[en] Developing a method of separating intravascular contrast agent concentration to measure the arterial input function (AIF) in dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) of tumours, and validating its performance in phantom and in vivo experiments. A tissue-mimicking phantom was constructed to model leaky tumour vasculature and DCE-MR images of this phantom were acquired. An in vivo study was performed using tumour-bearing rabbits. Co-registered DCE-MRI and contrast-enhanced ultrasound (CEUS) images were acquired. An independent component analysis (ICA)-based method was developed to separate the intravascular component from DCE-MRI. Results were validated by comparing the time-intensity curves with the actual phantom and in vivo curves. Phantom study: the AIF extracted using ICA correlated well with the true intravascular curve. In vivo study: the AIFs extracted from DCE-MRI using ICA were very close to the true AIF. Intravascular component images were very similar to the CEUS images. The contrast onset times and initial wash-in slope of the ICA-derived AIF showed good agreement with the CEUS curves. ICA has the potential to separate the intravascular component from DCE-MRI. This could eliminate the requirement for contrast medium uptake measurements in a major artery and potentially result in more accurate pharmacokinetic parameters. (orig.)

[en] MRI-controlled transurethral ultrasound therapy uses a linear array of transducer elements and active temperature feedback to create volumes of thermal coagulation shaped to predefined prostate geometries in 3D. The specific aims of this work were to demonstrate the accuracy and repeatability of producing large volumes of thermal coagulation (>10 cc) that conform to 3D human prostate shapes in a tissue-mimicking gel phantom, and to evaluate quantitatively the accuracy with which numerical simulations predict these 3D heating volumes under carefully controlled conditions. Eleven conformal 3D experiments were performed in a tissue-mimicking phantom within a 1.5T MR imager to obtain non-invasive temperature measurements during heating. Temperature feedback was used to control the rotation rate and ultrasound power of transurethral devices with up to five 3.5 x 5 mm active transducer elements. Heating patterns shaped to human prostate geometries were generated using devices operating at 4.7 or 8.0 MHz with surface acoustic intensities of up to 10 W cm^-2. Simulations were informed by transducer surface velocity measurements acquired with a scanning laser vibrometer enabling improved calculations of the acoustic pressure distribution in a gel phantom. Temperature dynamics were determined according to a FDTD solution to Pennes' BHTE. The 3D heating patterns produced in vitro were shaped very accurately to the prostate target volumes, within the spatial resolution of the MRI thermometry images. The volume of the treatment difference falling outside ±1 mm of the target boundary was, on average, 0.21 cc or 1.5% of the prostate volume. The numerical simulations predicted the extent and shape of the coagulation boundary produced in gel to within (mean ± stdev [min, max]): 0.5 ± 0.4 [-1.0, 2.1] and -0.05 ± 0.4 [-1.2, 1.4] mm for the treatments at 4.7 and 8.0 MHz, respectively. The temperatures across all MRI thermometry images were predicted within -0.3 ± 1.6 ⁰C and 0.1 ± 0.6 ⁰C, inside and outside the prostate respectively, and the treatment time to within 6.8 min. The simulations also showed excellent agreement in regions of sharp temperature gradients near the transurethral and endorectal cooling devices. Conformal 3D volumes of thermal coagulation can be precisely matched to prostate shapes with transurethral ultrasound devices and active MRI temperature feedback. The accuracy of numerical simulations for MRI-controlled transurethral ultrasound prostate therapy was validated experimentally, reinforcing their utility as an effective treatment planning tool.

