Magnetic resonance imaging enhanced by superparamagnetic iron oxide particles: Usefulness for distinguishing between focused ultrasound‐induced blood–brain barrier disruption and brain hemorrhage

Purpose

To investigate the usefulness of a fully flow‐compensated heavy T2*‐weighted imaging enhanced by superparamagnetic iron oxide (SPIO) particles for distinguishing between focused ultrasound‐induced disruption of blood–brain barrier (BBB) and brain hemorrhage.

Materials and Methods

Focused ultrasound (frequency: 1.5 MHz) was used to induce disruption of the BBB in 39 rats. Two T2*‐weighted images were obtained before and after SPIO administration. Preenhanced T2*‐weighted images were used to detect hemorrhage. Detection of BBB disruption was performed on SPIO‐enhanced images. Thirty‐four rats were sacrificed after magnetic resonance (MR) scanning for histological confirmation of brain lesions. Theremaining five animals were followed up for 35 days. Prussian blue staining was performed on histological sections to detect SPIO particles in the brain.

Results

After SPIO injection the areas of BBB disruption in rat brain were significantly enlarged. The area of mismatch between the T2*‐weighted images indicated a safe region where BBB opening occurred without hemorrhagic complications. In the longitudinal study, removal of SPIO occurred at a faster rate in hemorrhagic areas, albeit being closer to that occurring in the liver. The presence of SPIO was confirmed by Prussian blue staining in brain parenchyma and capillary endothelial cells in areas of BBB disruption.

Conclusion

T2*‐weighted images—either with and without SPIO enhancement—may differentiate focused ultrasound‐induced BBB disruption from brain hemorrhage. J. Magn. Reson. Imaging 2009;29:31–38. © 2008 Wiley‐Liss, Inc.     

Association between contrast‐enhanced MR images and blood–brain barrier disruption following transcranial focused ultrasound

Purpose:

To investigate the correlation between the contrast‐enhanced magnetic resonance imaging (MRI) signal and the duration of blood–brain barrier (BBB) disruption induced by focused ultrasound (FUS).

Materials and Methods:

FUS was applied to 45 rat brains in the presence of microbubbles, and these rats were scanned on a 3T MRI system at several timepoints. The rat brains were then studied using contrast‐enhanced spin echo T1‐weighted images. At the same time, BBB disruption was evaluated based on Evans blue (EB) extravasation. The relationship between the normalized signal intensity change of the MRI and EB extravasation was analyzed by least‐squares linear regression and the calculation of correlation coefficients.

Results:

When MRI enhancement was quantitatively evaluated by EB extravasation, a strong correlation between the normalized signal intensity change of the MRI and EB extravasation was identified during BBB disruption after sonication. However, the correlation coefficient decreased as BBB closure occurred after sonication ended.

Conclusion:

The contrast‐enhanced MRI signal can potentially be used to evaluate the amount of chemotherapeutic agents entering the targeted tissue, but the accuracy of the assessment will be affected by the time interval since sonication. J. Magn. Reson. Imaging 2010;32:593–599. © 2010 Wiley‐Liss, Inc.     

Low‐intensity pulsed ultrasound increases cellular uptake of superparamagnetic iron oxide nanomaterial: Results from human osteosarcoma cell line U2OS

Purpose:

To determine whether low‐intensity pulsed ultrasound (LIPUS) is able to facilitate the uptake of a superparamagnetic iron oxide (SPIO) nanomaterial by cells that do not express high endocytosis capacity.

Materials and Methods:

The human osteosarcoma cell line U2OS and a silica‐coated SPIO functionalized peripherally with amines groups (overall diameter 8 nm) were used in this study. Adherent U2OS cells were labeled with SPIO by incubating with culture media containing the SPIO at 4.5 μg[Fe]/mL. LIPUS with the same parameters as those used in clinical application to accelerate bone fracture healing (1.5 MHz, duty cycle 1:4, spatial‐average temporal‐average intensity 30 mW/cm²) was applied to the cells at the beginning of the labeling process for 0, 0.5, 1, or 3 hours. The total incubation time with SPIO was 12 hours. SPIO labeling efficiency was evaluated with Prussian blue staining and a blueness measurement method, and magnetic resonance imaging (MRI) of cell pellets via measuring areas of SPIO‐induced signal void.

