State of the art on microbubble cavitation monitoring and feedback control for blood-brain-barrier opening using focused ultrasound.

Focused ultrasound (FUS) is a non-invasive and highly promising method for targeted and reversible blood-brain barrier permeabilization. Numerous preclinical studies aim to optimize the localized delivery of drugs using this method in rodents and non-human primates. Several clinical trials have been initiated to treat various brain diseases in humans using simultaneous BBB permeabilization and drug injection. This review presents the state of the art ofin vitroandin vivocavitation control algorithms for BBB permeabilization using microbubbles (MB) and FUS. Firstly, we describe the different cavitation states, their physical significance in terms of MB behavior and their translation into the spectral composition of the backscattered signal. Next, we report the different indexes calculated and used during the ultrasonic monitoring of cavitation. Finally, the differentin vitroandin vivocavitation control strategies described in the literature are presented and compared.

Magnetic Resonance Acoustic Radiation Force Imaging (MR-ARFI) for the monitoring of High Intensity Focused Ultrasound (HIFU) ablation in anisotropic tissue.

OBJECTIVE: We introduce a non-invasive MR-Acoustic Radiation Force Imaging (ARFI)-based elastography method that provides both the local shear modulus and temperature maps for the monitoring of High Intensity Focused Ultrasound (HIFU) therapy. MATERIALS AND METHODS: To take tissue anisotropy into account, the local shear modulus µ is determined in selected radial directions around the focal spot by fitting the phase profiles to a linear viscoelastic model, including tissue-specific mechanical relaxation time τ. MR-ARFI was evaluated on a calibrated phantom, then applied to the monitoring of HIFU in a gel phantom, ex vivo and in vivo porcine muscle tissue, in parallel with MR-thermometry. RESULTS: As expected, the shear modulus polar maps reflected the isotropy of phantoms and the anisotropy of muscle. In the HIFU monitoring experiments, both the shear modulus polar map and the thermometry map were updated with every pair of MR-ARFI phase images acquired with opposite MR-ARFI-encoding. The shear modulus was found to decrease (phantom and ex vivo) or increase (in vivo) during heating, before remaining steady during the cooling phase. The mechanical relaxation time, estimated pre- and post-HIFU, was found to vary in muscle tissue. DISCUSSION: MR-ARFI allowed for monitoring of viscoelasticity changes around the HIFU focal spot even in anisotropic muscle tissue.

Monitoring MR-guided high intensity focused ultrasound therapy using transient supersonic shear wave MR-elastography.

Objective.The aim of the paper is to propose an all-in-one method based on magnetic resonance-supersonic shear wave imaging (MR-SSI) and proton resonance frequency shift (PRFS) to monitor high intensity focused ultrasound (HIFU) thermal ablations.Approach.Mechanical properties have been shown to be related to tissue damage induced by thermal ablations. Monitoring elasticity in addition to temperature changes may help in ensuring the efficacy and the accuracy of HIFU therapies. For this purpose, an MR-SSI method has been developed where the ultrasonic transducer is used for both mechanical wave generation and thermal ablation. Transient quasi-planar shear waves are generated using the acoustic radiation force, and their propagation is monitored in motion-sensitized phase MR images. Using a single-shot gradient-echo echo-planar-imaging sequence, MR images can be acquired at a sufficiently high temporal resolution to provide an update of PRFS thermometry and MR-SSI elastography maps in real time.Main results.The proposed method was first validated on a calibrated elasticity phantom, in which both the possibility to detect inclusions with different stiffness and repeatability were demonstrated. The standard deviation between the 8 performed measurements was 2% on the background of the phantom and 11%, at most, on the inclusions. A second experiment consisted in performing a HIFU heating in a gelatin phantom. The temperature increase was estimated to be 9 °C and the shear modulus was found to decrease from 2.9 to 1.8 kPa, reflecting the gel softening around the HIFU focus, whereas it remained steady in non-heated areas.Significance.The proposed MR-SSI technique allows monitoring HIFU ablations using thermometry and elastography simultaneously, without the need for an additional external mechanical exciter such as those used in MR elastography.

A new versatile MR-guided high-intensity focused ultrasound (HIFU) device for the treatment of musculoskeletal tumors.

