Chrit Moonen

Magnetic resonance temperature imaging for guidance of thermotherapy.

Continuous thermometry during a hyperthermic procedure may help to correct for local differences in heat conduction and energy absorption, and thus allow optimization of the thermal therapy. Noninvasive, three‐dimensional mapping of temperature changes is feasible with magnetic resonance (MR) and may be based on the relaxation time T1, the diffusion coefficient (D), or proton resonance frequency (PRF) of tissue water. The use of temperature‐sensitive contrast agents and proton spectroscopic imaging can provide absolute temperature measurements. The principles and performance of these methods are reviewed in this paper. The excellent linearity and near‐independence with respect to tissue type, together with good temperature sensitivity, make PRF‐based temperature MRI the preferred choice for many applications at mid to high field strength (≥ 1 T). The PRF methods employ radiofrequency spoiled gradient‐echo imaging methods. A standard deviation of less than 1°C, for a temporal resolution below 1 second and a spatial resolution of about 2 mm, is feasible for a single slice for immobile tissues. Corrections should be made for temperature‐induced susceptibility effects in the PRF method. If spin‐echo methods are preferred, for example when field homogeneity is poor due to small ferromagnetic parts in the needle, the D‐ and T1‐based methods may give better results. The sensitivity of the D method is higher that that of the T1 methods provided that motion artifacts are avoided and the trace of D is evaluated. Fat suppression is necessary for most tissues when T1, D, or PRF methods are employed. The latter three methods require excellent registration to correct for displacements between scans. J. Magn. Reson. Imaging 2000;12:525–533.

Functional Magnetic Resonance Imaging Brain Mapping in Psychiatry: Methodological Issues Illustrated in a Study of Working Memory in Schizophrenia

Functional magnetic resonance imaging (fMRI) is a potential paradigm shift in psychiatric neuroimaging. The technique provides individual, rather than group-averaged, functional neuroimaging data, but subtle methodological confounds represent unique challenges for psychiatric research. As an exemplar of the unique potential and problems of fMRI, we present a study of 10 inpatients with schizophrenia and 10 controls performing a novel “n back” working memory (WM) task. We emphasize two key design steps: (1) the use of an internal activation standard (i.e., a physiological control region) to address activation validity, and (2) the assessment of signal stability to control for “activation” artifacts arising from unequal signal variance across groups. In the initial analysis, all but one of the patients failed to activate dorsolateral prefrontal cortex (DLPFC) during the working memory task. However, some patients (and one control) also tended to show sparse control region activation in spite of normal motor performance, a result that raises doubts about the validity of the initial analysis and concerns about unequal subject motion. Subjects were then matched for signal variance (voxel stability), producing a subset of six patients and six controls. In this comparison, the internal activation standard (i.e., motor activation) was similar in both groups, and five of six patients, including two whom were neuroleptic-naive, failed to activate DLPFC. In addition, a tendency for overactivation of parietal cortex was seen. These results illustrate some of the promise and pitfalls of fMRI. Although fMRI generates individual brain maps, a specialized survey of the data is necessary to avoid spurious or unreliable findings, related to artifacts such as motion, which are likely to be frequent in psychiatric patients.

Volumetric HIFU ablation under 3D guidance of rapid MRI thermometry.

A volumetric sonication method is proposed that produces volume ablations by steering the focal point along a predetermined trajectory consisting of multiple concentric outward-moving circles. This method was tested in vivo on pig thigh muscle (32 ablations in nine animals). Trajectory diameters were 4, 12, and 16 mm with sonication duration depending on the trajectory size and ranging from 20 to 73 s. Despite the larger trajectories requiring more energy to reach necrosis within the desired volume, the ablated volume per unit applied energy increased with trajectory size, indicating improved treatment efficiency for larger trajectories. The higher amounts of energy required for the larger trajectories also increased the risk of off-focus heating, especially along the beam axis in the near field. To avoid related adverse effects, rapid volumetric multiplane MR thermometry was introduced for simultaneous monitoring of the temperature and thermal dose evolution along the beam axis and in the near field, as well as in the target region with a total coverage of six slices acquired every 3 s. An excellent correlation was observed between the thermal dose and both the nonperfused (R=0.929 for the diameter and R=0.964 for the length) and oedematous (R=0.913 for the diameter and R=0.939 for the length) volumes as seen in contrast-enhanced T1-weighted difference images and T2-weighted postsonication images, respectively. Histology confirmed the presence of a homogeneous necrosis inside the heated volumes. These results show that volumetric high-intensity focused ultrasound (HIFU) sonication allows for efficiently creating large thermal lesions while reducing treatment duration and also that the rapid multiplane MR thermometry improves the safety of the therapeutic procedure by monitoring temperature evolution both inside as well as outside the targeted volume.

