Sheng-Min Huang

Instantaneous frequency-based ultrasonic temperature estimation during focused ultrasound thermal therapy.

Focused ultrasound thermal therapy relies on temperature monitoring for treatment guidance and assurance of targeting and dose control. One potential approach is to monitor temperature change through ultrasonic-backscattered signal processing. The current approach involves the detection of echo time-shifts based on cross-correlation processing from segmented radiofrequency (RF) data. In this study, we propose a novel ultrasonic temperature-measurement approach that detects changes in instantaneous frequency along the imaging beam direction. Focused ultrasound was used as the heating source, and the 1-D beamformed RF signals provided from an ultrasound imager were used to verify the proposed algorithm for temperature change estimation. For comparison, a conventional cross-correlation technique was also evaluated. Heating experiments testing tissue-mimicking phantoms and ex vivo porcine muscles were conducted. The results showed that temperature can be well estimated by the proposed algorithm in the temperature range, where the relationship of sound speed versus temperature is linear. Compared with the cross-correlation-based algorithm, the proposed new algorithm yields a six-fold increase in computational efficiency, along with comparable contrast-detection ability and precision. This new algorithm may serve as an alternative method for implementing temperature estimation into a clinical ultrasound imager for thermal therapy guidance.

Paramagnetic perfluorocarbon-filled albumin-(Gd-DTPA) microbubbles for the induction of focused-ultrasound-induced blood–brain barrier opening and concurrent MR and ultrasound imaging

This paper presents new albumin-shelled Gd-DTPA microbubbles (MBs) that can concurrently serve as a dual-modality contrast agent for ultrasound (US) imaging and magnetic resonance (MR) imaging to assist blood-brain barrier (BBB) opening and detect intracerebral hemorrhage (ICH) during focused ultrasound brain drug delivery. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×10(9) MBs ml(-1) using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C(3)F(8)) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd(3+) ions were eliminated (which were detected by the xylenol orange sodium salt solution). The albumin-(Gd-DTPA) MBs were also characterized and evaluated both in vitro and in vivo by US and MR imaging. Focused US was used with the albumin-(Gd-DTPA) MBs to induce disruption of the BBB in 18 rats. BBB disruption was confirmed with contrast-enhanced T(1)-weighted turbo-spin-echo sequence MR imaging. Heavy T(2)*-weighted 3D fast low-angle shot sequence MR imaging was used to detect ICH. In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T(1)-, T(2)- and T(2)*-weighted MR images. The r(1) and r(2) relaxivities for Gd-DTPA were 7.69 and 21.35 s(-1)mM(-1), respectively, indicating that the MBs represent a positive contrast agent in T(1)-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce disruption of the BBB and detect ICH. To compare the signal intensity change between pure BBB opening and BBB opening accompanying ICH, albumin-(Gd-DTPA) MB imaging can provide a ratio of 5.14 with significant difference (p = 0.026), whereas Gd-DTPA imaging only provides a ratio of 2.13 and without significant difference (p = 0.108). The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from ICH, and can monitor the focused ultrasound brain drug delivery process.

Focal beam distortion and treatment planning for transrib focused ultrasound thermal therapy: A feasibility study using a two-dimensional ultrasound phased array

PURPOSE The purpose of this study is to numerically investigate the feasibility of employing a spherical-section ultrasound phased array for transrib thermal ablation of liver tumors. METHODS Based on CT images, the authors performed a 3D reconstruction of the ribs and the surrounding soft tissues. A 3D pseudospectral time-domain (PSTD) solver was used to assess wave propagation and the distribution of pressure, with the aim of determining the specific absorption rate (SAR) and the resulting thermal doses and dynamics. Phase aberrations caused by the interposed ribs were corrected to assess the efficacy of the device in improving the SAR gain between the ribs and the target positions. RESULTS Experimental results supported the usefulness of the PSTD solver for predicting the pressure distribution due to the interfering obstacle. In addition, the method allowed the correction of phase aberrations caused by the ribs, and a significant improvement (176%) in the SAR gain between the ribs and the target points was observed at specific frequencies. CONCLUSIONS The method allowed successful tissue targeting without causing overheating of the ribs. One main advantage of this approach is the accurate estimation of phase aberration caused by heterogeneously porous ribs and other interposed tissues. This strategy might prove useful to assess the effectiveness and safety of focused ultrasound thermal ablation prior to transrib treatment.