Magnetic Resonance (MR) Imaging-guided High Intensity focused Ultrasound (MRgHIFU) is a non-invasive, non-ionizing thermal ablation therapy that is particularly interesting for the palliative or curative treatment of musculoskeletal tumors. We introduce a new modular MRgHIFU device that allows the ultrasound transducer to be positioned precisely and interactively over the body part to be treated. A flexible, MR-compatible supporting structure allows free positioning of the transducer under MRI/optical fusion imaging guidance. The same structure can be rigidified using pneumatic depression, holding the transducer rigidly in place. Targeting accuracy was first evaluated in vitro. The average targeting error of the complete process was found to be equal to 5.4 ± 2.2 mm in terms of focus position, and 4.7° ± 2° in terms of transducer orientation. First-in-man feasibility is demonstrated on a patient suffering from important, uncontrolled pain from a bone metastasis located in the forearm. The 81 × 47 × 34 mm3 lesion was successfully treated using five successive positions of the transducer, under real-time monitoring by MR Thermometry. Significant pain palliation was observed 3 days after the intervention. The system described and characterized in this study is a particularly interesting modular, low-cost MRgHIFU device for musculoskeletal tumor therapy.

Influence of portal vein occlusion on portal flow and liver elasticity in an animal model.

Hepatic fibrosis causes an increase in liver stiffness, a parameter measured by elastography and widely used as a diagnosis method. The concomitant presence of portal vein thrombosis (PVT) implies a change in hepatic portal inflow that could also affect liver elasticity. The main objective of this study is to determine the extent to which the presence of portal occlusion can affect the mechanical properties of the liver and potentially lead to misdiagnosis of fibrosis and hepatic cirrhosis by elastography. Portal vein occlusion was generated by insertion and inflation of a balloon catheter in the portal vein of four swines. The portal flow parameters peak flow (PF) and peak velocity magnitude (PVM) and liver mechanical properties (shear modulus) were then investigated using 4D-flow MRI and MR elastography, respectively, for progressive obstructions of the portal vein. Experimental results indicate that the reduction of the intrahepatic venous blood flow (PF/PVM decreases of 29.3%/8.5%, 51.0%/32.3% and 83.3%/53.6%, respectively) measured with 50%, 80% and 100% obstruction of the portal vein section results in a decrease of liver stiffness by 0.8% ± 0.1%, 7.7% ± 0.4% and 12.3% ± 0.9%, respectively. While this vascular mechanism does not have sufficient influence on the elasticity of the liver to modify the diagnosis of severe fibrosis or cirrhosis (F4 METAVIR grade), it may be sufficient to attenuate the increase in stiffness due to moderate fibrosis (F2-F3 METAVIR grades) and consequently lead to false-negative diagnoses with elastography in the presence of PVT.

Planning Framework for Robot-assisted Blood-Brain Barrier Opening with Focused Ultrasound.

This article presents a method to plan BloodBrain Barrier (BBB) disruption with Focused Ultrasound, under neuronavigated robotic assistance. Robotic and acoustic constraints are defined to estimate brain target accessibility. The relevance of the proposed framework is illustrated in specific brain target examples.

Simultaneous fat-referenced proton resonance frequency shift thermometry and MR elastography for the monitoring of thermal ablations.

PURPOSE: Simultaneous fat-referenced proton resonance frequency shift (FRPRFS) thermometry combined with MR elastography (MRE) is proposed, to continuously monitor thermal ablations for all types of soft tissues, including fat-containing tissues. Fat-referenced proton resonance frequency shift thermometry makes it possible to measure temperature even in the water fraction of fat-containing tissues while enabling local field-drift correction. Magnetic resonance elastography allows measuring the mechanical properties of tissues that are related to tissue structural damage. METHODS: A gradient-echo MR sequence framework was proposed that combines the need for multiple TE acquisitions for the water-fat separation of FRPRFS, and the need for multiple MRE phase offsets for elastogram reconstructions. Feasibility was first assessed in a fat-containing gelatin phantom undergoing moderate heating by a hot water circulation system. Subsequently, high intensity focused ultrasound heating was conducted in porcine muscle tissue ex vivo (N = 4; 2 samples, 2 locations/sample). RESULTS: Both FRPRFS temperature maps and elastograms were updated every 4.1 seconds. In the gelatin phantom, FRPRFS was in good agreement with optical fiber thermometry (average difference 1.2 ± 1°C). In ex vivo high-intensity focused ultrasound experiments on muscle tissue, the shear modulus was found to decrease significantly by 34.3% ± 7.7% (experiment 1, sample 1), 17.9% ± 10.0% (experiment 2, sample 1), 55.1% ± 8.7% (experiment 3, sample 2), and 34.7% ± 8.4% (experiment 4, sample 2) as a result of temperature increase (ΔT = 22.5°C ± 4.2°C, 14.0°C ± 2.8°C, 14.7°C ± 3.7°C, and 14.5°C ± 3.0°C, respectively). CONCLUSION: This study demonstrated the feasibility of monitoring thermal ablations with FRPRFS thermometry together with MRE, even in fat-containing tissues. The acquisition time is similar to non-FRPRFS thermometry combined with MRE.