Results:

Both Prussian blue staining and in vitro MRI demonstrated that LIPUS application increased the SPIO nanomaterial labeling efficiency for U2OS cells in an exposure‐duration‐dependent manner.

Conclusion:

This study is a “proof of concept” that LIPUS can facilitate the cellular take‐up of SPIO nanomaterial. J. Magn. Reson. Imaging 2010;31:1508–1513. © 2010 Wiley‐Liss, Inc.     

Pulse sequence and timing of contrast‐enhanced MRI for assessing blood–brain barrier disruption after transcranial focused ultrasound in the presence of hemorrhage

Purpose:

To optimize the timing of contrast‐enhanced magnetic resonance imaging (MRI) that best indicates blood–brain barrier (BBB) disruption induced by focused ultrasound (FUS) along with an ultrasound contrast agent (UCA) and to verify that the contrast‐enhanced spin‐echo MRI sequence can indicate the degree and location of BBB disruption in the presence of hemorrhage better than a gradient‐echo sequence.

Materials and Methods:

Sonication was applied to 12 rat brains with four different doses of UCA to cause variable degrees of hemorrhage. Two imaging sequences were performed to acquire T1‐weighted (T1W) images at two time‐points after the administration of a T1‐shortening contrast agent. The contrast enhancement at the sonicated regions was quantified and correlated against Evans blue (EB) staining.

Results:

The spin‐echo T1W images at 10 minutes post–contrast enhancement showed the best correlation with EB staining in both quantity of EB extravasation (r = 0.812; P < 0.01) and spatial distribution (r = 0.528, P < 0.01). This capability was more robust than the gradient‐echo sequence.

Conclusion:

Our results suggest that contrast‐enhanced T1W spin‐echo sequence acquired in the early phase post–contrast enhancement should be considered to monitor the degree and location of BBB disruption under the possibility of hemorrhage induced by FUS. J. Magn. Reson. Imaging 2010;31:1323–1330. © 2010 Wiley‐Liss, Inc.     

An experimental study on MR imaging of atherosclerotic plaque with SPIO marked endothelial cells in a rabbit model

Purpose:

To investigate how to label macrophages in atherosclerotic plaques with superparamagnetic iron oxide (SPIO) nanoparticles and trace SPIO with MR imaging.

Materials and Methods:

Atherosclerotic lesions of a rabbit model were induced by a combination of high‐fat and high‐cholesterol diet and subsequent endothelial abrasion of the abdominal aorta. SPIO particles were pretreated with poly‐L‐lysine. SPIO nanoparticles and SPIO‐labeled human endothelial cells (ECV‐304) were IV injected into model animals, respectively. The MRI scans and histopathological examination were performed 12 h and 24 h after the injection. The imaging and histopathological data were analyzed.

Results:

Prussian blue staining of the vessel specimens indicated that SPIO particles were not found in the atheroma but in the Kupffer's cells of the liver after SPIO injection. However, the accumulation of SPIO particles in the atheroma was confirmed in animals received SPIO‐labeled endothelial cell transplantation. The best quality MR scan sequences of rabbit abdominal aorta were T₂WI fat suppression, T₁WI, and DIR series, on which of MR image had a higher quality. Signal loss of the original incrassate plaque in the vessel wall on T₂WI was found in 6 of 10 animals received SPIO‐labeled endothelial cell transplantation.

Conclusion:

SPIO‐labeled endothelial cells were superior to SPIO for MR imaging of atherosclerotic plaques. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.     

Detection of hepatocellular carcinoma (HCC) using super paramagnetic iron oxide (SPIO)‐enhanced MRI: Added value of diffusion‐weighted imaging (DWI)

Purpose:

To evaluate whether diffusion‐weighted imaging (DWI) improves the detection of hepatocellular carcinoma (HCC) on super paramagnetic iron oxide (SPIO)‐enhanced MRI.

Materials and Methods:

This retrospective study group consisted of 30 patients with 50 HCC nodules who underwent MRI at 1.5 Tesla. Two combined MR sequence sets were compared for detecting HCC: SPIO‐enhanced MRI (axial T2‐weighted fast spin‐echo (FSE) and T1‐/T2*‐weighted fast field echo (FFE) scanned before and after administration of ferucarbotran) and SPIO‐enhanced MRI + DWI (SPIO‐enhanced MRI with axial DWI scanned before and after administration of ferucarbotran). Three blinded readers independently reviewed for the presence of HCC on a segment‐by‐segment basis using a four‐point confidence scale. The performance of the two combined MR sequence sets was evaluated using receiver operating characteristic (ROC) analysis.

