FUS (focused ultrasound), or HIFU (high-intensity-focused ultrasound) therapy, a minimally or non-invasive procedure that uses ultrasound to generate thermal necrosis, has been proven successful in several clinical applications. This paper discusses a method for monitoring thermal treatment at different sonication durations (10 s, 20 s and 30 s) using the amplitude-modulated (AM) harmonic motion imaging for focused ultrasound (HMIFU) technique in bovine liver samples in vitro. The feasibility of HMI for characterizing mechanical tissue properties has previously been demonstrated. Here, a confocal transducer, combining a 4.68 MHz therapy (FUS) and a 7.5 MHz diagnostic (pulse-echo) transducer, was used. The therapy transducer was driven by a low-frequency AM continuous signal at 25 Hz, producing a stable harmonic radiation force oscillating at the modulation frequency. A pulser/receiver was used to drive the pulse-echo transducer at a pulse repetition frequency (PRF) of 5.4 kHz. Radio-frequency (RF) signals were acquired using a standard pulse-echo technique. The temperature near the ablation region was simultaneously monitored. Both RF signals and temperature measurements were obtained before, during and after sonication. The resulting axial tissue displacement was estimated using one-dimensional cross correlation. When temperature at the focal zone was above 48 degrees C during heating, the coagulation necrosis occurred and tissue damage was irreversible. The HMI displacement profiles in relation to the temperature and sonication durations were analyzed. At the beginning of heating, the temperature at the focus increased sharply, while the tissue stiffness decreased resulting in higher HMI displacements. This was confirmed by an increase of 0.8 microm degrees C(-1)(r=0.93, p<.005). After sustained heating, the tissue became irreversibly stiffer, followed by an associated decrease in the HMI displacement (-0.79 microm degrees C(-1), r=-0.92, p<0.001). Repeated experiments showed a reproducible pattern of the HMI displacement changes with a temperature at a slope equal to 0.8+/-0.11 and -0.79+/-0.14 microm degrees C(-1), prior to and after lesion formation in seven bovine liver samples, respectively. This technique was thus capable of following the protein-denatured lesion formation based on the variation of the HMI displacements. This method could, therefore, be applied for real-time monitoring of temperature-related stiffness changes of tissues during FUS, HIFU or other thermal therapies.

Quantifying the mechanical properties of soft tissues remains a challenging objective in the field of elasticity imaging. In this work, we propose an ultrasound-based method for quantitatively estimating viscoelastic properties, using the amplitude-modulated harmonic motion imaging (HMI) technique. In HMI, an oscillating acoustic radiation force is generated inside the medium by using focused ultrasound and the resulting displacements are measured using an imaging transducer. The proposed approach is a two-step method that uses both the properties of the propagating shear wave and the phase shift between the applied stress and the measured strain in order to infer to the shear storage (G') and shear loss modulus (G''), which refer to the underlying tissue elasticity and viscosity, respectively. The proposed method was first evaluated on numerical phantoms generated by finite-element simulations, where a very good agreement was found between the input and the measured values of G' and G''. Experiments were then performed on three soft tissue-mimicking gel phantoms. HMI measurements were compared to rotational rheometry (dynamic mechanical analysis), and very good agreement was found at the only overlapping frequency (10 Hz) in the estimate of the shear storage modulus G' (14% relative error, averaged p-value of 0.34), whereas poorer agreement was found in G'' (55% relative error, averaged p-value of 0.0007), most likely due to the significantly lower values of G'' of the gel phantoms, posing thus a greater challenge in the sensitivity of the method. Nevertheless, this work proposes an original model-independent ultrasound-based elasticity imaging method that allows for direct, quantitative estimation of tissue viscoelastic properties, together with a validation against mechanical testing.

The harmonic motion imaging (HMI) technique for simultaneous monitoring and generation of ultrasound therapy using two separate focused ultrasound transducer elements was previously demonstrated. In this study, a new HMI technique is described that images tissue displacement induced by a harmonic radiation force using a single focused-ultrasound element. A wave propagation simulation model first indicated that, unlike in the two-beam configuration, the amplitude-modulated beam produced a stable focal zone for the applied harmonic radiation force. The AM beam thus offered the unique advantage of sustaining the application of the spatially-invariant radiation force. Experiments were performed on gelatin phantoms and ex vivo tissues. The radiation force was generated by a 4.68 MHz focused ultrasound (FUS) transducer using a 50 Hz amplitude-modulated wave. A 7.5 MHz pulse-echo transducer was used to acquire rf echoes during the application of the harmonic radiation force. Consecutive rf echoes were acquired with a pulse repetition frequency (PRF) of 6.5 kHz and 1D cross-correlation was performed to estimate the resulting axial tissue displacement. The HMI technique was shown capable of estimating stiffness-dependent displacement amplitudes. Finally, taking advantage of the real-time capability of the HMI technique, temperature-dependent measurements enabled monitoring ofHIFU sonication in ex vivo tissues. The new HMI method may thus enable a highly-localized force and stiffness-dependent measurements as well as real-time and low-cost HIFU monitoring.

In this study, the Harmonic Motion Imaging for Focused Ultrasound (HMIFU) technique is applied to monitor changes in mechanical properties of tissues during thermal therapy in a transgenic breast cancer mouse model in vivo. An HMIFU system, composed of a 4.5-MHz focused ultrasound (FUS) and a 3.3-MHz phased-array imaging transducer, was mechanically moved to image and ablate the entire tumor. The FUS transducer was driven by an amplitude-modulated (AM) signal at 15 Hz. The acoustic intensity ( I(spta)) was equal to 1050 W/cm(2) at the focus. A digital low-pass filter was used to filter out the spectrum of the FUS beam and its harmonics prior to displacement estimation. The resulting axial displacement was estimated using 1-D cross-correlation on the acquired RF signals. Results from two mice with eight lesions formed in each mouse (16 lesions total) showed that the average peak-to-peak displacement amplitude before and after lesion formation was respectively equal to 17.34 +/- 1.34 microm and 10.98 +/- 1.82 microm ( p << 0.001). Cell death was also confirmed by hematoxylin and eosin histology. HMI displacement can be used to monitor the relative tissue stiffness changes in real time during heating so that the treatment procedure can be performed in a time-efficient manner. The HMIFU system may, therefore, constitute a cost-efficient and reliable alternative for real-time monitoring of thermal ablation.

A mesoporous aluminophosphate support, meso-AlPO, was synthesized by phosphate treatment of an AlO4Al12(OH)24(H2O) 7+ cluster/dodecyl sulfate salt, followed by extraction of the surfactant with an acetate/ methanol solution. The meso-AlPO product was shown to be an effective anion exchange material. Anion exchange capacities for chromate and several monoanionic and dianionic organic dyes fell in the range from approximately 1.3-1.6 meq/g. Control experiments with the neutral support MCM-41 and a nonionic dye indicated that anion adsorption in meso-AlPO was caused predominantly by electrostatic interactions rather than pure physisorption. Multiple exchanges were possible if the support was regenerated by acid treatment at pH 4.3. While the material exhibited size-selectivity for anionic dyes, the average pore sizes increased during anion exchanges in aqueous solutions. The mesopore structure of meso-AlPO was thermally stable up to 200 °C, and anion exchanges at 100 °C under aqueous reflux resulted in similar exchange capacities as room-temperature exchanges.