Water Specific MRI T1 Mapping for Evaluating Liver Inflammation Activity Grades in Rats With Methionine-Choline-Deficient Diet-Induced Nonalcoholic Fatty Liver Disease.

BACKGROUND: Early detection and grading of liver inflammation are important for the management of nonalcoholic fatty liver disease (NAFLD) patients. There is still lack of a noninvasive way for the inflammation characterization in NAFLD. PURPOSE: To assess liver inflammation grades by water specific T1 (wT1) in a rat model. STUDY TYPE: Prospective. ANIMAL MODEL: A total of 65 male rats with methionine-choline-deficient diet-induced NAFLD and 15 male normal rats as control. FIELD STRENGTH/SEQUENCE: A 3 T; multiecho variable flip angle gradient echo sequence. ASSESSMENT: The wT1 and proton density fat fraction were quantified. Inflammation and fibrosis were assessed histologically with H&E and Sirius red stained slices according to the nonalcoholic steatohepatitis scoring system. Inflammation grade was scored with G0/G1/G2/G3 as none/mild/moderate/severe inflammation in NALFD rats. G0 + G1 and G2 + G3 were combined as none-to-mild grade (GL) and moderate-to-severe grade (GH) inflammation groups. STATISTICAL TESTS: Analysis of variance (ANOVA), Mann-Whitney U test, Spearman's correlation, and receiver operating characteristic (ROC) analysis were performed. The areas under ROC (AUROC) was used for the diagnostic performance of wT1 in discriminating GH and GL. A P value < 0.01 was considered statistically significant. RESULTS: Seventy-six rats were included in the analysis. The numbers in G0-G3 groups were 5, 16, 13, and 27. wT1 of G0-G3 was 568.55 ± 63.93 msec, 582.53 ± 62.98 msec, 521.21 ± 67.31 msec, and 508.79 ± 60.53 msec. A moderate but significant negative correlation between wT1 and histopathological inflammation grades was observed (rs  = -0.42). The wT1 of GH (512.80 ± 62.22 msec) was significantly lower than GL (579.20 ± 61.89 msec). The AUROC of wT1 was 0.79, and the optimal cut-off of wT1 was 562.64 msec (sensitivity: 90%, specificity: 76%), for the discrimination of GL and GH. DATA CONCLUSIONS: wT1 could differentiate none-to-mild inflammation from moderate-to-severe inflammation in the early stage of the NAFLD rat model. EVIDENCE LEVEL: 1 TECHNICAL EFFICACY: Stage 1.

MARFit: An Integrated Software for Real-Time MR Guided Focused Ultrasound Neuromodulation System.

MR guided focused ultrasound (MRgFUS) therapy has been a promising treatment modality for many neurological disorders. However, the lack of real-time image processing software platform sets barriers for relevant pre-clinical researches. This work intends to develop an integrated software for MRgFUS therapy. The software contains three functional modules: a communication module, an image post-processing module, and a visualization module. The communication module provides a data interface with an open-source MR image reconstruction platform (Gadgetron) to receive the reconstructed MR images in real-time. The post-processing module contains the algorithms of image coordinate registration, focus localization by MR acoustic radiation force imaging (MR-ARFI), temperature and thermal dose calculations, motion correction, and temperature feedback control. The visualization module displays monitoring information and provides a user-machine interface. The software was tested to be compatible with systems from two different vendors and validated in multiple scenarios for MRgFUS. The software was tested in many ex vivo and in vivo experiments to validate its functions. The in vivo transcranial focus localization experiments were carried out for targeting the focused ultrasound in neuromodulation.

Feasibility of ultrasound-induced blood-brain barrier disruption with a single-element transducer under three different frequencies in two non-human primates in vivo: Case report.