Results:

The average area under the ROC curve (Az) of the three readers for the SPIO‐enhanced MRI + DWI set (0.870 ± 0.046) was significantly higher that that for the SPIO‐enhanced MRI set (0.820 ± 0.055) (P = .025). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for detection of HCC were 66.0%, 98.0%, 90.0%, and 91.4%, respectively, for the SPIO‐enhanced MRI set, and 70.0%, 98.6%, 92.9%, and 92.4%, respectively, for the SPIO‐enhanced MRI + DWI set.

Conclusion:

The SPIO‐enhanced MRI + DWI set outperformed the SPIO‐enhanced MRI set for depicting HCC. J. Magn. Reson. Imaging 2010; 31: 373–382. © 2010 Wiley‐Liss, Inc.     

Negatively charged superparamagnetic iron oxide nanoparticles: a new blood-pooling magnetic resonance contrast agent

Purpose

Our purpose was to investigate the utility of superparamagnetic iron-oxide nanoparticles (SPIO) as a blood-pooling contrast agent at magnetic resonance imaging (MRI).

Materials and methods

We studied four contrast agents: carboxymethyl-diethylaminoethyl dextran magnetite SPIO (CMEADM-S, diameter 54 nm), negatively charged CMEADM ultrasmall SPIO (CMEADM-U, 32 nm), alkali-treated dextran magnetite SPIO (ATDM-S, 55 nm), and ATDM ultrasmall SPIO (ATDM-U, 28 nm) carrying a neutral charge. Each contrast agent (80 μmol/kg) was injected intraperitoneally into apolipoprotein E (apoE) mice and the tissue iron concentration was measured 30-, 60-, 180-, and 300-min later by nuclear MR. For MR angiographic (MRA) evaluation, we injected the agents into the auricular vein of four groups of 15 rabbits. Immediately and 30-, 60-, 180-, and 300-min later, three rabbits from each group were subjected to MRI. The organ/background signal ratio (SR) was calculated. Statistical analyses were performed with Tukey’s honestly significant difference (HSD) test.

Results

At 60 and 180 min, blood-iron concentration of CMEADM-U was significantly different from other contrast agents. In the abdominal aorta and inferior vena cava, SR of CMEADM-U was higher at 180 and 300 min than of the other contrast agents. In the thoracic aorta, there was no difference in SR at 300 min between CMEADM-U and CMEADM-S.

Conclusion

Negatively charged SPIO nanoparticles may be useful as a blood-pooling contrast agent.     

Dual-temporal resolution dynamic contrast-enhanced MRI protocol for blood-brain barrier permeability measurement in enhancing multiple sclerosis lesions

Purpose:

To design a more accurate and reproducible technique for the measurement of blood–brain barrier (BBB) permeability in gadolinium‐enhancing multiple sclerosis (MS) lesions.

Materials and Methods:

Four MS patients were scanned using a new dynamic contrast‐enhanced (DCE)‐magnetic resonance imaging (MRI) protocol based on an uninterrupted two‐part acquisition consisting of an initial part at high temporal and low spatial resolutions and a second part at low temporal and high spatial resolutions. The method preserves both the high spatial resolution needed for the often small size of lesions and the high temporal resolution required during the first minute after injection to sufficiently sample the first‐pass bolus. Simulations compared the performance of this new protocol with the conventional one at low temporal and high spatial resolutions throughout.

Results:

The BBB permeability estimates changed by up to 33% between the two protocols. The new protocol led to simulated error on K^trans of 7%–10%, versus 7%–30% with the conventional protocol, and was more robust with respect to offsets between acquisition and injection start times, differences in shape of the first‐pass peak, and permeability values.

Conclusion:

The dual‐temporal resolution protocol produces improved BBB permeability estimates and provides a more complete view of active inflammatory MS lesion pathology. J. Magn. Reson. Imaging 2011;33:1291–1300. © 2011 Wiley‐Liss, Inc.     