Accuracy of a CT-Ultrasound Fusion Imaging Guidance System Used for Hepatic Percutaneous Procedures.

PURPOSE: To evaluate the accuracy of a fusion imaging guidance system using ultrasound (US) and computerized tomography (CT) as a real-time imaging modality for the positioning of a 22-gauge needle in the liver. MATERIALS AND METHODS: The spatial coordinates of 23 spinal needles placed at the border of hepatic tumors before radiofrequency thermal ablation were determined in 23 patients. Needles were inserted up to the border of the tumor with the use of CT-US fusion imaging. A control CT scan was carried out to compare real (x, y, z) and virtual (x', y', z') coordinates of the tip of the needle (D for distal) and of a point on the needle located 3 cm proximally to the tip (P for proximal). RESULTS: The mean Euclidian distances were 8.5 ± 4.7 mm and 10.5 ± 5.3 mm for D and P, respectively. The absolute value of mean differences of the 3 coordinates (|x' - x|, |y' - y|, and |z' - z|) were 4.06 ± 0.9, 4.21 ± 0.84, and 4.89 ± 0.89 mm for D and 3.96 ± 0.60, 4.41 ± 0.86, and 7.66 ± 1.27 mm for P. X = |x' - x| and Y = |y' - y| coordinates were <7 mm with a probability close to 1. Z = |z' - z| coordinate was not considered to be larger nor smaller than 7 mm (probability >7 mm close to 50%). CONCLUSIONS: Positioning errors with the use of US-CT fusion imaging used in this study are not negligible for the insertion of a 22-gauge needle in the liver. Physicians must be aware of such possible errors to adapt the treatment when used for thermal ablation.

Targetability of osteoid osteomas and bone metastases by MR-guided high intensity focused ultrasound (MRgHIFU).

PURPOSE: To retrospectively evaluate the suitability of MRgHIFU for osteoid osteomas (OOs) and bone metastases in patients who underwent minimally-invasive percutaneous thermal ablation. MATERIALS AND METHODS: One hundred and sixty-seven lesions (115 metastases and 52 OOs) treated percutaneously between October 2014 and June 2017 were retrospectively analyzed. Tumors were located in the spine or sacrum (54), pelvis (43), limbs (50), ribs (17) and sternum (3). Tumor volume, matrix, anatomical environment and need for protection of surrounding structures or consolidation were assessed. Cases were classified into three categories: (a) lesions suitable for MRgHIFU therapy alone; (b) lesions suitable for MRgHIFU if protection of surrounding structures and/or bone consolidation is performed; (c) lesions not suitable for MRgHIFU. RESULTS: Twenty-six (50%) of OOs were classified as suitable for MRgHIFU alone and 17 (32.7%) as suitable for MRgHIFU with hydro-dissection. Matrix of treatable OOs was sclerotic (19), lytic (15) or mixed (9), with mean volume 0.56 cm3. Forty-one (35.7%) of metastases were classified as suitable for MRgHIFU alone and 43 (37.4%) as suitable with hydro-dissection and/or consolidation. Matrix of metastases was sclerotic (13), lytic (37) or mixed (34), with mean volume 71.9 cm3. Mean depth of targetable lesions was 50.9 ± 28.4 mm. 97.7% of pelvic lesions and 94% of peripheral bone lesions were targetable by HIFU. 66.6% of spinal or sacral lesions were considered untreatable. CONCLUSION: MRgHIFU cannot be systematically performed non-invasively on bone tumors. Combination with minimally-invasive thermo-protective techniques may increase the number of eligible cases.

MR-ARFI-based method for the quantitative measurement of tissue elasticity: application for monitoring HIFU therapy.

