Sara M. Sprinkhuizen

Three-dimensional spatial and temporal temperature control with MR thermometry-guided focused ultrasound (MRgHIFU)

High‐intensity focused ultrasound (HIFU) is an efficient noninvasive technique for local heating. Using MRI thermal maps, a proportional, integral, and derivative (PID) automatic temperature control was previously applied at the focal point, or at several points within a plane perpendicular to the beam axis using a multispiral focal point trajectory. This study presents a flexible and rapid method to extend the spatial PID temperature control to three dimensions during each MR dynamic. The temperature in the complete volume is regulated by taking into account the overlap effect of nearby sonication points, which tends to enlarge the heated area along the beam axis. Volumetric temperature control in vitro in gel and in vivo in rabbit leg muscle was shown to provide temperature control with a precision close to that of the temperature MRI measurements. The proposed temperature control ensures heating throughout the volume of interest of up to 1 ml composed of 287 voxels with 95% of the energy deposited within its boundaries and reducing the typical average temperature overshoot to 1°C. Magn Reson Med, 2009.

Temperature-induced tissue susceptibility changes lead to significant temperature errors in PRFS-based MR thermometry during thermal interventions.

Proton resonance frequency shift‐based MR thermometry (MRT) is hampered by temporal magnetic field changes. Temporal changes in the magnetic susceptibility distribution lead to nonlocal field changes and are, therefore, a possible source of errors. The magnetic volume susceptibility of tissue is temperature dependent. For water‐like tissues, this dependency is in the order of 0.002 ppm/°C. For fat, it is in the same order of magnitude as the temperature dependence of the proton electron screening constant of water (0.01 ppm/°C). For this reason, proton resonance frequency shift‐based MR thermometry in fatty tissues, like the human breast, is expected to be prone to errors. We aimed to quantify the influence of the temperature dependence of the susceptibility on proton resonance frequency shift‐based MR thermometry. Heating experiments were performed in a controlled phantom set‐up to show the impact of temperature‐induced susceptibility changes on actual proton resonance frequency shift‐based temperature maps. To study the implications for a clinical case, simulations were performed in a 3D breast model. Temperature errors were quantified by computation of magnetic field changes in the glandular tissue, resulting from susceptibility changes in a thermally heated region. The results of the experiments and simulations showed that the temperature‐induced susceptibility changes of water and fat lead to significant errors in proton resonance frequency shift‐based MR thermometry. Magn Reson Med, 2010.

Do respiration and cardiac motion induce magnetic field fluctuations in the breast and are there implications for MR thermometry

To assess the distribution of respiration and cardiac motion‐induced field fluctuations in the breast and to evaluate the implications of such fluctuations for proton resonance frequency shift (PRFS) MR thermometry in the breast.

Aortic Pulsatile Distention in Young Healthy Volunteers is Asymmetric : Analysis with ECG-gated MRI

OBJECTIVE Knowledge of aortic shape changes throughout the cardiac cycle can offer improved understanding of vascular pathophysiology and may have crucial impact on stentgraft design and EVAR durability. To understand underlying mechanisms of dynamic changes in aortic aneurysm (neck) morphology, the undiseased aorta has to be studied first. Objective is to visualize and characterize dynamic aortic shape changes in young healthy volunteers. MATERIALS AND METHODS Fifteen healthy volunteers (7 male, median age 24 year, range 18-28) were scanned using ECG-gated balanced gradient-echo MRI, with 16 reconstructed cardiac phases. Transverse scans were made perpendicular to the aorta: (A) above the aortic bifurcation, (B) infrarenal, (C) juxtarenal, (D) suprarenal and (E) above the celiac trunk. After aortic lumen segmentation, radial changes during the cardiac cycle were measured, from the center of mass, over 360 degrees, and plotted. An ellipse was fitted over the distention plots, yielding the direction (AP:0 degrees, Right: -90 degrees, Left: 90 degrees ) and magnitude of radius change over the major and minor axis. RESULTS Asymmetric distention was observed, with a variable rate per patient and level. Radius changes decreased from the proximal to distal aorta. Radius changes over the major axis ranged from 14% to 41%. At level A mean change in radius over the minor versus major axis was 1.4+/-0.2mm (17%) versus 1.6+/-0.2mm (20%), respectively. At B 1.7+/-0.4mm (22%) versus 2.0+/-0.4mm (25%), at C 1.7+/-0.4mm (22%) versus 2.2+/-0.4mm (27%) at D 2.0+/-0.4mm (25%) versus 2.4+/-0.5mm (30%) and at E 2.2+/-0.3mm (27%) versus 2.6+/-0.3mm (32%). Mean orientation of the major axis was (A) 0.8+/-23.3 degrees , (B) 1.8+/-31.3 degrees , (C) 14.0+/-15.5 degrees , (D) -28.8+/-48.0 degrees and (E) 18.4+/-22.2 degrees. CONCLUSIONS Aortic pulsatile distention in young healthy volunteers is asymmetric, with up to 41% radius change in the descending aorta. This study offers a frame of reference for dynamic imaging studies in patients with aortic pathology and provides a valuable non-invasive tool for future research into aortic distention, development and localization of vascular pathology.