Diagnosis of colorectal hepatic metastases: comparison of contrast-enhanced CT, contrast-enhanced US, superparamagnetic iron oxide-enhanced MRI, and gadoxetic acid-enhanced MRI

Purpose:

To compare the diagnostic accuracy of contrast‐enhanced computed tomography (CE‐CT), contrast‐enhanced ultrasonography (CE‐US), superparamagnetic iron oxide‐enhanced magnetic resonance imaging (SPIO‐MRI), and gadoxetic acid‐enhanced MRI (Gd‐EOB‐MRI) in the evaluation of colorectal hepatic metastases.

Materials and Methods:

In all, 111 patients with colorectal cancers were enrolled in this study. Of the 112 metastases identified in 46 patients, 31 in 18 patients were confirmed histologically and the remaining 81 in 28 patients were confirmed by follow‐up imaging. CE‐CT, CE‐US, SPIO‐MRI, and Gd‐EOB‐MRI were evaluated. Mean (of three readers, except for CE‐US) area under the receiver operating characteristic curve (A_z), sensitivities, and positive predictive values (PPV) were calculated. Each value was compared to the others by variance z‐test or chi‐square test with Bonferroni correction.

Results:

For all lesions, mean A_z and sensitivity of Gd‐EOB‐MRI (0.992, 95% [56/59]) were significantly greater than those of CE‐CT (0.847, 63% [71/112]) and CE‐US (0.844, 73% [77/106]). For lesions ≤1 cm, mean A_z and sensitivity of Gd‐EOB‐MRI (0.999, 92% [22/24]) were significantly greater than those of CE‐CT (0.685, 26% [13/50]) and CE‐US (0.7, 41% [18/44]). Mean A_z (95% CI) of SPIO‐MRI for all lesions (0.966 [0.929–0.987]) and lesions ≤ 1 cm (0.961 [0.911–0.988]) were significantly greater than those of CE‐CT and CE‐US. Mean sensitivity of SPIO‐MRI for lesions ≤1 cm (63%, 26/41) was significantly greater than that of CE‐CT.

Conclusion:

Gd‐EOB‐MRI and SPIO‐MRI were more accurate than CE‐CT and CE‐US for evaluation of liver metastasis in patients with colorectal carcinoma. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.     

Comparison of ferucarbotran‐enhanced fluid‐attenuated inversion‐recovery echo‐planar,T2‐weighted turbo spin‐echo,T2*‐weighted gradient‐echo,and diffusion‐weighted echo‐planar imaging for detection of malignant liver lesions

Purpose:

To compare the diagnostic accuracy of superparamagnetic iron oxide (SPIO)‐enhanced fluid‐attenuated inversion‐recovery echo‐planar imaging (FLAIR EPI) for malignant liver tumors with that of T2‐weighted turbo spin‐echo (TSE), T2*‐weighted gradient‐echo (GRE), and diffusion‐weighted echo‐planar imaging (DW EPI).

Materials and Methods:

SPIO‐enhanced magnetic resonance imaging (MRI) that included FLAIR EPI, T2‐weighted TSE, T2*‐weighted GRE, and DW EPI sequences was performed using a 3 T system in 54 consecutive patients who underwent surgical exploration with intraoperative ultrasonography. A total of 88 malignant liver tumors were evaluated. Images were reviewed independently by two blinded observers who used a 5‐point confidence scale to identify lesions. Results were correlated with results of histopathologic findings and surgical exploration with intraoperative ultrasonography. The accuracy of each MRI sequence was measured with jackknife alternative free‐response receiver operating characteristic analysis. The sensitivity of each observer with each MRI sequence was compared with McNemar's test.

Results:

Accuracy values were significantly higher with FLAIR EPI sequence (0.93) than with T2*‐weighted GRE (0.80) or DW EPI sequences (0.80) (P < 0.05). Sensitivity was significantly higher with the FLAIR EPI sequence than with any of the other sequences.

Conclusion:

SPIO‐enhanced FLAIR EPI sequence was more accurate in the diagnosis of malignant liver tumors than T2*‐weighted GRE and DW EPI sequences. SPIO‐enhanced FLAIR EPI sequence is helpful for the detection of malignant liver tumors. J. Magn. Reson. Imaging 2010;31:607–616. ©2010 Wiley‐Liss, Inc.     