BACKGROUND: Single-element focused transducers applied in blood-brain barrier (BBB) disruption experiments to optimize intravascular therapies in CNS diseases have the advantage of low cost and portability. Most of the in vivo studies on non-human primates report the use of single-element transducers with an annular spherical shape and a central frequency of 500 kHz. High-frequency ultrasound has smaller focal area and less standing-wave effect but lower transcranial penetration efficiency. Our study reports the feasibility and safety concerns of BBB opening by single-element spherical transducers with central frequencies of 300, 650 and 800 kHz on two rhesus macaques. METHODS: Pulsed ultrasound exposure (3-minute duration, 0.5-1% duty cycle) combined with microbubble injection (SonoVue, 0.2uL/g) was used to disrupt the BBB of the monkeys under the magnetic resonance imaging (MRI) guidance. Gadolinium contrast-enhanced MRI was used to confirm and evaluate the BBB opening after sonication. T2-weighted fast spin echo and T2 * -weighted gradient echo sequences were used to check the post-sonication complications, such as edema and micro-bleeding. RESULTS: Contrast enhancement was found on the post-sonication T1 weighted images for all experiments, showing that the BBB was successfully opened under all the three frequencies on both monkeys. The enhanced area was largest at the lowest frequency. No obvious hypo-intensity or hyper-intensity was observed on either the T2 * weighted gradient echo images or T2-weighted fast-spin echo images, implying the safety of the opening procedure. However, signal enhancement was also observed in the subarachnoid space of the sulci for all frequencies, indicating that the BBB was also disrupted in the propagation path outside the focal area. CONCLUSIONS: The feasibility of BBB opening with single-element transducer under frequencies ranging from 300 kHz to 800 kHz was confirmed by experiments in two non-human primates in vivo. Further investigation into the off-target effects and transducer configurations is needed for safety optimization.

Highly accelerated magnetic resonance acoustic radiation force imaging for in vivo transcranial ultrasound focus localization: A comparison of three reconstruction methods.

Magnetic resonance acoustic radiation force imaging (MR-ARFI) is a promising tool for transcranial neurosurgery planning and monitoring. However, the ultrasound dose during ARFI is quite high due to the high intensity required and the repetitive ultrasound sonication. To reduce the ultrasound deposition and prevent unwanted neurological effects, undersampling in k-space data acquisition is adopted in the current study. Three reconstruction methods, keyhole, k-space hybrid and temporal differences (TED) compressed sensing, the latter two of which were initially proposed for MR thermometry, were applied to the in vivo transcranial focus localization based on MR-ARFI data in a retrospective way. The accuracies of the three methods were compared with the results from the fully sampled data as reference. The results showed that the keyhole method tended to smooth the displacement map and underestimate the peak displacement. The K-space hybrid method was better at recovering the displacement map and was robust to the undersampling pattern, while the TED method was more time efficient under a higher image resolution. For an image of a lower resolution, the K-space hybrid and TED methods were comparable in terms of accuracy when a high undersampling rate was applied. The results reported here facilitate the choice of appropriate undersampled reconstruction methods in transcranial focal localization based on MR-ARFI.

MR-guided blood-brain barrier opening induced by rapid short-pulse ultrasound in non-human primates.

BACKGROUND: Opening the blood-brain barrier (BBB) with focused ultrasound and microbubbles (MBs) has potential use in non-invasive targeted therapy for central nervous system (CNS) diseases. Rapid short-pulse (RaSP) ultrasound with a microsecond sequence has been proposed as a minimally disruptive and efficient method for opening the BBB. This work aimed to test the feasibility and safety of BBB opening in a non-human primate model using combined RaSP ultrasound sequence and MBs. METHODS: The BBB of 2 rhesus macaques were opened with RaSP and the commonly used 10 millisecond long pulse (LP), combined with microbubble (SonoVueTM, 0.2 µL/g) injection in a bolus. The transducer's central frequency was 300 kHz, and the acoustic pressure was set to 0.56 MPa calibrated in water. The BBB opening procedure was guided and evaluated with contrast-enhanced magnetic resonance imaging. The relative signal enhancement was compared between RaSP and LP sonication. T2-weighted fast-spin echo (FSE) and T2*-weighted gradient echo (GRE) sequences were scanned to evaluate edema and micro-bleeding at the end of the procedure. RESULTS: The relative signal enhancement was significantly higher (P<0.01) in the focal area compared to a similar area of the opposite hemisphere at all time points after sonication in each monkey, indicating the successful opening of the BBB. The relative signal enhancement in RaSP reached more than 60% of that with LP in our experiment, while the energy deposition was only 6% of LP. No edema or hemorrhage was found on magnetic resonance images after RaSP. CONCLUSIONS: Combined RaSP ultrasound and MBs for the BBB opening is a practical method in large animal models.