Monitoring thermal therapies through medical imaging is essential in order to ensure that they are safe, efficient and reliable. In this paper, we propose a new approach, halfway between MR acoustic radiation force imaging (MR-ARFI) and MR elastography (MRE), allowing for the quantitative measurement of the elastic modulus of tissue in a highly localized manner. It relies on the simulation of the MR-ARFI profile, which depends on tissue biomechanical properties, and on the identification of tissue elasticity through the fitting of experimental displacement images measured using rapid MR-ARFI. This method was specifically developed to monitor MR-guided high intensity focused ultrasound (MRgHIFU) therapy. Elasticity changes were followed during HIFU ablations (N = 6) performed ex vivo in porcine muscle samples, and were compared to temperature changes measured by MR-thermometry. Shear modulus was found to increase consistently and steadily a few seconds after the heating started, and such changes were found to be irreversible. The shear modulus was found to increase from 1.49 ± 0.48 kPa (before ablation) to 3.69 ± 0.93 kPa (after ablation and cooling). Thanks to its ability to perform quantitative elasticity measurements in a highly localized manner around the focal spot, this method proved to be particularly attractive for monitoring HIFU ablations.

K-space data processing for magnetic resonance elastography (MRE).

OBJECTIVE: Magnetic resonance elastography (MRE) requires substantial data processing based on phase image reconstruction, wave enhancement, and inverse problem solving. The objective of this study is to propose a new, fast MRE method based on MR raw data processing, particularly adapted to applications requiring fast MRE measurement or high elastogram update rate. MATERIALS AND METHODS: The proposed method allows measuring tissue elasticity directly from raw data without prior phase image reconstruction and without phase unwrapping. Experimental feasibility is assessed both in a gelatin phantom and in the liver of a porcine model in vivo. Elastograms are reconstructed with the raw MRE method and compared to those obtained using conventional MRE. In a third experiment, changes in elasticity are monitored in real-time in a gelatin phantom during its solidification by using both conventional MRE and raw MRE. RESULTS: The raw MRE method shows promising results by providing similar elasticity values to the ones obtained with conventional MRE methods while decreasing the number of processing steps and circumventing the delicate step of phase unwrapping. Limitations of the proposed method are the influence of the magnitude on the elastogram and the requirement for a minimum number of phase offsets. CONCLUSION: This study demonstrates the feasibility of directly reconstructing elastograms from raw data.

An automatic differentiation-based gradient method for inversion of the shear wave equation in magnetic resonance elastography: specific application in fibrous soft tissues.

Quantitative and accurate measurement of in vivo mechanical properties using dynamic elastography has been the scope of many research efforts over the past two decades. Most of the shear-wave-based inverse approaches for magnetic resonance elastography (MRE) make the assumption of isotropic viscoelasticity. In this paper, we propose a quantitative gradient method for inversion of the shear wave equation in anisotropic media derived from a full waveform description using analytical viscoelastic Green formalism and automatic differentiation. The abilities and performances of the proposed identification method are first evaluated on numerical phantoms calculated in a transversely isotropic medium, and subsequently on experimental MRE data measured on an isotropic hydrogel phantom, on an anisotropic cryogel phantom and on an ex vivo fibrous muscle. The experiments are carried out by coupling circular shear wave profiles generated by acoustic radiation force and MRE acquisition of the wave front. Shear modulus values obtained by our MRE method are compared to those obtained by rheometry in the isotropic hydrogel phantom, and are found to be in good agreement despite non-overlapping frequency ranges. Both the cryogel and the ex vivo muscle are found to be anisotropic. Stiffness values in the longitudinal direction are found to be 1.8 times and 1.9 times higher than those in the transverse direction for the cryogel and the muscle, respectively. The proposed method shows great perspectives and substantial benefits for the in vivo quantitative investigation of complex mechanical properties in fibrous soft tissues.

Interventional MR elastography for MRI-guided percutaneous procedures.

PURPOSE: MRI-guided thermal ablations require reliable monitoring methods to ensure complete destruction of the diseased tissue while avoiding damage to the surrounding healthy tissue. Based on the fact that thermal ablations result in substantial changes in biomechanical properties, interventional MR elastography (MRE) dedicated to the monitoring of MR-guided thermal therapies is proposed here. METHODS: Interventional MRE consists of a needle MRE driver, a fast and interactive gradient echo pulse sequence with motion encoding, and an inverse problem solver in real-time. This complete protocol was tested in vivo on swine and the ability to monitor elasticity changes in real-time was assessed in phantom. RESULTS: Thanks to a short repetition time, a reduction of the number of phase-offsets and the use of a sliding window, one refreshed elastogram was provided every 2.56 s for an excitation frequency of 100 Hz. In vivo elastograms of swine liver were successfully provided in real-time during one breath-hold. Changes of elasticity were successfully monitored in a phantom during its gelation with the same elastogram frame rate. CONCLUSION: This study demonstrates the ability of detecting elasticity changes in real-time and providing elastograms in vivo with interventional MRE that could be used for the monitoring of thermal ablations.