Evaluation of referenceless thermometry in MRI-guided focused ultrasound surgery of uterine fibroids

Purpose

To clinically assess a previously described method (Rieke et.al., Magn Reson Med 2004) to produce more motion‐robust MRI‐based temperature images using data acquired during MRI‐guided focused ultrasound surgery (MRgFUS) of uterine fibroids.

Materials and Methods

The method (“referenceless thermometry”) uses surface fitting in nonheated regions of individual phase images to extrapolate and then remove background phase variations that are unrelated to temperature changes. We tested this method using images from 100 sonications selected from 33 patient MRgFUS treatments. Temperature measurements and thermal dose contours estimated with the referenceless method were compared with those produced with the standard phase‐difference technique. Fitting accuracy and noise level were also measured.

Results

In 92/100 sonications, the difference between the two measurements was less than 3°C. The average difference in the measurements was 1.5 ± 1.4°C. Small motion artifacts were observed in the phase‐difference imaging when the difference was greater than 3°C. The method failed in two cases. The mean absolute error in the surface fit in baseline images corresponded to a temperature error of 0.8 ± 1.4°C. The noise level was approximately 40% lower than the phase‐difference method. Thermal dose contours calculated from the two methods agreed well on average.

Conclusion

Based on the small error when compared with the standard technique, this method appears to be adequate for temperature monitoring of MRgFUS in uterine fibroids and may prove useful for monitoring temperature changes in moving organs. J. Magn. Reson. Imaging 2008;28:1026–1032. © 2008 Wiley‐Liss, Inc.     

Differentiation of well‐differentiated hepatocellular carcinomas from other hepatocellular nodules in cirrhotic liver: Value of SPIO‐enhanced MR imaging at 3.0 Tesla

Purpose

To determine the diagnostic value of superparamagnetic iron oxide (SPIO)‐enhanced MRI for the differentiation of well‐differentiated hepatocellular carcinomas (WD‐HCCs) from other hepatocellular nodules in cirrhotic liver.

Materials and Methods

This study included 114 patients with 216 histologically confirmed hepatocellular nodules, i.e., 23 dysplastic nodules (DNs), 37 WD‐HCCs, and 156 moderately or poorly differentiated HCCs (MD‐/PD HCCs), who underwent SPIO‐enhanced MRI at 3.0T. MRI included T2‐weighted fast‐spin echo and T2*‐weighted gradient recalled echo (GRE) sequences before and after administration of ferucarbotran. The contrast‐to‐noise ratio (CNR) of the lesion was calculated. Reviewers analyzed signal intensity (SI) of the nodules and their enhancement features on SPIO‐enhanced images. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy in the diagnosis of WD‐HCC were also calculated.

Results

The mean CNR of WD‐HCC was significantly higher than that of DN on T2*‐weighted image. Incomplete high SI on SPIO‐enhanced T2*‐weighted images were seen in 56.8% of WD‐HCC. The most prevalent enhancement features of WD‐HCCs on SPIO‐enhanced T2*‐weighted images, were iso SI with high SI foci [32.5% (12/37)] and homogenous subtle high SI [24.3% (9/37)]. Alternatively, 22 of 23 DNs (95.7%) showed low‐ or iso SI, and 145 of 156 (94.9%) MD‐/PD HCCs showed strong high SI. When iso SI with high SI foci or subtle homogenous high SI nodule was considered as diagnostic criteria for WD‐HCC, we could identify 56.8% of the WD‐HCCs but only 4.4% of the DNs and 3.2% of the MD‐/PD HCCs.

Conclusion

WD‐HCCs have characteristic enhancement features that differentiate them from DNs and MD‐/PD HCCs on SPIO‐enhanced 3.0T MRI. The lesion conspicuity was better on T2*‐weighted images than that on T2‐weighted images. J. Magn. Reson. Imaging 2009;29:328–335. © 2009 Wiley‐Liss, Inc.     

Supine breast MRI

Purpose:

To achieve high‐quality unilateral supine breast magnetic resonance imaging (MRI) as a step to facilitate image aiding of clinical applications, which are often performed in the supine position. Contrast‐enhanced breast MRI is a powerful tool for the diagnosis of cancer. However, prone patient positioning typically used for breast MRI hinders its use for image aiding.