Simultaneous acoustic radiation force imaging and MR thermometry based on a coherent echo-shifted sequence.

BACKGROUND: Simultaneous magnetic resonance (MR) acoustic radiation force imaging (ARFI) and MR thermometry (MRT) (STARFI) based on coherent echo-shifted (cES) sequence was proposed and comprehensively compared to radiofrequency (RF)-spoiled gradient echo (spGRE) STARFI. METHODS: Through use of delicately designed gradients, a collection of echoes was delayed by one repetition time (TR) cycle. The crusher gradient after readout (RO) was used as the displacement encoding gradient (DEG). The sequence was intrinsically sensitive to temperature. High-intensity focused ultrasound (HIFU) pulses were interleaved ON/OFF in successive TRs to separate the phase changes induced by displacement due to acoustic radiation force (ARF) impulses and temperature. Bloch simulation was performed to study the phase sensitivity to displacement of the proposed cES STARFI and spGRE STARFI. The proposed cES sequence was evaluated and compared to spGRE STARFI in ex vivo porcine muscle and ex vivo porcine brain. RESULTS: The minimally achievable TR of cES STARFI was shorter than that of spGRE STARFI, indicating that the cES sequence was more time efficient. It was verified through Bloch simulation and ex vivo experiments that the phase sensitivity to displacement of cES STARFI was higher than that of spGRE STARFI. The optimal trigger delays of cES STARFI and spGRE STARFI in ex vivo porcine muscle were toffset =-2 and -1 ms, respectively. The displacement-induced phase change to acoustic pressure slopes of cES STARFI were 0.079, 0.079, and 0.047 rad/Mpa across the three muscle samples, while the slopes of spGRE STARFI were only 0.047, 0.052, and 0.027 rad/Mpa. The maximum temperature difference between cES STARFI and spGRE STARFI was 1.1 °C. In ex vivo porcine brain, both the displacement-induced phase-to-noise ratio (PNRd) and the temperature uncertainty of cES STARFI were better than those of spGRE STARFI (P<0.05). The temperature and displacement-induced phase change maps of cES STARFI and spGRE STARFI during HIFU treatment were in good accordance in time and spatial location. CONCLUSIONS: The cES STARFI sequence can provide simultaneous MR-ARFI and temperature measurements during pulsed HIFU applications. Though the exact displacement cannot be quantified directly, the sequence showed increased phase sensitivity compared with the spGRE sequence and provided efficient visualization of the focal spot. cES STARFI could therefore be a desirable alternative to spGRE STARFI in practical applications.

A Magnetic Resonance-Guided Focused Ultrasound Neuromodulation System With a Whole Brain Coil Array for Nonhuman Primates at 3 T.

