Skin-scanning technique for superficial blood flow imaging using a high-frequency ultrasound system.

In this paper we propose a skin-scanning technique with a high-frequency ultrasound imaging system that enables images to be acquired at the fixed depth of field of a single-element focused transducer along the profile of an object contour by simultaneously moving the transducer in the horizontal and vertical directions. The scanning path, which closely parallels the profile of the object contour, was determined from the intensity difference between an object and the background in a brightness-mode image. The transducer moved along the profile of the object contour while maintaining a constant distance interval between adjacent pairs of ultrasonic signals in the horizontal direction. The image was then reconstructed by applying an alignment process to eliminate the distortion. The performance of skin-scanning technique was verified in vitro experiment using an arc-shaped phantom and the results showed a percentage error of 0.55% for the volumetric blood flow estimates. Moreover, in vivo experiment on a subcutaneous tumor was also performed. The results indicated that the proposed technique can accurately estimate the blood flow information along the profile of the object contour and avoid distortion of the morphology of blood vessels. The skin-scanning technique has potential for assessing superficial blood flows and prognoses in the oncology and dermatology fields.

A preclinical study to explore vasculature differences between primary and recurrent tumors using ultrasound Doppler imaging.

The purpose of this preclinical study was to perform a longitudinal investigation of the function and morphology of the vasculatures of primary and recurrent tumors, because recurrent tumors have lower curability. Thus, elucidating differences in the features of the vasculatures of primary and recurrent tumors could help to improve tumor therapies. The transgenic adenocarcinoma of the mouse prostate tumors were transplanted in nonirradiated and with 25 Gy of preirradiation normal tissues to produce the primary and recurrent tumor models, respectively. The perfusion and branching index of tumor vasculatures were characterized to reveal the function and morphology information, respectively. The blood vessels were more dilated and continuous in recurrent tumors than in primary tumors. During tumor progression, the perfusion increased in primary tumors but did not change significantly in recurrent tumors. The tumor perfusion was lower in recurrent tumors than in primary tumors, whereas branching index in 2-D ultrasound images did not differ between the two tumor models. Furthermore, the introducing 3-D volumetric power Doppler image may have the potential for accurately revealing the morphologic features within tumors. The results of this study suggest that power Doppler imaging is an easily applied and rapid method for noninvasively assessing the vascular features of primary and recurrent tumors and for exploring differences between their vasculature pathways.

Characterization of tumor vasculature distributions in central and peripheral regions based on Doppler ultrasound.

PURPOSE: Tumor heterogeneity is a major obstacle to therapy, and thus, how to achieve the maximal therapeutic gain in tumor suppression is an important issue. To accomplish this goal, assessing changes in tumor behaviors before treatment is helpful for physicians to adjust treatment schedules. In this study, the authors longitudinally and spatially investigated tumor perfusion and vascular density by power Doppler imaging and immunohistochemical analysis, respectively. Moreover, the authors developed a method to describe quantitatively the spatial distribution of the vasculature within the central and peripheral regions of tumors. METHODS: Tumor perfusion was estimated by power Doppler images at an operating frequency of 25 MHz. To avoid the attenuation effect of such high-frequency ultrasound, murine tumors were subcutaneously transplanted into the thighs of mice and then monitored for 11 days. The tumors were removed at various time intervals for immunohistochemical analysis of their vascular density using CD31 staining. The spatial characteristics of the tumor vasculature were quantified by a γ value, which characterizes the rate at which vascular signals increase with the fractional sizes of the peripheral area within the tumor. RESULTS: During tumor progression, the volume of tumor perfusion in the power Doppler images was strongly correlated with the vascular density determined by immunohistochemical analysis. In addition, the γ value significantly decreased with increased tumor size in the power Doppler images but not in the immunohistochemical analysis. CONCLUSIONS: Although the tumor perfusion and vascular density estimates showed good temporal correlations during tumor progression, they did not show good spatial correlations due to tumor perfusion patterns changing from homogeneous to heterogeneous. In contrast to the perfusion patterns, the vascular density of the tumor remained uniformly distributed. In the present study, no necrosis regions were found in the tumor experiments. Furthermore, the measurement of γ value is a simple method for assessing the vasculatures of spatial distribution within tumors.

Assessment of tumor vasculature for diagnostic and therapeutic applications in a mouse model in vivo using 25-MHz power Doppler imaging.

OBJECTIVE: The blood flow rate in the microcirculation associated with angiogenesis plays an important role in the progression and treatment of cancer. Since the microvascular status of tumor vessels can yield useful clinical information, assessing changes in the tumor microcirculation could be particularly helpful for tumor evaluation and treatment planning. METHODS: In this study we used a self-developed 25-MHz ultrasound imaging system with a spatial resolution of 150 µm for assessing tumor-microcirculation development and the pattern of the vasculature in three tumor-bearing mice in vivo based on power Doppler images. The total Doppler power (DP) and color pixel density (CPD) revealed the presence of functional vessels distributed throughout a tumor volume. The vasculature distributions in the core and periphery were compared to the regulation of vasculature function, which facilitated determination of when the tumor grew rapidly. RESULTS: The data obtained from a quantified analysis of power Doppler images indicated that the tumor vascularity initially increased throughout the tumor. Both DP and CPD increased rapidly in the tumor periphery when the tumor volume exceeded 10mm(3). CONCLUSION: Our preclinical findings suggest that power Doppler imaging could be useful for detecting the changes in tumor vascular perfusion and for determining the optimal treatment timing when a tumor begins its rapid volumetric growth.

In vivo imaging of blood flow in the mouse Achilles tendon using high-frequency ultrasound.

OBJECTIVE: Achilles tendinitis is a common clinical problem with many treatment modalities, including physical therapy, exercise and therapeutic ultrasound. However, evaluating the effects of current therapeutic modalities and studying the therapeutic mechanism(s) in vivo remains problematic. In this study, we attempted to observe the morphology and microcirculation changes in mouse Achilles tendons between pre- and post-treatment using high-frequency (25 MHz) ultrasound imaging. A secondary aim was to assess the potential of high-frequency ultrasound in exploring therapeutic mechanisms in small-animal models in vivo. METHODS: A collagenase-induced mouse model of Achilles tendinitis was adopted, and 5 min treatment of continuous-mode low-frequency (45 kHz) ultrasound with 47 mW/cm(2) maximum intensity and 16.3 cm(2) effective beam radiating area was applied. The B-mode images showed no focal hypoechoic regions in normal Achilles tendons either pre- or post-treatment. The Doppler power energy and blood flow rate were measured within the peritendinous space of the Achilles tendon. CONCLUSION: An increase in the microcirculation was observed soon after the low-frequency ultrasound treatment, which was due to immediate induction of vascular dilatation. The results suggest that applying high-frequency Doppler imaging to small-animal models will be an invaluable aid in explorations of the therapeutic mechanism(s). Our future work includes using imaging to assess microcirculation changes in tendinitis between before and after treatment over a long time period, which is expected to yield useful physiological data for future human studies.