Non-contact, ultrasound-based indentation method for measuring elastic properties of biological tissues using harmonic motion imaging (HMI).

Noninvasive measurement of mechanical properties of biological tissues in vivo could play a significant role in improving the current understanding of tissue biomechanics. In this study, we propose a method for measuring elastic properties non-invasively by using internal indentation as generated by harmonic motion imaging (HMI). In HMI, an oscillating acoustic radiation force is produced by a focused ultrasound transducer at the focal region, and the resulting displacements are estimated by tracking radiofrequency signals acquired by an imaging transducer. In this study, the focal spot region was modeled as a rigid cylindrical piston that exerts an oscillatory, uniform internal force to the underlying tissue. The HMI elastic modulus EHMI was defined as the ratio of the applied force to the axial strain measured by 1D ultrasound imaging. The accuracy and the precision of the EHMI estimate were assessed both numerically and experimentally in polyacrylamide tissue-mimicking phantoms. Initial feasibility of this method in soft tissues was also shown in canine liver specimens in vitro. Very good correlation and agreement was found between the measured Young's modulus and the HMI modulus in the numerical study (r(2) > 0.99, relative error <10%) and on polyacrylamide gels (r(2) = 0.95, relative error <24%). The average HMI modulus on five liver samples was found to EHMI = 2.62  ±  0.41 kPa, compared to EMechTesting = 4.2  ±  2.58 kPa measured by rheometry. This study has demonstrated for the first time the initial feasibility of a non-invasive, model-independent method to estimate local elastic properties of biological tissues at a submillimeter scale using an internal indentation-like approach. Ongoing studies include in vitro experiments in a larger number of samples and feasibility testing in in vivo models as well as pathological human specimens.

Robotized High Intensity Focused Ultrasound (HIFU) system for treatment of mobile organs using motion tracking by ultrasound imaging: An in vitro study.

High Intensity Focused Ultrasound (HIFU) therapy is a very promising method for ablation of solid tumors. However, intra-abdominal organ motion, principally due to breathing, is a substantial limitation that results in incorrect tumor targeting. The objective of this work is to develop an all-in-one robotized HIFU system that can compensate motion in real-time during HIFU treatment. To this end, an ultrasound visual servoing scheme working at 20 Hz was designed. It relies on the motion estimation by using a fast ultrasonic speckle tracking algorithm and on the use of an interleaved imaging/HIFU sonication sequence for avoiding ultrasonic wave interferences. The robotized HIFU system was tested on a sample of chicken breast undergoing a vertical sinusoidal motion at 0.25 Hz. Sonications with and without motion compensation were performed in order to assess the effect of motion compensation on thermal lesions induced by HIFU. Motion was reduced by more than 80% thanks to this ultrasonic visual servoing system.

Comparison of four different techniques to evaluate the elastic properties of phantom in elastography: is there a gold standard?

Elastographic techniques used in addition to imaging techniques (ultrasound, resonance magnetic or optical) provide new clinical information on the pathological state of soft tissues. However, system-dependent variation in elastographic measurements may limit the clinical utility of these measurements by introducing uncertainty into the measurement. This work is aimed at showing differences in the evaluation of the elastic properties of phantoms performed by four different techniques: quasi-static compression, dynamic mechanical analysis, vibration-controlled transient elastography and hyper-frequency viscoelastic spectroscopy. Four Zerdine® gel materials were tested and formulated to yield a Young's modulus over the range of normal and cirrhotic liver stiffnesses. The Young's modulus and the shear wave speed obtained with each technique were compared. Results suggest a bias in elastic property measurement which varies with systems and highlight the difficulty in finding a reference method to determine and assess the elastic properties of tissue-mimicking materials. Additional studies are needed to determine the source of this variation, and control for them so that accurate, reproducible reference standards can be made for the absolute measurement of soft tissue elasticity.

Magnetic resonance- and ultrasound imaging-based elasticity imaging methods: a review.

Elasticity imaging methods aim at measuring the mechanical behavior of soft tissues by using medical imaging modalities, such as ultrasonography or magnetic resonance imaging. The initial motivation behind these techniques, and still the main one, is the need for new diagnostic tools based on the visualization of tissue stiffness. Recent developments have demonstrated the potential that elasticity imaging methods can offer in new fields other than direct medical diagnosis, such as the field of in vivo biomechanical characterization. After a short description of the general principles behind elasticity imaging, this review illustrates some of the most original clinical applications. The use of elastography for quantitative mechanical characterization is particularly emphasized, and original applications of these methods to several biomedical research fields are reviewed.