The phased-array radio frequency (RF) coil plays a vital role in magnetic resonance-guided focused ultrasound (MRgFUS) neuromodulation studies, where accurate brain functional stimulations and neural circuit observations are required. Although various designs of phased-array coils have been reported, few are suitable for ultrasound stimulations. In this study, an MRgFUS neuromodulation system comprised of a whole brain coverage non-human primate (NHP) RF coil and an MRI-compatible ultrasound device was developed. When compared to a single loop coil, the NHP coil provided up to a 50% increase in the signal-to-noise ratio (SNR) in the brain and acquired better anatomical image-quality. The NHP coil also demonstrated the ability to achieve higher spatial resolution and reduce distortion in echo-planer imaging (EPI). Ultrasound beam characteristics and transcranial magnetic resonance acoustic radiation force (MR-ARF) were measured for simulated positions, and calculated B0 maps were employed to establish MRI-compatibility. The differences between focused off and on ultrasound techniques were measured using SNR, g-factors, and temporal SNR (tSNR) analyses and all deviations were under 2.3%. The EPI images quality and stable tSNR demonstrated the suitability of the MRgFUS neuromodulation system to conduct functional MRI studies. Last, the time course of the blood oxygen level dependent (BOLD) signal of posterior cingulate cortex in a focused ultrasound neuromodulation study was detected and repeated with MR thermometry.

Ultrasound Neuromodulation Inhibits Seizures in Acute Epileptic Monkeys.

Ultrasound stimulation has recently emerged as a non-invasive method for modulating brain activity in animal and human studies with healthy subjects. Whether brain diseases such as Alzheimer's disease, epilepsy, and depression can be treated using ultrasound stimulation still needs to be explored. Recent studies have reported that ultrasound stimulation suppressed epileptic seizures in a rodent model of epilepsy. These findings raise the crucial question of whether ultrasound stimulation can inhibit seizures in non-human primates with epilepsy. Here, we addressed this critical question. We confirmed that ultrasound stimulation significantly reduced the frequency of seizures in acute epileptic monkeys. Furthermore, the results showed that the number and duration of seizures were reduced, whereas the inter-seizure interval was increased after ultrasound stimulation. Besides, no significant brain tissue damage was observed by T2-weighted MR imaging. Our results are of great importance for future clinical applications of ultrasound neuromodulation in patients with epilepsy.

Real-time volumetric MR thermometry using 3D echo-shifted sequence under an open source reconstruction platform.

PURPOSE: The aim of this work is to implement real-time 3D MR thermometry for high intensity focused ultrasound (HIFU) monitoring. METHODS: Volumetric MR thermometry was implemented based on a 3D echo-shifted sequence with short TR to improve temperature sensitivity. The 3D acquisition was accelerated in two phase encoding directions with controlled aliasing in volumetric parallel imaging (CAIPIRINHA). Image reconstruction was run in an open source reconstruction platform (Gadgetron). RESULTS: Phantom experiments showed the proposed volumetric thermometry was comparable to the fiber optical thermometer. In-vivo animal experiments in rabbit thigh showed that the temperature error before and after 4× acceleration was less than 0.65 °C. Finally, real-time 3D thermometry with temporal resolution ~3 s and spatial resolution 2 × 2 × 5 mm3 (spatial coverage 192 × 192 × 80 mm3) was achieved with Gadgetron reconstruction. CONCLUSION: Real-time temperature monitoring was achieved in-vivo by using parallel imaging accelerated 3D echo-shifted sequence with Gadgetron reconstruction.

Imaging-guided focused ultrasound-induced thermal and sonodynamic effects of nanosonosensitizers for synergistic enhancement of glioblastoma therapy.

