Associations of osteoprotegerin with coronary artery calcification among women with systemic lupus erythematosus and healthy controls.

Objective We tested the hypothesis that higher circulating levels of osteoprotegerin (OPG) are related to higher levels of coronary artery calcification (CAC) among women with systemic lupus erythematosus (SLE) compared with healthy controls (HCs). Methods Among 611 women in two age- and race-matched SLE case-control studies, OPG was assayed in stored blood samples (HEARTS: plasma, n cases/controls = 122/124, and SOLVABLE: serum, n cases/controls = 185/180) and CAC was measured by electron beam computed tomography. Results In both studies, SLE patients had higher OPG and CAC levels than HCs. Higher OPG was associated with high CAC (>100 vs.100) among SLE, and with any CAC (>0 vs. 0) among HCs. Multivariable-adjusted OR (95% CI) for OPG tertile 3 vs. 1 was 3.58 (1.19, 10.76), p trend = 0.01 for SLE, and 2.28 (1.06, 4.89), p trend = 0.04 for HCs. Associations were attenuated when age-adjusted, but remained significant for HC women aged ≥ 40 and SLE women aged ≥ 50. ROC analyses identified 4.60 pmol/l as the optimal OPG cutpoint for predicting high CAC (>100) among SLE patients with sensitivity = 0.74 and specificity = 0.61, overall, but 0.92 and 0.52, respectively, for SLE patients aged ≥ 50. Conclusion Our cross-sectional results suggest that higher OPG levels are related to higher CAC levels among women with SLE vs. healthy controls.

Thermal dosimetry of a focused ultrasound beam in vivo by magnetic resonance imaging.

Magnetic resonance imaging (MRI) thermometry has been utilized for in vivo evaluation of thermal exposure induced by a focused ultrasound beam. A simulation study of the focused ultrasound beam was conducted to select imaging parameters for reducing the error due to the spatial and temporal averaging of MRI. Temperature imaging based on the proton resonance frequency shift was utilized to obtain the temperature distribution during sonication in the skeletal muscle of eight rabbits. MRI-derived temperature information was then used to calculate the thermal dose distribution induced by the sonication and to estimate the coagulated tissue volume. The tissue changes were also evaluated directly by taking the T2-weighted and the contrast agent enhanced T1-weighted MR images. Errors in the temperature and thermal dose measurements were found to be minimal using the following parameters: slice thickness = 3 mm, voxel dimension = 0.6 mm, and scan time per image = 3.4 s. The estimated dimensions of the coagulated tissue volume were in good agreement with the tissue damages seen on the contrast agent enhanced T1-weighted images. The tissue damage seen on the histology was closely matched to the ones seen on the T2-weighted images. This study showed that MRI thermometry has significant potential for both monitoring the thermal exposure and evaluating the tissue damage. This would allow real-time control of the sonication parameters to optimize clinical treatments.

Calibration of water proton chemical shift with temperature for noninvasive temperature imaging during focused ultrasound surgery.

The present work was performed to calibrate water proton chemical shift change with tissue temperature in vivo to establish a method of quantitative temperature imaging during focused ultrasound surgery. The chemical shift change measured with a phase-mapping method using spoiled gradient-recalled acquisition in steady state (SPGR) (TR = 26 msec, TE = 12.8 msec, matrix = 256 x 128) was calibrated with the corresponding temperature elevation (0-50 degrees C, 32-84 degrees C in absolute temperature) measured with a copper-constantan thermocouple (.05-mm-diameter bare wires) in rabbit skeletal muscle (16 animals) under focused ultrasound exposures (10-100 W radiofrequency [RF] power, 20-second sonication). A linear calibration with a regression coefficient of (-8.76+/-.69) x 10(-3) ppm/degrees C (P < .01 [P, significance level]) was obtained. Temperature distributions during a 20-second sonication were visualized every 3.3 seconds with a 2.3-mm3 spatial resolution and 4 degrees C temperature uncertainty.

Temperature mapping using the water proton chemical shift: a chemical shift selective phase mapping method.

A proton-chemical-shift-based temperature imaging method, called chemical shift selective phase mapping, is proposed. The technique uses frequency-selective suppression to provide frequency selectivity to the phase mapping method. Separate imaging of the phase distributions of the water and nonwater signals reduced the error due to the presence of a nonwater signal in measuring the water proton chemical shift change in two-component samples. Imaging of the phase difference between water and oil yielded an internally referenced water proton chemical shift measurement to visualize the temperature change distribution, which was unaffected by motion-induced susceptibility changes.

Thermal effects of focused ultrasound on the brain: determination with MR imaging.