Absolute MR thermometry using time-domain analysis of multi-gradient-echo magnitude images.

MRI allows for absolute temperature measurements in substances containing two spectral resonances of which the frequency difference Δf(T) is related to absolute temperature. This frequency difference can be extracted from spectroscopic data. An image‐based MR technique that allows for the acquisition of spectroscopic data at high temporal and spatial resolution is the multi‐gradient‐echo sequence. In this work, the application of the multi‐gradient‐echo sequence for MR thermometry purposes was further developed. We investigated the possibility of postprocessing the multi‐gradient‐echo data into absolute temperature maps, using time‐domain analysis of the magnitude of the multi‐gradient‐echo signals. In this approach, instead of an indirect computation of Δf(T) from separately found frequencies, Δf(T) is a direct output parameter. In vitro experiments were performed to provide proof of concept for retrieving absolute temperature maps from the time‐domain analysis of multi‐gradient‐echo magnitude images. It is shown that this technique is insensitive to both field drift and local field disturbances. Furthermore, ex vivo bone marrow experiments were performed, using the fat resonance as a reference for absolute temperature mapping. It is shown that the postprocessing based on the magnitude signal in the time domain allows for the determination of Δf(T) in bone marrow. Magn Reson Med 64:239–248, 2010.

Registration of 2D x-ray images to 3D MRI by generating pseudo-CT data

Spatial and soft tissue information provided by magnetic resonance imaging can be very valuable during image-guided procedures, where usually only real-time two-dimensional (2D) x-ray images are available. Registration of 2D x-ray images to three-dimensional (3D) magnetic resonance imaging (MRI) data, acquired prior to the procedure, can provide optimal information to guide the procedure. However, registering x-ray images to MRI data is not a trivial task because of their fundamental difference in tissue contrast. This paper presents a technique that generates pseudo-computed tomography (CT) data from multi-spectral MRI acquisitions which is sufficiently similar to real CT data to enable registration of x-ray to MRI with comparable accuracy as registration of x-ray to CT. The method is based on a k-nearest-neighbors (kNN)-regression strategy which labels voxels of MRI data with CT Hounsfield Units. The regression method uses multi-spectral MRI intensities and intensity gradients as features to discriminate between various tissue types. The efficacy of using pseudo-CT data for registration of x-ray to MRI was tested on ex vivo animal data. 2D-3D registration experiments using CT and pseudo-CT data of multiple subjects were performed with a commonly used 2D-3D registration algorithm. On average, the median target registration error for registration of two x-ray images to MRI data was approximately 1 mm larger than for x-ray to CT registration. The authors have shown that pseudo-CT data generated from multi-spectral MRI facilitate registration of MRI to x-ray images. From the experiments it could be concluded that the accuracy achieved was comparable to that of registering x-ray images to CT data.

Absolute MR thermometry using nanocarriers

Accurate time-resolved temperature mapping is crucial for the safe use of hyperthermia-mediated drug delivery. We here propose a magnetic resonance imaging temperature mapping method in which drug delivery systems serve not only to improve tumor targeting, but also as an accurate and absolute nano-thermometer. This method is based on the temperature-dependent chemical shift difference between water protons and the protons in different groups of drug delivery systems. We show that the chemical shift of the protons in the ethylene oxide group in polyethylene glycol (PEG) is temperature-independent, whereas the proton resonance of water decreases with increasing temperature. The frequency difference between both resonances is linear and does not depend on pH and physiological salt conditions. In addition, we show that the proton resonance of the methyl group in N-(2-hydroxypropyl)-methacrylamide (HPMA) is temperature-independent. Therefore, PEGylated liposomes, polymeric mPEG-b-pHPMAm-Lac2 micelles and HPMA copolymers can provide a temperature-independent reference frequency for absolute magnetic resonance (MR) thermometry. Subsequently, we show that multigradient echo MR imaging with PEGylated liposomes in situ allows accurate, time-resolved temperature mapping. In conclusion, nanocarrier materials may serve as highly versatile tools for tumor-targeted drug delivery, acting not only as hyperthermia-responsive drug delivery systems, but also as accurate and precise nano-thermometers.

Temperature Dependence of the Susceptibility of Fat Leads to Significant Temperature Errors in PRFS‐based MR Thermometry

Proton resonance frequency shift (PRFS)‐based MR thermometry is hampered by temporal field changes. Temporal changes in the susceptibility distribution lead to field changes and are therefore a possible source of errors. The susceptibility of fat, χfat, is temperature dependent, in the same order of magnitude as the temperature dependence of the chemical shift of water (0.01 ppm/° C). PRFS‐based temperature measurements may therefore be corrupted by non‐local field effects due to temperature induced susceptibility changes in fatty tissue. We performed simulations to quantify the influence of dχfat/dT on PRFS‐based MR temperature maps during thermal interventions in the breast. Susceptibility distributions were calculated for a 3D breast model without and with a stationary Gaussian temperature distribution and a maximum temperature of 57° C. Subsequently, the magnetic field was calculated in Fourier‐domain from these susceptibility distributions. Changes in the magnetic field distribution were quantified b...