[en] A tissue-mimicking phantom material has been developed for use with thermal therapy devices and techniques. This material has magnetic resonance properties (primarily T₂) which change drastically upon thermal coagulation, enabling its use for device characterization and treatment verification using simple T₂-weighted imaging techniques. The coagulation temperature of the phantom can be changed from 50-60 deg. C by adjusting the pH from 4.3 to 4.7. The energy absorption properties can be adjusted to match the acoustical and optical properties of tissues. T₂ relaxation measurements are provided as a function of temperature, along with T₂-weighted MR images to illustrate the visualization of heating patterns. A complete recipe for fabricating phantoms is provided

[en] Piezoceramic actuators are capable of precise positioning with high force, but suffer from limited displacement range, which has hindered their application in the field of magnetic resonance elastography (MRE). The objective of this study was to investigate the feasibility of using a mechanical amplifier in combination with a piezoceramic actuator for the application of endorectal prostate MRE. A five-bar symmetric structure was designed in ANSYS^® and manufactured out of brass. Laser vibrometer measurements were used to characterize the amplitude of the CMA actuator while attached to masses in the 0–325 g range and over operating frequencies of 90–500 Hz. The response of the CMA was investigated while mechanically coupled to a balloon type endorectal coil. The resonant frequency of the prototype CMA actuator was predicted within 10% error using ANSYS simulations. The amplification ratio of the CMA actuator was measured to be 10 with the laser vibrometer and 7.6 ± 1.7 (max: 9.2, min: 6.5) using MRE, at a vibration frequency of 200 Hz. Laser vibrometer data also showed that the CMA actuator’s performance did not change whether it was connected to an empty or inflated endorectal. The feasibility of performing endorectal prostate MRE with a CMA actuator was successfully demonstrated in a human volunteer. (technical note)

[en] Imaging of the microvasculature is often performed using contrast agents in combination with either ultrasound (US) or magnetic resonance (MR) imaging. Contrast agents are used to enhance medical imaging by highlighting microvascular properties and function. Dynamic signal changes arising from the passage of contrast agents through the microvasculature can be used to characterize different pathologies; however, comparisons across modalities are difficult due to differences in the interactions of contrast agents with the microvasculature. Better knowledge of the relationship of contrast enhancement patterns with both modalities could enable better characterization of tissue microvasculature. We developed a co-registration platform for multi-modal US and MR imaging using clinical imaging systems in order to study the relationship between US and MR contrast enhancement. A preliminary validation study was performed in phantoms to determine the registration accuracy of the platform. In phantoms, the in-plane registration accuracy was measured to be 0.2 ± 0.2 and 0.3 ± 0.2 mm, in the lateral and axial directions, respectively. The out-of-plane registration accuracy was estimated to be 0.5 mm ±0.1. Co-registered US and MR imaging was performed in a rabbit model to evaluate contrast kinetics in different tissue types after bolus injections of US and MR contrast agents. The arrival time of the contrast agent in the plane of imaging was relatively similar for both modalities. We studied three different tissue types: muscle, large vessels and fat. In US, the temporal kinetics of signal enhancement were not strongly dependent on tissue type. In MR, however, due to the different amounts of agent extravasation in each tissue type, tissue-specific contrast kinetics were observed. This study demonstrates the feasibility of performing in vivo co-registered contrast US and MR imaging to study the relationships of the enhancement patterns with each modality.

[en] The objective of this study was to develop a real-time method for controlling focused ultrasound surgery using ultrasound imaging. The approach uses measurements of localized harmonic motion (LHM) in order to perform controlled FUS exposures by detecting changes in the elastic properties of tissues during coagulation. Methods: Nine New Zealand rabbits with VX2 tumors implanted in the thigh were used for this study. LHM was generated within the tumors by periodic induction of radiation force using a FUS transducer (80-mm focal length, 100-mm diameter, 20-mm central hole, 1.485-MHz). Tissue motion was tracked by collecting and cross-correlating RF signals during the motion using a separate diagnostic transducer (3-kHz PRF, 5-MHz). After locating the tumor in MR images, a series of sonications were performed to treat the tumors using a reduction in LHM amplitude to control the exposure. Results: LHM was successfully used to control the sonications. A LHM amplitude threshold value was determined at which changes were considered significant and then the exposure was started and stopped when the LHM amplitude dropped below the threshold. The appearance of a lesion was then verified by MRI. The feasibility of LHM measurements to control FUS exposure was validated.