Beamforming effects on generalized Nakagami imaging

Ultrasound tissue characterization is crucial for the detection of tissue abnormalities. Since the statistics of the backscattered ultrasound signals strongly depend on density and spatial arrangement of local scatterers, appropriate modeling of the backscattered signals may be capable of providing unique physiological information on local tissue properties. Among various techniques, the Nakagami imaging, realized in a window-based estimation scheme, has a good performance in assessing different scatterer statistics in tissues. However, inconsistent m values have been reported in literature and obtained only from a local tissue region, abating the reliability of Nakagami imaging in tissue characterization. The discrepancies in m values in relevant literature may stem from the nonuniformity of the ultrasound image resolution, which is often neglected. We therefore hypothesized that window-based Nakagami m estimation was highly associated with the regional spatial resolution of ultrasound imaging. To test this hypothesis, our study investigated the effect of beamforming methods, including synthetic aperture (SA), coherent plane wave compounding (CPWC), multi-focusing (MF), and single-focusing (SF), on window-based m parameter estimation from the perspective of the resolution cell. The statistics of m parameter distribution as a function of imaging depth were characterized by their mean, variance, and skewness. The phantom with a low scatterer density (16 scatterers mm(-3)) had significantly lower m values compared to the ones with high scatterer densities (32 and 64 scatterers mm(-3)). Results from the homogeneous phantom with 64 scatterers mm(-3) showed that SA, MF, and CPWC had relatively uniform lateral resolutions compared to SF and thus relatively constant m estimates at different imaging depths. Our findings suggest that an ultrasound imaging regime exhibiting invariant spatial resolution throughout the entire imaging field of view would be the most appropriate for Nakagami imaging for tissue characterization.

Improved temperature imaging of focused ultrasound thermal therapy using a sigmoid model based cross-correlation algorithm

Focused ultrasound (FUS) thermal therapy relies on temperature imaging for treatment monitoring and guidance. Current ultrasonic temperature estimation mainly involves the detection of echo-time shifts using cross-correlation processing between segmented radio-frequency (RF) data pre- and post-FUS heating. Generally, a minimum RF data segment of around 6 wavelengths is required to obtain accurate echo-time shift estimates and mitigate artifacts. Shorter data segments are essential to retrieve better axial resolution in temperature image; however, shorter data segments generally lead to increased estimation errors. In this work, we propose a sigmoid model based cross-correlation algorithm to address this problem. First, cross-correlation processing with a large non-overlapping window (e.g., around 10 wavelengths) is applied to obtain coarse echo-time shift estimates between RF data pre- and post-FUS heating. According to the feature of the echo-time shift from FUS heating, a sigmoid model is adopted to fit the coarse estimates, and used as the initial estimates for the further cross-correlation processing with a smaller window (e.g., 2 wavelengths) which improves axial resolution and suppress artifacts while providing comparable noise properties to those obtained by the conventional method with a 6-wavelength window. The experimental results showed that this new method can provide accurate echo-time shift estimation and mitigate the artifacts while only requiring less than a 2-wavelength data segment. This work helps to improve axial resolution of the current ultrasonic temperature estimation used for guidance of the FUS thermal ablation procedure.

A novel ultrasonic-imaging based temperature estimation approach by instantaneous frequency detection