Materials and Methods:

A fixture and a flexible four‐element receive coil were designed for patient‐specific shaping and placement of the coil in close conformity to the supine breast. A 3D spoiled gradient sequence was modified to incorporate compensation of respiratory motion. The entire setup was tested in volunteer experiments and in a pilot patient study.

Results:

The flexible coil design and the motion compensation produced supine breast MR images of high diagnostic value. Variations in breast shape and in tissue morphology within the breast were observed between a supine and a diagnostic prone MRI of a patient.

Conclusion:

The presented supine breast MRI achieved an image quality comparable to diagnostic breast MRI. Since supine positioning is common in many clinical applications such as ultrasound‐guided breast biopsy or breast‐conserving surgery, the registration of the supine images will aid these applications. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.     

Cavernosal nerve functionality evaluation after magnetic resonance imaging-guided transurethral ultrasound treatment of the prostate

AIM: To evaluate the feasibility of using therapeutic ultrasound as an alternative treatment option for organ-confined prostate cancer.METHODS: In this study, a trans-urethral therapeutic ultrasound applicator in combination with 3T magnetic resonance imaging (MRI) guidance was used for real-time multi-planar MRI-based temperature monitoring and temperature feedback control of prostatic tissue thermal ablation in vivo. We evaluated the feasibility and safety of MRI-guided trans-urethral ultrasound to effectively and accurately ablate prostate tissue while minimizing the damage to surrounding tissues in eight canine prostates. MRI was used to plan sonications, monitor temperature changes during therapy, and to evaluate treatment outcome. Real-time temperature and thermal dose maps were calculated using the proton resonance frequency shift technique and were displayed as two-dimensional color-coded overlays on top of the anatomical images. After ultrasound treatment, an evaluation of the integrity of cavernosal nerves was performed during prostatectomy with a nerve stimulator that measured tumescence response quantitatively and indicated intact cavernous nerve functionality. Planned sonication volumes were visually correlated to MRI ablation volumes and corresponding histo-pathological sections after prostatectomy.RESULTS: A total of 16 sonications were performed in 8 canines. MR images acquired before ultrasound treatment were used to localize the prostate and to prescribe sonication targets in all canines. Temperature elevations corresponded within 1 degree of the targeted sonication angle, as well as with the width and length of the active transducer elements. The ultrasound treatment procedures were automatically interrupted when the temperature in the target zone reached 56 °C. In all canines erectile responses were evaluated with a cavernous nerve stimulator post-treatment and showed a tumescence response after stimulation with an electric current. These results indicated intact cavernous nerve functionality. In all specimens, regions of thermal ablation were limited to areas within the prostate capsule and no damage was observed in periprostatic tissues. Additionally, a visual analysis of the ablation zones on contrast-enhanced MR images acquired post ultrasound treatment correlated excellent with the ablation zones on thermal dose maps. All of the ablation zones received a consensus score of 3 (excellent) for the location and size of the correlation between the histologic ablation zone and MRI based ablation zone. During the prostatectomy and histologic examination, no damage was noted in the bladder or rectum.CONCLUSION: Trans-urethral ultrasound treatment of the prostate with MRI guidance has potential to safely, reliably, and accurately ablate prostatic regions, while minimizing the morbidities associated with conventional whole-gland resection or therapy.     

Volumetric MRI‐guided high‐intensity focused ultrasound for noninvasive,in vivo determination of tissue thermal conductivity: Initial experience in a pig model

Purpose:

To estimate the local thermal conductivity of porcine thigh muscle at temperatures required for magnetic resonance imaging (MRI)‐guided high‐intensity focused ultrasound (MRgHIFU) surgery (60–90°C).

Materials and Methods:

Using MRgHIFU, we performed 40 volumetric ablations in the thigh muscles of four pigs. Thirty‐five of the sonications were successful. We used MRI to monitor the resulting temperature increase. We then determined local thermal conductivity by analyzing the spatiotemporal spread of temperature during the cooling period.

Results:

The thermal conductivity of MRgHIFU‐treated porcine thigh muscle fell within a narrow range (0.52 ± 0.05 W/[m*K]), which is within the range reported for porcine thigh muscle at temperatures of <40°C (0.52 to 0.62 W/[m*K]). Thus, there was little change in the thermal conductivity of porcine thigh muscle at temperatures required for MRgHIFU surgery compared to lower temperatures.