Glioblastoma (GBM) is a deadly brain tumor with poor prognosis and high mortality in patients. Given the low efficacy and serious side effects of current GBM therapy compared to those of conventional surgery, chemotherapy and radiation therapy, the development of a novel method for GBM management is very urgent. Sonodynamic therapy (SDT) has gained considerable attention in GBM therapy due to the advantages of deep tissue penetration and high biosafety. However, the low reactive oxygen species (ROS) generation efficacy of SDT has generally limited further applications and clinical translation. In this work, we report the simultaneous application of focused ultrasound-induced moderate thermal treatment (42 °C) and SDT for synergistic enhancement against GBM. Manganese ion (Mn2+)-chelated human serum albumin (HSA)-chlorin e6 (Ce6) nanoassemblies (HCM NAs) as targeting nanosonosensitizers were prepared using an assembly strategy. Our studies indicated that the HCM NAs had excellent T1-weighted contrast performance (12.2 mM-1 s-1) compared to that of clinically used Magnevist (4.3 mM-1 s-1) and achieved highly selective in vitro cell recognition and in vivo tumor-targeting magnetic resonance (MR) and fluorescence (FL) imaging with a signal-to-background ratio of 13.5 at 24 h post injection. Upon imaging-guided focused ultrasound irradiation, the temperature and reactive oxygen species (ROS) content of the tumor region increased simultaneously over time, achieving synergistic effects. The brain tumors were completely suppressed in subcutaneous mouse models of glioma, and the antitumor effect was greatly improved in orthotopic mouse models of glioma. It suggest that the synergistic treatment with moderate temperature and SDT induced by imaging-guided focused ultrasound is a promising platform against GMB, holds great potential in clinical settings.

Hierarchical iterative linear-fitting algorithm (HILA) for phase correction in fat quantification by bipolar multi-echo sequence.

BACKGROUND: Multi-echo gradient echo (GRE) sequence with bipolar readout gradients can reduce achievable echo spacing and thus have higher acquisition efficiency compared to unipolar readout gradients for fat fraction (FF) quantification. However, the eddy current induced phase (EC-phase) in a bipolar sequence corrupts the phase consistency between echoes and can lead to inaccurate fat quantification. METHODS: A hierarchical iterative linear-fitting algorithm (HILA) was proposed for EC-phase correction. In each iteration, image blocks were divided into sub-blocks. The EC-phase was fitted to a linear model in each sub-block. The estimated linear phase in each sub-block was then used as a starting value for the next iteration. Finally, a weighted average over all levels was calculated to obtain the final EC-phase map. Monte Carlo simulations were adopted to evaluate how the residual EC-phase would affect FF quantification accuracy. The performance of the proposed HILA method was then compared to the well-established unipolar acquisition method in phantom and in vivo experiments on 3T. RESULTS: The simulations showed that certain ΔTE values, such as ΔTE =~0.80/1.50/1.95 ms, allowed for FF estimation that were relatively robust to the residual EC-phase ranging from -2π/15 to 2π/15 for a 6-echo bipolar acquisition on 3T. The phantom study showed that the maximum mean FF error, after EC-phase correction with the proposed HILA method, was smaller than 2%, implying that HILA can approximate the high-order term of the EC-phase through step-wise linear fitting. There was no significant difference between the FFs from bipolar and unipolar acquisitions on the two MR systems in the in vivo experiments. CONCLUSIONS: The proposed HILA method provides a simple and efficient EC-phase correction method for bipolar acquisition without acquiring additional data. The appropriate choice of TEs may further reduce the effect of the residual EC-phase on accurate FF quantification with bipolar readout sequence.

Fat-water separation based on Transition REgion Extraction (TREE).

PURPOSE: To develop a method based on fat-water transition region extraction (TREE) for robust fat-water separation and quantification in challenging scenarios, including low signal-to-noise ratio (SNR), fast changing B0 field, and disjointed anatomies. THEORY AND METHODS: In TREE method, the phasor solutions of each pixel were categorized into fat-dominant and water-dominant groups. The fat-water transition region was then extracted by detecting sudden changes in the phasor maps. The phasor solutions of the pixels in the transition region were solved by choosing the smoothest phasor combinations. For the remaining subregions, the phasor solution was then determined by all the surrounding transition region pixels. The proposed method was validated using various datasets, including some from the International Society for Magnetic Resonance in Medicine (ISMRM) 2012 Challenge. RESULTS: Quantitative score of proposed method (9936.8 of 10,000) is comparable to the winner (9951.9) of ISMRM 2012 Challenge. The total processing time was 179.3 s for 15 datasets. Sagittal spine data with ~400 mm field of view in head-foot direction were used to compare TREE with several representative region-growing methods. Results showed that the proposed method was robust under fast changing B0 field, disjointed anatomies and low SNR area. No apparent fat-water swap was observed in the low SNR (SNR ~ 10) dataset. Accurate proton density fat fraction results were also produced from the proposed method. CONCLUSION: A method based on fat-water transition region extraction was proposed for robust water-fat separation and fat fraction quantification. The method worked well in spatially disjointed objects, fast changing B0 field, and low SNR application.