Focused ultrasound thermal therapy relies on temperature monitoring for treatment guidance and assurance of targeting and dose control; a potential approach to achieve these is ultrasonic temperature estimation. The approach used currently involves the detection of echo time shifts based on cross-correlation processing from the segmented radio-frequency (RF) data. In this study, we propose a novel 2D ultrasonic temperature measurement approach by detecting changes in instantaneous frequency. We proposed a novel echo time-shift based algorithm to perform fast temperature estimation from ultrasonic imaging. This new algorithm may serve as an alternative for implementing 2D temperature estimation into a clinical ultrasound imager. Focused ultrasound was used as the heating source, and the beamformed RF signals provided from a 2D ultrasound imager were used to verify the proposed algorithm for temperature change estimation. For comparison, a conventional cross-correlation technique was also evaluated. Heating experiments of tissue-mimicking phantoms and ex-vivo porcine muscles were conducted. Our results show that the proposed new algorithm yields up to six times better computational efficiency while its contrast detection ability and precision rival those of cross-correlation-based algorithm. In the ex-vivo tissue experiments, we also presented the irreversibility of the echo time-shift effect in the necrotic region, which is different from that in the tissue-mimicking phantoms. In this study, we propose a new approach for temperature estimation by employing instantaneous frequency detection; it was implemented by using a simple zero-crossing algorithm. Some of the features of this approach are its superior computational efficiency and the possibility of higher spatial resolution for temperature mapping. Further, the experimental results have demonstrated that the proposed algorithm can provide similar temperature detection ability and precision as compared to the cross-correlation algorithm. Tissue irreversibility when approaching the necrotic temperature encounters difficulty in accurate temperature estimation, which has been proposed and discussed as an alternative possibility to detect tissue necrosis rather than temperature. This provides useful information as well as an alternative for the clinical applications of such an ultrasound-based temperature estimation technology.

High frame rate ultrasound monitoring of high intensity focused ultrasound-induced temperature changes: A novel asynchronous approach

PURPOSE When applying diagnostic ultrasound to guide focused ultrasound (FUS) thermal therapy, high frame rate ultrasonic temperature monitoring is valuable in better treatment control and dose monitoring. However, one of the potential problems encountered when performing ultrasonic temperature monitoring of a FUS procedure is interference between the FUS and imaging systems. Potential means of overcoming this problem include the switch between the FUS system and the imaging system (limited by a reduced frame rate of thermal imaging) or the development of complex synchronization protocols between the FUS therapeutic system and the ultrasonic imaging apparatus (limited by implementation efforts both for software and hardware designs, and low potential for widespread diffusion). In this paper, we apply an asynchronous idea to retrieving high frame rate and FUS-interference-free thermal imaging during FUS thermal therapy. METHODS Tone-burst delivery mode of the FUS energy is employed in our method, and the imaging and FUS systems are purposely operated in an asynchronous manner. Such asynchronous operation causes FUS interference to saturate sequential image frames at different A-lines; thus clean A-lines from several image frames can be extracted by a total energy-thresholding technique and then combined to reconstruct interference-free B-mode images at a high frame rate for temperature estimation. The performance of the proposed method is demonstrated by phantom experiments. Relationships of the FUS duty-cycle with the maximum reconstructed frame rate of thermal imaging and the corresponding maximum temperature increase are also studied. Its performance was also evaluated and compared with the existing manually synchronous and synchronous approaches. RESULTS By proper selection of the FUS duty-cycle, using our method, the frame rate of thermal imaging can be increased up to tenfold compared with that provided by the manually synchronous approach. Our method is capable of pushing the frame rate of thermal images to the same order as that of the synchronous approach while avoiding sacrificing the observable field of view (FOV) of temperature mapping. CONCLUSIONS The asynchronous method can be easily implemented and allows thermal imaging at an improved frame rate, without the need for complex synchronization protocols between the FUS therapeutic system and the ultrasonic imaging apparatus and without sacrifice of observable FOV. This technology may provide an effective alternative for real-time temperature measuring during thermal ablation procedures and can be easily integrated into current high intensity focused ultrasound systems.

Ultrasonic Nakagami Imaging of High-intensity Focused Ultrasound-induced Thermal Lesions in Porcine Livers: Ex Vivo Study