Conclusion:

Our MRgHIFU‐based approach allowed us to estimate, with good reproducibility, the local thermal conductivity of in vivo deep tissue in real time at temperatures of 60°C to 90°C. Therefore, our method provides a valuable tool for quantifying the influence of thermal conductivity on temperature distribution in tissues and for optimizing thermal dose delivery during thermal ablation with clinical MRgHIFU. J. Magn. Reson. Imaging 2013;37:950–957. © 2012 Wiley Periodicals, Inc.     

Evaluating the severity of nonalcoholic steatohepatitis with superparamagnetic iron oxide‐enhanced magnetic resonance imaging

Purpose

To evaluate the utility of noninvasive assessment of human nonalcoholic fatty liver disease (NAFLD) patients using superparamagnetic iron oxide (SPIO)‐enhanced MRI.

Materials and Methods

Nineteen NAFLD patients underwent SPIO‐enhanced MRI. The values of τ, a time constant for an exponential approximation, were calculated using gradient‐echo echo‐planar imaging, and the values of %T2, a marker of the T2 relaxation effect of SPIO, were calculated using T2‐weighted fast spin‐echo images. Correlations between these values and the histological NAFLD activity scores were evaluated. The study protocol was approved by our Institutional Review Board and all patients gave informed consent.

Results

There was a statistically significant relationship between the NAFLD activity scores and the τ values (r = 0.66, P = 0.002). The %T2 values were also significantly correlated with the NAFLD activity score (r = ?0.58, P = 0.009). A cutoff τ value of 42.8 predicted “definitive NASH” (NAFLD activity score ≥5) with a specificity of 66.7% and a sensitivity of 99.9%, whereas a cutoff %T2 value of 32.5 predicted “definitive NASH” with a specificity of 72.7% and a sensitivity of 87.5%.

Conclusion

Noninvasive SPIO‐enhanced MRI may be helpful for identifying NASH patients among patients suspected of having NAFLD. J. Magn. Reson. Imaging 2008;28:1444–1450. © 2008 Wiley‐Liss, Inc.

     

Factors contributing to blood–brain barrier disruption following intracarotid injection of nonionic iodinated contrast medium for cerebral angiography: experimental study in rabbits

Purpose

This study was performed to investigate the role of injection methods and conditions under a fixed dose of radiographic contrast medium (CM) in respect to promoting blood–brain barrier (BBB) disruption.

Materials and methods

A total of 44 white rabbits (average body weight 2.7 ± 0.4?kg) were used, and their carotid injection was performed with nonionic CM. The variables assessed for the carotid injections included the following: iodine content (300 or 150?mg?I/ml), liquid temperature (37° or 24°C), and the injection time duration (1 or 30?s). The rabbits were divided into five groups. To evaluate BBB disruption, pre- and post-contrast-enhanced magnetic resonance (MR) studies were performed.

Results

Abnormal enhancement of the brain parenchyma in MRI was noted in only one group, which consisted of high-iodine concentration CM injected at a low temperature over a short injection interval. Statistically significant increased values for the percentage of relative enhancement (RE%) were demonstrated (P < 0.05) in comparison with the saline-injected control group.

Conclusion

This result suggests variables that may need to be carefully considered to prevent BBB injury induced by nonionic CM for cerebral angiography, especially in the setting of a neurointerventional procedure.     

Adaptive noise cancellation to suppress electrocardiography artifacts during real-time interventional MRI

Purpose:

To develop a system for artifact suppression in electrocardiogram (ECG) recordings obtained during interventional real‐time magnetic resonance imaging (MRI).

Materials and Methods:

We characterized ECG artifacts due to radiofrequency pulses and gradient switching during MRI in terms of frequency content. A combination of analog filters and digital least mean squares adaptive filters were used to filter the ECG during in vivo experiments and the results were compared with those obtained with simple low‐pass filtering. The system performance was evaluated in terms of artifact suppression and ability to identify arrhythmias during real‐time MRI.