[en] Transurethral thermal therapy offers a minimally invasive alternative for the treatment of prostate diseases including benign prostate hyperplasia (BPH) and prostate cancer. Accurate heating of a targeted region of the gland can be achieved through the use of a rotating directional heating source incorporating planar ultrasound transducers, and the implementation of active temperature feedback along the beam direction during heating provided by magnetic resonance (MR) thermometry. The performance of this control method with practical spatial, temporal, and temperature resolution (such as angular alignment, spatial resolution, update rate for temperature feedback (imaging time), and the presence of noise) for thermal feedback using a clinical 1.5 T MR scanner was investigated in simulations. As expected, the control algorithm was most sensitive to the presence of noise, with noticeable degradation in its performance above ±2 deg. C of temperature uncertainty. With respect to temporal resolution, acceptable performance was achieved at update rates of 5s or faster. The control algorithm was relatively insensitive to reduced spatial resolution due to the broad nature of the heating pattern produced by the heating applicator, this provides an opportunity to improve signal-to-noise ratio (SNR). The overall simulation results confirm that existing clinical 1.5T MR imagers are capable of providing adequate temperature feedback for transurethral thermal therapy without special pulse sequences or enhanced imaging hardware

[en] The ability to control the shape of thermal coagulation was investigated for various interstitial heating applicators incorporating planar transducers and device rotation. Magnetic-resonance-compatible interstitial ultrasound applicators were constructed and the effects of ultrasound power, frequency, scan rate and heating time on lesion radius were studied in heating experiments in excised liver tissue. Continuous thermal lesions were generated by scanning heating applicators over a 180 deg angular sector. The region of thermal coagulation was restricted to the prescribed sector. Lesion radius increased with acoustic power and heating time and decreased with increasing frequency. The relationship between the temperature distribution generated by the applicator and the resulting thermal lesion was assessed with MRI. Analysis of MR temperature maps revealed that the temperature distribution could be measured accurately within 2 mm from the surface of the applicator, and the boundary of thermal coagulation was defined by a temperature of 54±2 deg. C. Calculations of temperature distributions indicated that slower scan rates can overcome the tendency of perfusion to reduce the radius of thermal lesion. This applicator design and delivery strategy make conformal interstitial heating possible. (author)

[en] High cure rates for testicular cancer have prompted interest in organ-sparing surgery for patients with bilateral disease or single testis. Focused ultrasound (FUS) ablation could offer a noninvasive approach to organ-sparing surgery. The objective of this study was to determine the feasibility of using MR thermometry to guide organ-sparing focused ultrasound surgery in the testis. The testes of anesthetized rabbits were sonicated in several discrete locations using a single-element focused transducer operating at 2.787MHz. Focal heating was visualized with MR thermometry, using a measured PRF thermal coefficient of -0.0089±0.0003 ppm/ deg. C. Sonications at 3.5-14 acoustic watts applied for 30 seconds produced maximum temperature elevations of 10-80 deg. C, with coagulation verified by histology. Coagulation of precise volumes in the testicle is feasible with MRI-guided focused ultrasound. Variability in peak temperature for given sonication parameters suggests the need for online temperature feedback control.

[en] Accurate dose delivery in stereotactic partial breast irradiation (S-PBI) is challenging because of the target position uncertainty caused by breast deformation, the target volume changes caused by lumpectomy cavity shrinkage, and the target delineation uncertainty on simulation computed tomography (CT) images caused by poor soft tissue contrast. We have developed a volumetric ultrasound tomography (UST) image guidance system for prone position S-PBI. The system is composed of a novel 3D printed rotation water tank, a patient-specific resin breast immobilization cup, and a 1D array ultrasound transducer. Coronal 2D US images were acquired in 5° increments over a 360° range, and planes were acquired every 2 mm in elevation. A super-compounding technique was used to reconstruct the image volume. The image quality of UST was evaluated with a BB-1 breast phantom and BioZorb surgical marker, and the results revealed that UST offered better soft tissue contrast than CT and similar image quality to MR. In the evaluated plane, the size and location of five embedded objects were measured and compared to MR, which is considered as the ground truth. Objects’ diameters and the distances between objects in UST differ by approximately 1 to 2 mm from those in MR, which showed that UST offers the image quality required for S-PBI. In future work we will develop a robotic system that will be ultimately implemented in the clinic. (paper)