Dual-step iterative temperature estimation method for accurate and precise fat-referenced PRFS temperature imaging.

PURPOSE: The aim of this study was to propose dual-step iterative temperature estimation (DITE) of a fat-referenced proton resonance frequency shift (PRFS) method to improve both the accuracy and precision of temperature estimations in fat-containing tissues. METHODS: A fat-water signal model with multiple fat peaks was used to simultaneously estimate the temperature, fat/water intensity and T 2 ∗ , and field offset. In DITE, model fitting was implemented with alternating 2-step minimizations. The estimated temperature map was smoothed between the 2-step minimizations, which is considered to be the most important step for improving the temperature precision. The performance of DITE was evaluated with a Monte Carlo simulation, fat/water phantoms, and ex vivo brown adipose tissue experiments and then compared with the performance of previous fat-referenced proton resonance frequency shift methods. RESULTS: In fat/water phantom experiment with a smooth temperature profile, the temperatures estimated by DITE are consistent with the thermometer results and present a better accuracy and precision than those of previous fat-referenced proton resonance frequency shift methods. In the brown adipose tissue heating experiment, the average mean error, SD, and RMS error were -0.08ºC, 0.46ºC, and 0.56ºC, respectively, over all of the measurements within the region of interest. CONCLUSION: Our proposed DITE method improves both the accuracy and precision of temperature measurements in tissues with fat fractions between 20% and 80% under smooth distribution of the temperature profile and represents a simple fat-referenced thermometry method.

Fast MR thermometry using an echo-shifted sequence with simultaneous multi-slice imaging.

PURPOSE: Real-time monitoring is important for the safety and effectiveness of high-intensity focused ultrasound (HIFU) therapy. Magnetic resonance imaging is the preferred imaging modality for HIFU monitoring, with its unique capability of temperature imaging. For real-time temperature imaging, higher temporal resolution and larger spatial coverage are needed. In this study, a sequence based on the echo-shifted RF-spoiled gradient echo (GRE) with simultaneous multi-slice (SMS) imaging was designed for fast temperature imaging. METHODS: A phantom experiment was conducted to evaluate the accuracy of the echo-shifted sequence using a fluorescent fiber thermometer as reference. The temperature uncertainty of the echo-shifted sequence was compared with the traditional GRE sequence at room temperature through the ex vivo porcine muscle. Finally, the ex vivo porcine liver tissue experiment using HIFU heating was performed to demonstrate that the spatial coverage was increased without decreasing temporal resolution. RESULTS: The echo-shifted sequence had a better temperature uncertainty performance compared with the traditional GRE sequence with the same temporal resolution. The ex vivo heating experiment confirmed that by combining the SMS technique and echo-shifted sequence, the spatial coverage was increased without decreasing the temporal resolution while maintaining high temperature measurement precision. CONCLUSION: The proposed technique was validated as an effective real-time method for monitoring HIFU therapy.

Diffusion effect on T2 relaxometry in triple-echo steady state free precession sequence.