Diffusion tensor MRI of the human kidney

This study characterizes the diffusion anisotropy of the human kidney using a diffusion‐weighted, single‐shot echo planar imaging (EPI) sequence in order to access the full apparent diffusion tensor (ADT) within one breathhold. The fractional anisotropy (FA) of the cortex and the medulla were found to be 0.22 ± 0.12 and 0.39 ± 0.11, respectively (N = 10), which emphasizes the need for rotationally invariant diffusion measurements for clinical applications. Additional limitations for clinical diffusion imaging on the kidney are the strong susceptibility variations within the abdomen that restrict the use of imaging techniques employing long echo trains, and the severe motion sensitivity that limits the available imaging time to one breath‐hold. To overcome these problems an isotropic, diffusion‐weighted, segmented EPI protocol that facilitates the acquisition of high‐resolution diffusion‐weighted images within a single breath‐hold was implemented. Using this method, the apparent diffusion coefficient (ADC) of the cortex and medulla were found to be 2.89 ± 0.28 · 10−9 m2/s and 2.18 ± 0.36 · 10−9 m2/s (N = 10). J. Magn. Reson. Imaging 2001;14:42–49.

Real‐time adaptive methods for treatment of mobile organs by MRI‐controlled high‐intensity focused ultrasound

Focused ultrasound (US) is a unique and noninvasive technique for local deposition of thermal energy deep inside the body. MRI guidance offers the additional benefits of excellent target visualization and continuous temperature mapping. However, treating a moving target poses severe problems because 1) motion‐related thermometry artifacts must be corrected, 2) the US focal point must be relocated according to the target displacement. In this paper a complete MRI‐compatible, high‐intensity focused US (HIFU) system is described together with adaptive methods that allow continuous MR thermometry and therapeutic US with real‐time tracking of a moving target, online motion correction of the thermometry maps, and regional temperature control based on the proportional, integral, and derivative method. The hardware is based on a 256‐element phased‐array transducer with rapid electronic displacement of the focal point. The exact location of the target during US firing is anticipated using automatic analysis of periodic motions. The methods were tested with moving phantoms undergoing either rigid body or elastic periodical motions. The results show accurate tracking of the focal point. Focal and regional temperature control is demonstrated with a performance similar to that obtained with stationary phantoms. Magn Reson Med 57:319–330, 2007.

Understanding ultrasound induced sonoporation: Definitions and underlying mechanisms ☆

In the past two decades, research has underlined the potential of ultrasound and microbubbles to enhance drug delivery. However, there is less consensus on the biophysical and biological mechanisms leading to this enhanced delivery. Sonoporation, i.e. the formation of temporary pores in the cell membrane, as well as enhanced endocytosis is reported. Because of the variety of ultrasound settings used and corresponding microbubble behavior, a clear overview is missing. Therefore, in this review, the mechanisms contributing to sonoporation are categorized according to three ultrasound settings: i) low intensity ultrasound leading to stable cavitation of microbubbles, ii) high intensity ultrasound leading to inertial cavitation with microbubble collapse, and iii) ultrasound application in the absence of microbubbles. Using low intensity ultrasound, the endocytotic uptake of several drugs could be stimulated, while short but intense ultrasound pulses can be applied to induce pore formation and the direct cytoplasmic uptake of drugs. Ultrasound intensities may be adapted to create pore sizes correlating with drug size. Small molecules are able to diffuse passively through small pores created by low intensity ultrasound treatment. However, delivery of larger drugs such as nanoparticles and gene complexes, will require higher ultrasound intensities in order to allow direct cytoplasmic entry.