Harmonic Motion Imaging (HMI) for Tumor Imaging and Treatment Monitoring.

Palpation is an established screening procedure for the detection of several superficial cancers including breast, thyroid, prostate, and liver tumors through both self and clinical examinations. This is because solid masses typically have distinct stiffnesses compared to the surrounding normal tissue. In this paper, the application of Harmonic Motion Imaging (HMI) for tumor detection based on its stiffness as well as its relevance in thermal treatment is reviewed. HMI uses a focused ultrasound (FUS) beam to generate an oscillatory acoustic radiation force for an internal, non-contact palpation to internally estimate relative tissue hardness. HMI studies have dealt with the measurement of the tissue dynamic motion in response to an oscillatory acoustic force at the same frequency, and have been shown feasible in simulations, phantoms, ex vivo human and bovine tissues as well as animals in vivo. Using an FUS beam, HMI can also be used in an ideal integration setting with thermal ablation using high-intensity focused ultrasound (HIFU), which also leads to an alteration in the tumor stiffness. In this paper, a short review of HMI is provided that encompasses the findings in all the aforementioned areas. The findings presented herein demonstrate that the HMI displacement can accurately depict the underlying tissue stiffness, and the HMI image of the relative stiffness could accurately detect and characterize the tumor or thermal lesion based on its distinct properties. HMI may thus constitute a non-ionizing, cost-efficient and reliable complementary method for noninvasive tumor detection, localization, diagnosis and treatment monitoring.

Performance assessment of HIFU lesion detection by harmonic motion imaging for focused ultrasound (HMIFU): a 3-D finite-element-based framework with experimental validation.

Harmonic motion imaging for focused ultrasound (HMIFU) is a novel high-intensity focused ultrasound (HIFU) therapy monitoring method with feasibilities demonstrated in vitro, ex vivo and in vivo. Its principle is based on amplitude-modulated (AM) - harmonic motion imaging (HMI), an oscillatory radiation force used for imaging the tissue mechanical response during thermal ablation. In this study, a theoretical framework of HMIFU is presented, comprising a customized nonlinear wave propagation model, a finite-element (FE) analysis module and an image-formation model. The objective of this study is to develop such a framework to (1) assess the fundamental performance of HMIFU in detecting HIFU lesions based on the change in tissue apparent elasticity, i.e., the increasing Young's modulus, and the HIFU lesion size with respect to the HIFU exposure time and (2) validate the simulation findings ex vivo. The same HMI and HMIFU parameters as in the experimental studies were used, i.e., 4.5-MHz HIFU frequency and 25 Hz AM frequency. For a lesion-to-background Young's modulus ratio of 3, 6 and 9, the FE and estimated HMI displacement ratios were equal to 1.83, 3.69 and 5.39 and 1.65, 3.19 and 4.59, respectively. In experiments, the HMI displacement followed a similar increasing trend of 1.19, 1.28 and 1.78 at 10-s, 20-s and 30-s HIFU exposure, respectively. In addition, moderate agreement in lesion size growth was found in both simulations (16.2, 73.1 and 334.7 mm(2)) and experiments (26.2, 94.2 and 206.2 mm(2)). Therefore, the feasibility of HMIFU for HIFU lesion detection based on the underlying tissue elasticity changes was verified through the developed theoretical framework, i.e., validation of the fundamental performance of the HMIFU system for lesion detection, localization and quantification, was demonstrated both theoretically and ex vivo.

Physiologic cardiovascular strain and intrinsic wave imaging.

Cardiovascular disease remains the primary killer worldwide. The heart, essentially an electrically driven mechanical pump, alters its mechanical and electrical properties to compensate for loss of normal mechanical and electrical function. The same adjustment also is performed in the vessels, which constantly adapt their properties to accommodate mechanical and geometrical changes related to aging or disease. Real-time, quantitative assessment of cardiac contractility, conduction, and vascular function before the specialist can visually detect it could be feasible. This new physiologic data could open up interactive therapy regimens that are currently not considered. The eventual goal of this technology is to provide a specific method for estimating the position and severity of contraction defects in cardiac infarcts or angina. This would improve care and outcomes as well as detect stiffness changes and overcome the current global measurement limitations in the progression of vascular disease, at little more cost or risk than that of a clinical ultrasound.