PURPOSE: To determine the feasibility of the use of temperature-sensitive magnetic resonance (MR) imaging for the detection of local temperature elevations at the focus of a low-power ultrasound beam in the brain. MATERIALS AND METHODS: The brains in 28 rabbits were sonicated at acoustic power levels of 3.5-17.5 W. Four to five different locations were sonicated at different acoustic power levels in each rabbit. MR images were obtained 2 hours, 48 hours, 10 days, and 23 days after the sonications, depending on when the animals were sacrificed. Histologic evaluation of whole brain was performed. RESULTS: Forty of 43 (93%) of the lowest-power (3.5-W) sonications were visible on temperature-sensitive MR images and did not result in any short- or long-term histologic or MR imaging evidence of tissue damage. A contrast-to-noise ratio of approximately 6 and a temperature elevation of 7 degrees-8 degrees C were observed. CONCLUSION: Temperature elevations induced by means of focused ultrasound exposures that do not cause damage in the in vivo rabbit brain can be detected at temperature-sensitive MR imaging.

Temperature monitoring of ultrasonically heated muscle with RARE chemical shift imaging.

The ability to monitor tissue temperature in ultrasonically heated rabbit muscle is demonstrated using a chemical shift imaging approach based on the rapid acquisition with relaxation enhancement (RARE) fast imaging method [Hennig et al., Magn. Reson. Med. 3, 823-833 (1986)] applied in a line scan format. A three echo sequence with a 16 Hz spectral resolution with 64 ms echo readouts and 78 ms echo spacings is shown capable of measuring relevantly small water frequency shifts in phantoms. Applied to the in vivo model of ultrasonically heated rabbit muscle, water resonance frequencies at the ultrasonic focal point were found to be linearly related to temperature with a slope of -0.007 +/- 0.001 ppm/degree C (N = 6 studies). Measurements of the frequency shift in unheated tissue located away from the ultrasonically heated tissue varied by approximately 0.011 ppm over the course of the experiments, leading to an estimated temperature accuracy of +/- 1.6 degrees C in vivo.

Optimization of spoiled gradient-echo phase imaging for in vivo localization of a focused ultrasound beam.

The parameters of a spoiled gradient-echo (SPGR) pulse sequence have been optimized for in vivo localization of a focused ultrasound beam. Temperature elevation was measured by using the proton resonance frequency shift technique, and the phase difference signal-to-noise ratio (SNR delta phi) was estimated in skeletal muscle and kidney cortex in 10 rabbits. Optimized parameters included the echo time equivalent to T2* of the tissue, the longest repetition time possible with a 20-s sonication, and the flip angle equivalent to the Ernst angle. Optimal SPGR phase imaging can detect a sonication beam with a peak phase difference of 0.55 radian, which corresponds to a temperature elevation of 7.3 degrees C. The sonication beam can be localized within one voxel (0.6 x 0.6 x 5 mm3) at power levels that are below the threshold for thermal damage of the tissue.

A clinical, noninvasive, MR imaging-monitored ultrasound surgery method.

A noninvasive method of tissue ablation that is guided and monitored with magnetic resonance (MR) imaging has been developed. The method uses sharply focused ultrasound transducers of different focal lengths to induce a localized temperature elevation during a short exposure (1-20 seconds). A hydraulic, computer-controlled positioning device moves the transducer in an MR imager. The positioner is built into a standard cradle in the imager. The system includes cavitation detection and power monitoring circuitry for patient safety. The target volume is outlined with cross-sectional MR images obtained immediately before sonication. By means of the software, the focus is moved to ablate the volume defined with the images. The temperature elevation during the exposure is monitored by means of the proton resonance frequency shift with fast gradient-echo sequences, and the necrosed volume is demonstrated with T2-weighted fast spin-echo images. This method has been extensively tested in in vivo animal experiments and is now undergoing clinical trial.

Potential adverse effects of high-intensity focused ultrasound exposure on blood vessels in vivo.

The aim of the study was to evaluate the potential adverse effects of high intensity ultrasound exposure on blood vessels during noninvasive focused ultrasound surgery. A hydraulic MR-compatible positioning device was used to manipulate a focused ultrasound transducer (frequency 1.49 MHz, f-number = 0.8) in an MRI scanner. The system was used to sonicate a branch of the femoral artery and vein of 19 rabbits (26 thighs) in vivo at intensity levels above the threshold for transient cavitation; i.e., between 4400 and 8800 W cm-2 with multiple 1 s pulses stepped across the vessels (step size = 0.7 mm). The vessels were located and followed by MR angiography. In 13 rabbits, x-ray angiograms were also performed after the animals were euthanized. The results demonstrated that the 1 s high-intensity exposures caused the arteries to constrict at all exposure levels tested. At the intensity of 5800 W cm-2 and above, the MRI angiogram immediately after the sonications showed no flow. The x-ray angiograms (1-2 h later) showed that the blood vessels were open, but constricted to about 50% or less of their diameter. Both the MR and x-ray angiograms showed that the vessel diameters relaxed toward their initial diameter during the first week after sonication. In five cases, hemorrhage or vessel rupture was caused by the sonication. This study demonstrates that short, high-intensity focused ultrasound exposure can cause vessel spasm and hemorrhage when transient cavitation is present. This condition should be avoided during noninvasive focused ultrasound surgery.