PURPOSE: The purpose of this study is to evaluate the effect of diffusion on SSFP (Steady-state Free Precession) signals in triple-echo steady state (TESS) sequence and ultimately on the accuracy of T2 relaxometry. METHODS: The extended phase graph (EPG) algorithm was used to study the effect of diffusion on SSFP signals and T2 relaxometry. The simulation results were verified by a commercial phantom and in vivo studies. Based on the simulation results, a correction scheme was proposed to correct the estimated T2 values. RESULTS: T2 underestimation in TESS was evident in case of small flip angle and large unbalanced gradient moment on objects with large T2 and D values. The T2 underestimation mainly originated from the diffusion sensitivity of SSFP-echo. It was also observed that SSFP-FID (Free Induction Decay) signals increased with increasing diffusion weighting under some specific conditions. The proposed correction scheme corrected the T2 underestimation, which verified that the underestimation was due to the neglect of diffusion effect. For clinical practice of TESS in tissues with short T2 such as cartilage and muscle, the diffusion effect of TESS is negligible. CONCLUSION: The effect of diffusion cannot be neglected during TESS T2 quantification as it is the main source of T2 underestimation when small flip angle and large unbalanced gradient moment is used, especially for objects with large T2 and D values.

Spatial and temporal observation of phase-shift nano-emulsions assisted cavitation and ablation during focused ultrasound exposure.

BACKGROUND: Phase-shift nano-emulsions (PSNEs) with a small initial diameter in nanoscale have the potential to leak out of the blood vessels and to accumulate at the target point of tissue. At desired location, PSNEs can undergo acoustic droplet vaporization (ADV) process, change into gas bubbles and enhance focused ultrasound efficiency. The threshold of droplet vaporization and influence of acoustic parameters have always been research hotspots in order to spatially control the potential of bioeffects and optimize experimental conditions. However, when the pressure is much higher than PSNEs' vaporization threshold, there were little reports on their cavitation and thermal effects. OBJECT: In this study, PSNEs induced cavitation and ablation effects during pulsed high-intensity focused ultrasound (HIFU) exposure were investigated, including the spatial and temporal information and the influence of acoustic parameters. METHODS: Two kinds of tissue-mimicking phantoms with uniform PSNEs were prepared because of their optical transparency. The Sonoluminescence (SL) method was employed to visualize the cavitation activities. And the ablation process was observed as the heat deposition could produce white lesion. RESULTS: Precisely controlled HIFU cavitation and ablation can be realized at a relatively low input power. But when the input power was high, PSNEs can accelerate cavitation and ablation in pre-focal region. The cavitation happened layer by layer advancing the transducer. While the lesion appeared to be separated into two parts, one in pre-focal region stemmed from one point and grew quickly, the other in focal region grew much more slowly. The influence of duty cycle has also been examined. Longer pulse off time would cause heat transfer to the surrounding media, and generate smaller lesion. On the other hand, this would give outer layer bubbles enough time to dissolve, and inner bubbles can undergo violent collapse and emit bright light.

Cavitation mapping by sonochemiluminescence with less bubble displacement induced by acoustic radiation force in a 1.2 MHz HIFU.

An acoustic radiation force counterbalanced appliance was employed to map the cavitation distribution in water. The appliance was made up of a focused ultrasound transducer and an aluminum alloy reflector with the exactly same shape. They were centrosymmetry around the focus of the source transducer. Spatial-temporal dynamics of cavitation bubble clouds in the 1.2 MHz ultrasonic field within this appliance were observed in water. And they were mapped by sonochemiluminescence (SCL) recordings and high-speed photography. There were significant differences in spatial distribution and temporal evolution between normal group and counterbalanced group. The reflector could avoid bubble directional displacement induced by acoustic radiation force under certain electric power (≤50 W). As a result, the SCL intensity in the pre-focal region was larger than that of normal group. In event of high electric power (≥70 W), most of the bubbles were moving in acoustic streaming. When electric power decreased, bubbles kept stable and showed stripe structure in SCL images. Both stationary bubbles and moving bubbles have been captured, and exhibited analytical potential with respect to bubbles in therapeutic ultrasound.

Sonochemiluminescence observation and acoustic detection of cavitation induced by pulsed HIFU at a tissue-fluid interface.