High-intensity focused ultrasound (HIFU) has demonstrated the capacity to be used for local thermal ablation in clinical surgery; however, relying solely on conventional ultrasound B-mode imaging to monitor HIFU thermal ablation and determine ablation levels remains a challenge. Here, we experimentally demonstrate the ability to use Nakagami imaging to monitor HIFU-induced thermal lesions in porcine livers ex vivo. Ultrasonic Nakagami imaging has been proven to be able to characterize tissues with different scatterer concentrations and distributions. The pathological sections from HIFU thermally ablated porcine liver tissues reveal that normal and denatured tissues significantly differ in scatterer concentration and distribution. Therefore, we believe that Nakagami imaging can be used to monitor thermal ablation by tracing Nakagami parameter changes in liver tissues. The ex vivo porcine liver experiments were performed using a homemade HIFU device synchronized with a commercial diagnostic ultrasound scanner to obtain the ultrasound envelope data before and after thermal ablation. These data were used to evaluate the performance of thermal lesion characterization using Nakagami imaging and were compared with those derived from conventional B-mode imaging. Experimental results showed that Nakagami imaging can be used to identify thermal lesions, which are difficult to visualize using conventional B-mode imaging because there is no apparent bubble formation. In cases with apparent bubble formation, Nakagami imaging could provide a more accurate estimation of lesion size and position. In addition, the Nakagami imaging algorithm is characterized by low computational complexity, which means it can be easily integrated as postprocessing for existing array imaging systems.

A unified approach for ultrasound-monitored focused ultrasound thermal therapy: Combination of temperature estimation and Nakagami—Based necrosis-formation detection

It has been well recognized that echo-time shift of the ultrasound radio-frequency (RF) signals can reflect temperature change during focused ultrasound (FUS) thermal ablation, and thus has potential for treatment monitoring and guidance. Nevertheless, temperature estimates based on this approach become uncertain when temperature rises to tissue necrotic level (>; 50°C). To address this, we propose a unified approach that exploits the merits of ultrasonic temperature estimation and Nakagami imaging to provide a total solution for monitoring of FUS thermal therapy. Our previous studies demonstrate the potential of Nakagami visualization of FUS-induced thermal lesions. Here ultrasonic temperature estimation is used to locate treatment region before tissue coagulation occurs while Nakagami imaging is applied to track the thermal lesion formation. In this study, we experimentally demonstrated that ultrasonic temperature estimation and tissue necrosis detection by Nakagami imaging can serve as complementary roles; thus their integration can provide a total solution that fulfills the monitoring of the overall heating process. This work may help to improve the current clinical practice, which uses ultrasound to guide the FUS thermal ablation procedure.

US/MRI dual modality contrast agent for concurrent MR and ultrasonic imaging of focused-ultrasound induced blood-brian barrier opening

Targeted drug delivery by magnetic resonance (MR)-guided ultrasound (US)-induced blood-brain barrier (BBB) disruption has been developed using focused US in combination with encapsulated gas-filled microbubbles (MBs). However, the occurrence of intracerebral hemorrhage may hamper the usefulness of US-induced BBB opening, which is effectively indicated by gadolinium (Gd)-based contrast enhancement in T1-weighted MR scans. This paper reports the dual function of paramagnetic particles of perfluorocarbon-filled albumin-gadolinium-diethylene-triamine penta-acetic acid (Gd-DTPA) MBs for BBB opening and for distinguishing between focused-US-induced BBB opening and intracerebral hemorrhage in MR contrast images. Perfluorocarbon-filled albumin-(Gd-DTPA) MBs were prepared with a mean diameter of 2320 nm and concentration of 2.903×109 MBs/ml using albumin-(Gd-DTPA) and by sonication with perfluorocarbon (C3F8) gas. The albumin-(Gd-DTPA) MBs were then centrifuged and the procedure was repeated until the free Gd3+ ions were eliminated (which were detected by xylenol orange sodium salt solution). In vitro US imaging experiments showed that albumin-(Gd-DTPA) MBs can significantly enhance the US contrast in T1-, T2-, and T2∗-weighted MR images. The r1 and r2 relaxivities for Gd-DTPA were 7.69 and 21.35 s−1 mM−1, respectively, indicating that the MBs represent a positive contrast agent in T1-weighted images. In vivo MR imaging experiments on 18 rats showed that focused US combined with albumin-(Gd-DTPA) MBs can be used to both induce and detect disruption of the BBB. After disrupting the BBB, the leakage of albumin-(Gd-DTPA) MBs shells can be detected for distinguishing between focused-US-induced disruption of the BBB and intracerebral hemorrhage in T1-weighted images. The results indicate that albumin-(Gd-DTPA) MBs have potential as a US/MR dual-modality contrast agent for BBB opening and differentiating focused-US-induced BBB opening from intracerebral hemorrhage.