(FI)与组织谐波显像(THI)的对比观察,探讨组织谐波显像诊断胰腺癌的临床应用价值。方法对45例胰腺癌患者(肿块直径小于4cm,无远处转移)进行FI和THI检查,对2种方法所得图像质量进行对比,分析2种检查方法的诊断价值。结果在观察胰腺病灶的大小、边界、内部回声特点、胰管回声及肿块与周围血管的关系等方面,组织谐波显像明显优于基波显像。结论本研究表明,THI可提高胰腺肿块的图像质量,提高病变显示的清晰度及信息量,从而提高诊断准确率。     

Tissue harmonic imaging, frequency compound imaging, and conventional imaging: use and benefit in breast sonography.

OBJECTIVE: The purpose of this study was to evaluate different sonographic settings (tissue harmonic, frequency compounding, and conventional imaging) and to determine which setting optimizes breast lesion detection and lesion characterization. METHODS: Four hundred thirteen consecutive breast lesions (249 benign and 164 malignant) were evaluated by sonography using 4 different modes (conventional imaging at 14 MHz, tissue harmonic imaging at 14 MHz [THI], and frequency compound imaging at 10 MHz [CI10] and 14 MHz [CI14]). The images were reviewed by consensus by 2 breast radiologists. For each image, the lesion was graded for conspicuity, mass margin assessment, echo texture assessment, overall image quality, and posterior acoustic features. RESULTS: For lesion conspicuity, THI and CI14 were better than conventional imaging (P < .01) and CI10 (P < .01) particularly against a fatty background (P < .01 for THI versus conventional for a fatty background versus P = .13 for a dense background). Frequency compound imaging at 10 MHz performed the best in echo texture assessment (P < .01), as well as overall image quality (P < .01). For margin assessment, CI10 performed better for deep and large (> or =1.5-cm) lesions, whereas CI14 performed better for small (<1.5-cm) and superficial lesions. Finally, THI and CI14 increased posterior shadowing (P < .01) and posterior enhancement (P < .01). CONCLUSIONS: The standard breast examination incorporates 2 distinct processes, lesion detection and lesion characterization. With respect to detection, THI is useful, especially in fatty breasts. With respect to characterization, compound imaging improves lesion echo texture assessment. No single setting in isolation can provide the necessary optimized information for both of these tasks. As such, a combination approach is best.     

组织谐波显像技术在肝胆系统疾病临床诊断中的应用

目的:探讨组织谐波显像技术(THI)在肝胆系统疾病临床诊断中的应用。方法:选择2003年—2007年常规超声检查图像不理想的78例患者,对其常规基波显像(FI)检查及THI检查结果进行比较分析。结果:肝病组及胆系疾病组在二维超声FI基础上,加入THI后,能很明显地提高灰阶对比度,脏器的内部结构及边缘回声显示有明显的改善,脏器内实性肿块的轮廓清晰度有明显改善。结论:THI可明显提高FI的图像质量,提高二维检出率,具有较高的临床诊断价值。     

Contribution of tissue harmonic imaging and frequency compound imaging in interventional breast sonography.

OBJECTIVE: The purpose of this study was to retrospectively compare conventional imaging, frequency compound imaging (CI), and tissue harmonic imaging (THI) in interventional breast sonography. METHODS: Institutional Review Board approval and patient informed consent were not required. The authors reviewed 104 sonographically guided breast procedures in 83 patients. For each biopsy, 4 images obtained with conventional imaging, frequency CI at 10 and 14 MHz (CI10 and CI14), and THI were graded independently by 2 radiologists for lesion conspicuity, needle conspicuity, lesion and needle conspicuity, and overall image quality. Frequency CI at 10 MHz, CI14, and THI were compared with conventional imaging. Different clinical scenarios (fatty versus glandular background, fine needle versus core needle, and oblique versus horizontal needle direction) were evaluated. RESULTS: Statistical analysis showed that for overall image quality, CI10 was the best setting (odds ratios [OR], 3.67 and 7.48). For lesion conspicuity, CI14 (OR, 3.55) and THI (OR, 1.77) improved lesion visibility in a fatty background, whereas THI (OR, 0.26) was very limited in a glandular background. For needle conspicuity, no setting was better than conventional, whereas THI was the least valuable setting (OR, 0.011 and 0.049). For lesion and needle conspicuity, CI10 showed significantly better results than conventional for a dense background (P = .0268 and .4028; OR, 2.435 and 1.383) with 1 reviewer, whereas THI was the least valuable setting (OR, 0.014 and 0.042). CONCLUSIONS: Conventional imaging provided the best assessment of lesion and needle conspicuity. Frequency compounding is a useful setting for dense breast and for fine-needle aspiration. Tissue harmonic imaging has a role in the visualization of a lesion against a fatty background but is of limited value in needle visualization.     

Two dimensional arrays for real time 3D intravascular ultrasound

We have previously described 2D arrays operating at up to 10.0 MHz consisting of several thousand elements for transthoracic cardiac imaging and over a hundred elements for intracardiac imaging using 7 Fr to 12 Fr catheters. We have begun to explore forward viewing real time 3D phased array intravascular ultrasound, which may require imaging depths of a few centimeters to look down the axis of a vessel to view vulnerable atherosclerotic plaque. We used a noncoaxial based cable technology that allowed 100 signal wires to be placed inside a4.8 French IVUS lumen with an inner diameter of 1.3 mm. We pursued two different fabrication technologies for the building of the transducers. Each transducer was constructed in the forward viewing configuration to allow simultaneous real time B-scans, C-scans and volumetric rendering of vessels and vascular stents distal to the catheter tip. In order to obtain the desired penetration depth, each transducer was constructed to operate at 10.0 MHz. The first method included an ordered array of 11 x 11 = 121 elements. In order to conform to the round aperture of the IVUS lumen, the comers were cut off, resulting in a total of 97 signal channels. Real time images include a 4 mm diameter vessel in a tissue mimicking phantom, an expanded stent and a stent in an excised sheep aorta. The second method is based upon a laser dicing technique that cuts the individual elements in a random pattern. This resulted in 61 signal channels. Real time 3D images of the AIUM test object were made with this transducer.