The aim of this study is to investigate the mechanism of the erosion process induced by 1.2 MHz pulsed high-intensity focused ultrasound (pulsed HIFU). By using Sonochemiluminescence (SCL) photograph, the initiation and maintenance of active cavitation were observed. In order to understand the role of both inertial cavitation and stable cavitation, a passive cavitation detection (PCD) transducer was used. Since the exposure variables of HIFU are important in the controlled ultrasound tissue erosion, the influence of pulse length (PL) and duty cycle (DC, Ton:Toff) has been examined. The results of tissue hole, SCL observation and acoustic detection revealed that the erosion was highly efficient for shorter PL. For higher DCs, the area of SCL increased with increasing PL. For lower DCs, the area of SCL increased with increasing PL from 10 to 20 µs and then kept constant. For all PLs, the intensity of SCL decreased with lower DC. For all DCs, the intensity of SCL per unit area (the ratio of SCL intensity to SCL area) also decreased with increasing PL from 10 to 80 µs, which suggested that the higher the intensity of SCL is, the higher the efficiency of tissue erosion is. At DC of 1:10, the position of the maximum pixel in SCL pictures was distant from the tissue-fluid interface with the increasing PL because of shielding effect. By the comparison of inertial cavitation dose (ICD) and the stable cavitation dose (SCD), the mechanisms associated with inertial cavitation are very likely to be the key factor of the erosion process.

Cavitation distribution within large phantom vessel and mechanical damage formed on surrounding vessel wall.

Blood vessel is one of the most important targets encountered during focused ultrasound (FU) therapy. The lasting high temperature caused by continuous FU can result in structural modification of small vessel. For the vessel with a diameter larger than 2mm, convective cooling can significantly weaken the thermal effect of FU. Meanwhile, the continued presence of ultrasound will cause repetitive cavitation and acoustic microstreaming, making comprehension of continuous wave induced cavitation effect in large vessels necessary. The Sonoluminescence (SL) method, mechanical damage observation and high-speed camera were used in this study to investigate the combination effect of ultrasound contrast agents (UCAs) and continuous FU in large phantom vessels with a diameter of 10mm without consideration of thermal effect. When the focus was positioned at the proximal wall, cylindrical hole along the acoustic axis opposite the ultrasound wave propagation direction was observed at the input power equal to or greater than 50 W. When the focus was located at the distal wall, only small tunnels can be found. The place where the cylindrical hole formed was corresponding to where bubbles gathered and emitted brilliant light near the wall. Without UCAs neither such bright SL nor cylindrical hole can be found. However, the UCAs concentration had little influence on the SL distribution and the length of cylindrical hole. The SL intensity near the proximal vessel wall and the length of the cylindrical hole both increased with the input power. It is suggested that these findings need to be considered in the large vessel therapy and UCAs usage.

Sonochemiluminescence observation of lipid- and polymer-shelled ultrasound contrast agents in 1.2 MHz focused ultrasound field.

Ultrasound contrast agents (UCAs) are frequently added into the focused ultrasound field as cavitation nuclei to enhance the therapeutic efficiency. Since their presence will distort the pressure field and make the process unpredictable, comprehension of their behaviors especially the active zone spatial distribution is an important part of better monitoring and using of UCAs. As shell materials can strongly alter the acoustic behavior of UCAs, two different shells coated UCAs, lipid-shelled and polymer-shelled UCAs, in a 1.2 MHz focused ultrasound field were studied by the Sonochemiluminescence (SCL) method and compared. The SCL spatial distribution of lipid-shelled group differed from that of polymer-shelled group. The shell material and the character of focused ultrasound field work together to the SCL distribution, causing the lipid-shelled group to have a maximum SCL intensity in pre-focal region at lower input power than that of polymer-shelled group, and a brighter SCL intensity in post-focal region at high input power. The SCL inactive area of these two groups both increased with the input power. The general behavior of the UCAs can be studied by both the average SCL intensity and the backscatter signals. As polymer-shelled UCAs are more resistant to acoustic pressure, they had a higher destruction power and showed less reactivation than lipid-shelled ones.