Results:

Analog filters were able to suppress artifacts from high‐frequency radiofrequency pulses and gradient switching. The remaining pulse artifacts caused by intermittent preparation sequences or spoiler gradients required adaptive filtering because their bandwidth overlapped with that of the ECG. Using analog and adaptive filtering, a mean improvement of 38 dB (n = 11, peak QRS signal to pulse artifact noise) was achieved. This filtering system was successful in removing pulse artifacts that obscured arrhythmias such as premature ventricular complexes and complete atrioventricular block.

Conclusion:

We have developed an online ECG monitoring system employing digital adaptive filters that enables the identification of cardiac arrhythmias during real‐time MRI‐guided interventions. J. Magn. Reson. Imaging 2011;33:1184–1193. © 2011 Wiley‐Liss, Inc.     

Pre-operative sentinel lymph node localization in breast cancer with superparamagnetic iron oxide MRI: the SentiMAG Multicentre Trial imaging subprotocol

Objective:

Sentinel lymph node biopsy (SLNB) with a superparamagnetic iron oxide (SPIO) tracer was shown to be non-inferior to the standard combined technique in the SentiMAG Multicentre Trial. The MRI subprotocol of this trial aimed to develop a magnetic alternative for pre-operative lymphoscintigraphy (LS). We evaluated the feasibility of using MRI following the administration of magnetic tracer for pre-operative localization of sentinel lymph nodes (SLNs) and its potential for non-invasive identification of lymph node (LN) metastases.

Methods:

Patients with breast cancer scheduled to undergo SLNB were recruited for pre-operative LS, single photon emission CT (SPECT)-CT and SPIO MRI. T₁ weighted turbo spin echo and T₂ weighted gradient echo sequences were used before and after interstitial injection of magnetic tracer into the breast. SLNs on MRI were defined as LNs with signal drop and direct lymphatic drainage from the injection site. LNs showing inhomogeneous SPIO uptake were classified as metastatic. During surgery, a handheld magnetometer was used for SLNB. Blue or radioactive nodes were also excised. The number of SLNs and MR assessment of metastatic involvement were compared with surgical and histological outcomes.

Results:

11 patients were recruited. SPIO MRI successfully identified SLNs in 10 of 11 patients vs 11 of 11 patients with LS/SPECT-CT. One patient had metastatic involvement of four LNs, and this was identified in one node on pre-operative MRI.

Conclusion:

SPIO MRI is a feasible technique for pre-operative localization of SLNs and, in combination with intraoperative use of a handheld magnetometer, provides an entirely radioisotope-free technique for SLNB. Further research is needed for the evaluation of MRI characterization of LN involvement using subcutaneous injection of magnetic tracer.

Advances in knowledge:

This study is the first to demonstrate that an interstitially administered magnetic tracer can be used both for pre-operative imaging and intraoperative SLNB, with equal performance to imaging and localization with radioisotopes.     

In vivo vascular hallmarks of diffuse leukoaraiosis

Purpose:

To characterize multiple patterns of vascular changes in leukoaraiosis using in vivo magnetic resonance imaging (MRI) techniques.

Materials and Methods:

We measured cerebral blood flow (CBF), cerebrovascular reactivity (CVR), and blood–brain‐barrier (BBB) leakage in a group of 33 elderly subjects (age: 72.3 ± 6.8 years, 17 males, 16 females). Leukoaraiosis brain regions were identified in each subject using fluid‐attenuated inversion‐recovery (FLAIR) MRI. Vascular parameters in the leukoaraiosis regions were compared to those in the normal‐appearing white matter (NAWM) regions. Vascular changes in leukoaraiosis were also compared to structural damage as assessed by diffusion tensor imaging.

Results:

CBF and CVR in leukoaraiosis regions were found to be 39.7 ± 5.2% (P < 0.001) and 52.5 ± 11.6% (P = 0.005), respectively, of those in NAWM. In subjects who did not have significant leukoaraiosis, CBF and CVR in regions with high risk for leukoaraiosis showed a slight reduction compared to the other white matter regions. Significant BBB leakage was also detected (P = 0.003) in leukoaraiosis and the extent of BBB leakage was positively correlated with mean diffusivity. In addition, CVR in NAWM was lower than that in white matter of subjects without significant leukoaraiosis.

Conclusion:

Leukoaraiosis was characterized by reduced CBF, CVR, and a leakage in the BBB. J. Magn. Reson. Imaging 2010;32:184–190. © 2010 Wiley‐Liss, Inc.