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.

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.

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.

Liver stiffness assessment by tagged MRI of cardiac-induced liver motion.

Cirrhosis is an important and growing public health problem, affecting millions of Americans and many more people internationally. A pathological hallmark of the progression to cirrhosis is the development of liver fibrosis, so that monitoring the appearance and progression of liver fibrosis can be used to guide therapy. Here, we report a method to use magnetization-tagged magnetic resonance imaging to measure the cardiac-induced motion and deformation in the liver, as a means for noninvasively assessing liver stiffness, which is related to fibrosis. The initial results show statistically significant differences between healthy and cirrhotic subjects in the direct comparisons of the maximum displacement (mm), and the maximum (P1) and minimum (P2) two-dimensional strains, through the cardiac cycle (3.514 ± 0.793, 2.184 ± 0.611; 0.116 ± 0.043, 0.048 ± 0.011; -0.094 ± 0.020, -0.041 ± 0.015; healthy, cirrhosis, respectively; P < 0.005 for all). There are also significant differences in the displacement-normalized P1 and P2 strains (mm(-1) ) (0.030 ± 0.008, 0.017 ± 0.007; -0.024 ± 0.006, -0.013 ± 0.004; healthy, cirrhosis, respectively; P < 0.005 for all). Therefore, this noninvasive imaging-based method is a promising means to assess liver stiffness using clinically available imaging tools.

In vivo preclinical low-field MRI monitoring of tumor growth following a suicide-gene therapy in an orthotopic mice model of human glioblastoma.

PURPOSE: The aim of this study was to monitor in vivo with low field MRI growth of a murine orthotopic glioma model following a suicide gene therapy. METHODS: The gene therapy consisted in the stereotactic injection in the mice brain of a modified vaccinia virus Ankara (MVA) vector encoding for a suicide gene (FCU1) that transforms a non toxic prodrug 5-fluorocytosine (5-FC) to its highly cytotoxic derivatives 5-fluorouracil (5-FU) and 5'-fluorouridine-5'monophosphate (5'-FUMP). Using a warmed-up imaging cell, sequential 3D T1 and T2 0.1T MRI brain examinations were performed on 16 Swiss female nu/nu mice bearing orthotopic human glioblastoma (U87-MG cells). The 6-week in vivo MRI follow-up consisted in a weekly measurement of the intracerebral tumor volume leading to a total of 65 examinations. Mice were divided in four groups: sham group (n=4), sham group treated with 5-FC only (n=4), sham group with injection of MVA-FCU1 vector only (n=4), therapy group administered with MVA-FCU1 vector and 5-FC (n=4). Measurements of tumor volumes were obtained after manual segmentation of T1- and T2-weighted images. RESULTS: Intra-observer and inter-observer tumor volume measurements show no significant differences. No differences were found between T1 and T2 volume tumor doubling times between the three sham groups. A significant statistical difference (p<0.05) in T1 and T2 volume tumor doubling times between the three sham groups and the animals treated with the intratumoral injection of MVA-FCU1 vector in combination with 2 weeks per os 5-FC administration was demonstrated. CONCLUSION: Preclinical low field MRI was able to monitor efficacy of suicide gene therapy in delaying the tumor growth in an in vivo mouse model of orthotopic glioblastoma.

Image-guided radio-frequency gain calibration for high-field MRI.

High-field (≥ 3T) MRI provides a means to increase the signal-to-noise ratio, due to its higher tissue magnetization compared with 1.5T. However, both the static magnetic field (B(0)) and the transmit radio-frequency (RF) field (B 1+) inhomogeneities are comparatively higher at higher field strengths than those at 1.5T. These challenging factors at high-field strengths make it more difficult to accurately calibrate the transmit RF gain using standard RF calibration procedures. An image-based RF calibration procedure was therefore developed, in order to accurately calibrate the transmit RF gain within a specific region-of-interest (ROI). Using a turbo fast low-angle shot (TurboFLASH) pulse sequence with centric k-space reordering, a series of 'saturation-no-recovery' images was acquired by varying the flip angle of the preconditioning pulse. In the resulting images, the signal null occurs in regions where the flip angle of the preconditioning pulse is 90°. For a given ROI, the mean signal can be plotted as a function of the nominal flip angle, and the resulting curve can be used to quantitatively identify the signal null. This image-guided RF calibration procedure was evaluated through phantom and volunteer imaging experiments at 3T and 7T. The image-guided RF calibration results in vitro were consistent with standard B(0) and B 1+ maps. The standard automated RF calibration procedure produced approximately 20% and 15-30% relative error in the transmit RF gain in the left kidney at 3T and brain at 7T, respectively. For initial application, a T(2) mapping pulse sequence was applied at 7T. The T(2) measurements in the thalamus at 7T were 60.6 ms and 48.2 ms using the standard and image-guided RF calibration procedures, respectively. This rapid, image-guided RF calibration procedure can be used to optimally calibrate the flip angle for a given ROI and thus minimize measurement errors for quantitative MRI and MR spectroscopy.

In vivo peritoneal surface area measurement in rats by micro-computed tomography (microCT).

Peritoneal dialysis (PD) uses the dynamic dialysis properties of the peritoneal membrane. The fraction of the anatomic peritoneal surface area (PSA) recruited is of importance for maximizing exchanges and is potentially impacted by parameters such as fill volume. We describe an in vivo assessment of the contact surface area by micro-computed tomography (microCT) using an iodinated contrast medium added to the PD fluid, a contrast agent presumed without surfactant property. In the isotropic volume (reconstructed voxel size 186 microm x 186 microm x 186 microm), the iodinated PD fluid is automatically selected, thanks to its contrast difference with soft tissues, and its surface area is computed. The method was first tested on phantoms showing the ability to select the PD fluid volume and to measure its surface area. In vivo experiments in rat consisted of microCT acquisition of rat abdomen directly after intraperitoneal administration (10 mL/100 g rat body weight) of a dialysis fluid containing 10% by volume iodinated contrast agent. Fluorescein isothiocyanate albumin was used as dilution marker. We found a strong linear relationship (R(2) = 0.98) between recruited PSA (cm(2)) and rat weight (g) in the range of 235 to 435 g: recruited PSA = (1.61 weight + 40.5) cm(2). Applying microCT with a fill volume of 10 mL/100 g rat body weight, the in vivo measured PSA was in the order of magnitude of the ex vivo anatomic PSA as determined by Kuzlan's formula, considered in most instances as the maximal surface area that can be recruited by PD fluid. This new methodology was the first to give an in vivo high-resolution isotropic three-dimensional (3-D) determination of the PSA in contact with dialysate. Its sensitivity allows us to take into account the recruitment of fine 3-D structures of the PSA membrane that were not accessible to previous 2-D-based imaging methodologies. Its in vivo application also integrates the physiological natural tensile stress of tissues.

Multiple-contrast X-ray micro-CT visualization of colon malformations and tumours in situ in living mice.

The development of new therapeutic approaches against colorectal cancer requires preclinical studies in mice. In vivo imaging could greatly facilitate these trials, but the small size of the animals is a major limitation for the direct visualization of intestinal tissue. Here we report a method of in vivo imaging of the mouse intestine based on X-ray micro-computed tomography using multiple contrast agents. This method was validated in the model of non-cancerous polyp-like heteroplasia that spontaneously develops in the caecum area of Cdx2+/- mutant mice and in the model of colon adenocarcinoma induced by administration of the chemical carcinogen azoxymethane. As a simple and non-invasive method, multiple-contrast X-ray micro-computed tomography is appropriate for pre-clinical studies of intestinal diseases in living mice.