Local hyperthermia with MR-guided focused ultrasound: Spiral trajectory of the focal point optimized for temperature uniformity in the target region

The objective of hyperthermia treatment is to deliver a similar therapeutic thermal dose throughout the target volume within a minimum amount of time. We describe a noninvasive approach to this goal based on magnetic resonance imaging (MRI)‐guided focused ultrasound (FUS) with a spherical transducer that can be moved along two directions inside the bed of a clinical MR imager and that has an adjustable focal length in the third dimension. Absorption of FUS gives rise to a highly localized thermal buildup, which then spreads by heat diffusion and blood perfusion. A uniform temperature within a large target volume can be obtained using a double spiral trajectory of the transducer focal point together with constant and maximum FUS power. Differences between the real and target temperatures during the first spiral are evaluated in real time with temperature MRI and corrected for during the second spiral trajectory employing FUS focal point velocity modulation. Once a uniform temperature distribution is reached within the entire volume, FUS heating is applied only at the regions boundaries to maintain the raised temperature levels. Heat conduction, together with the design and timing of the trajectories, therefore ensures a similar thermal dose for the entire target region. Good agreement is obtained between theory and experimental results in vitro on gel phantoms, ex vivo on meat samples, and in vivo on rabbit thigh muscle. Edema in muscle was visible 1 hour after hyperthermia as a spatially uniform rise of the signal intensity in T2‐weighted images. J. Magn. Reson. Imaging 2000;12:571–583.

Magnetic resonance temperature imaging.

Continuous, real-time, 3D temperature mapping during a hyperthermic procedure may provide (i) enhanced safety by visualizing temperature maps in and around the treated region, (ii) improved efficiency by adapting local energy deposition with feedback coupling algorithms and (iii) therapy end-points based on the accumulated thermal dose. Non-invasive mapping of temperature changes can be achieved with MRI and may be based on temperature dependent MRI parameters. The excellent linearity of the temperature dependency of the proton resonance frequency (PRF) and its near-independence with respect to tissue type make the PRF-based methods the preferred choice for many applications, in particular at mid- to-high field strength (≥0.5 T). The PRF methods employ RF-spoiled gradient echo imaging methods and incorporate fat suppression techniques for most organs. A standard deviation of less than 1°C, for a temporal resolution below 1 s and a spatial resolution of ∼2 mm is feasible for immobile tissues. Special attention is paid to methods for reducing artifacts in MR temperature mapping caused by intra-scan and inter-scan motion and motion and temperature-induced susceptibility effects in mobile tissues. Real-time image processing and visualization techniques, together with accelerated MRI acquisition techniques, are described because of their potential for therapy guidance.

Diffusion tensor MRI of the spinal cord

Apparent diffusion tensor (ADT) measurements on the spinal cord using a pulsed‐field‐gradient (PFG) multi‐shot echo‐planar imaging (EPI) sequence are presented. In a study of 10 healthy volunteers, the obtained rotationally invariant anisotropy information is compared to the results obtained by the rotationally dependent methods. The water diffusivity in the direction parallel to the fibers was found to be almost 2.5 times higher than the average diffusivity in directions perpendicular to the fibers and showed cylindrically symmetric anisotropy characteristics. The influence of partial volume effects and the point spread function on the measured results was evaluated, and it was the concluded that a resolution of 1 mm in the read and phase directions is required to obtain unbiased values. Possible clinical implications were demonstrated by investigating the diffusion characteristics of 10 patients suffering from narrowing of the cervical canal. The changes in the diffusion characteristics were found to be large enough to allow a robust detection of diffusion changes in the spine, even in cases in which conventional T2 and T1 weighted images were unable to detect any lesion. Magn Reson Med 44:884–892, 2000.

Hyperthermia by MR-guided focused ultrasound: Accurate temperature control based on fast MRI and a physical model of local energy deposition and heat conduction

Temperature regulation in MR‐guided focused ultrasound requires rapid MR temperature mapping and automatic feedback control of the ultrasound output. Here, a regulation method is proposed based on a physical model of local energy deposition and heat conduction. The real‐time evaluation of local temperature gradients from temperature maps is an essential element of the control system. Each time a new image is available, ultrasound power is adjusted on‐the‐fly in order to obtain the desired evolution of the focal point temperature. In vitro and in vivo performance indicated fast and accurate control of temperature and a large tolerance of errors in initial estimates of ultrasound absorption and heat conduction. When using correct estimates for the physical parameters of the model, focal point temperature was controlled within the measurement noise limit. Initial errors in absorption and diffusion parameters are compensated for exponentially with a user‐defined response time, which is suggested to be on the order of 10 sec. Magn Reson Med 43:342–347, 2000.