A quantitative pressure and microbubble‐size dependence study of focused ultrasound‐induced blood‐brain barrier opening reversibility in vivo using MRI

Focused ultrasound in conjunction with the systemic administration of microbubbles has been shown to open the blood‐brain barrier (BBB) selectively, noninvasively and reversibly. In this study, we investigate the dependence of the BBB opening's reversibility on the peak‐rarefactional pressure (0.30–0.60 MPa) as well as the microbubble size (diameters of 1–2, 4–5, or 6–8 μm) in mice using contrast‐enhanced T₁‐weighted (CE‐T₁) MR images (9.4 T). Volumetric measurements of the diffusion of Gd‐DTPA‐BMA into the brain parenchyma were used for the quantification of the BBB‐opened region on the day of sonication and up to 5 days thereafter. The volume of opening was found to increase with both pressure and microbubble diameter. The duration required for closing was found to be proportional to the volume of opening on the day of opening, and ranged from 24 h, for the smaller microbubbles, to 5 days at high peak‐rarefactional pressures. Overall, larger bubbles did not show significant differences. Also, the extent of BBB opening decreased radially towards the focal region until the BBB's integrity was restored. In the cases where histological damage was detected, it was found to be highly correlated with hyperintensity on the precontrast T₁ images. Magn Reson Med, 2012. © 2011 Wiley Periodicals, Inc.     

Quantitative measurement of N‐acetyl‐aspartyl‐glutamate at 3 T using TE‐averaged PRESS spectroscopy and regularized lineshape deconvolution

This article introduces regularized lineshape deconvolution in conjunction with TE‐averaged PRESS spectroscopy to measure N‐acetyl‐aspartyl‐glutamate (NAAG). Averaging different echo times suppressed the signals of multiplets from strongly coupled spin systems near 2 ppm; thus, minimizing the interfering signals to detect the acetyl proton signal of NAAG. Signal distortion was corrected by lineshape deconvolution, and Tikhonov regularization was introduced to reduce noise amplification arising from deconvolution; as a result, spectral resolution was enhanced without significantly sacrificing signal‐to‐noise ratio (SNR). This new approach was used to measure NAAG in the two regions of interest of healthy volunteers, dominated by gray matter and white matter, respectively. The acetyl proton signal of NAAG was directly quantified by fitting the deconvoluted spectra to a Voigt‐lineshape spectral model function, yielding the NAAG–N‐acetyl‐aspartate (NAA) ratios of 0.11 ± 0.02 for the gray matter voxels (n = 8) and 0.18 ± 0.02 for the white matter voxels (n = 12). Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

Chemical-shift-selective filter for the in vivo detection of J-coupled metabolites at 3T.

A chemical-shift-selective filter (CSSF) was applied to the detection of J-coupled metabolites in the human brain. This filter is an acquisition-based technique that requires the chemical shifts (CS's) of different metabolites, but not their whole multiplet structures, to be resolved. The sequence is based on the 2D constant-time spin-echo experiment, which yields pure CS spectra in the indirect dimension. Localization is achieved through point-resolved spectroscopy (PRESS). The method enables unequivocal detection of glutamate and myo-inositol, both in vitro and in vivo in the human brain, at 3T.     

Eddy‐current compensated diffusion weighting with a single refocusing RF pulse

A modification of the Stejskal‐Tanner diffusion‐weighting preparation with a single refocusing RF pulse is presented which involves three gradient lobes that can be adjusted to null eddy currents with any given decay rate to reduce geometric distortions in diffusion‐weighted echo‐planar imaging (EPI). It has a very similar compensation performance as the commonly used double‐spin‐echo preparation but (i) is less sensitive to flip angle imperfections, e.g. along the slice profile, and B₁ inhomogeneities and (ii) can yield shorter echo times for moderate b values, notably for longer echo trains as required for higher spatial resolution. It therefore can provide an increased signal‐to‐noise ratio as is simulated numerically and demonstrated experimentally in water phantoms and the human brain for standard EPI (2.0 × 2.0 mm²) and high‐resolution EPI of inner field‐of‐views using 2D‐selective RF excitations (0.5 × 1.0 mm²). Thus, the presented preparation may help to overcome current limitations of diffusion‐weighted EPI, in particular at high static magnetic fields. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Comparison of Gd-DTPA and Gd-BOPTA for studying renal perfusion and filtration

Purpose:

To measure the systematic error in perfusion and filtration parameters derived from magnetic resonance (MR) renography caused by protein binding of MR contrast agents.

Materials and Methods:

Eight healthy Danish Landrace pigs were examined with dynamic contrast‐enhanced magnetic resonance imaging (DCE‐MRI). In four pigs a bolus of gadopentetate‐dimeglumine (Gd‐DTPA; no protein binding) was injected, followed by gadobenate‐dimeglumine (Gd‐BOPTA; 10% protein binding). The order was reversed in the other four pigs. A two‐compartment filtration model was generalized to allow for protein binding and fitted to whole‐cortex region of interest (ROI) curves. Single‐kidney plasma flow and volume, tubular flow (or GFR), and tubular transit time of both agents were compared.

Results:

The data show a strong systematic underestimation (P < 0.001) in GFR by Gd‐BOPTA (33 ± 7.2%), and no significant differences (P > 0.05) in plasma flow (2.2 ± 18%), plasma volume (?1.7 ± 7.8%) and tubular transit time (3.1 ± 7.2%). The order of injection had no significant effect.

Conclusion:

Theory and experiments agree that perfusion parameters of both agents are comparable, whereas GFR is underestimated with Gd‐BOPTA due to the dependence of relaxivity on protein content. Hence, GFR cannot be measured with protein‐bound contrast agents, but the proposed dual‐agent protocol may produce new functional indices measuring protein filtration. J. Magn. Reson. Imaging 2011;. © 2011 Wiley‐Liss, Inc.

     

Non‐contrast‐enhanced MR portography with time‐spatial labeling inversion pulses: Comparison of imaging with three‐dimensional half‐fourier fast spin‐echo and true steady‐state free‐precession sequences

Purpose

To compare and evaluate images acquired with two different MR angiography (MRA) sequences, three‐dimensional (3D) half‐Fourier fast spin‐echo (FSE) and 3D true steady‐state free‐precession (SSFP) combined with two time‐spatial labeling inversion pulses (T‐SLIPs), for selective and non‐contrast‐enhanced (non‐CE) visualization of the portal vein.

Materials and Methods

Twenty healthy volunteers were examined using half‐Fourier FSE and true SSFP sequences on a 1.5T MRI system with two T‐SLIPs, one placed on the liver and thorax, and the other on the lower abdomen. For quantitative analysis, vessel‐to‐liver contrast (Cv‐l) ratios of the main portal vein (MPV), right portal vein (RPV), and left portal vein (LPV) were measured. The quality of visualization was also evaluated.

Results

In both pulse sequences, selective visualization of the portal vein was successfully conducted in all 20 volunteers. Quantitative evaluation showed significantly better Cv‐l at the RPVs and LPVs in half‐Fourier FSE (P < 0.0001). At the MPV, Cv‐l was better in true SSFP, but was not statistically different. Visualization scores were significantly better only at branches of segments four and eight for half‐Fourier FSE (P = 0.001 and 0.03, respectively).

Conclusion

Both 3D half‐Fourier FSE and true SSFP scans with T‐SLIPs enabled selective non‐CE visualization of the portal vein. Half‐Fourier FSE was considered appropriate for intrahepatic portal vein visualization, and true SSFP may be preferable when visualization of the MPV is required. J. Magn. Reson. Imaging 2009;29:1140–1146. © 2009 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.     

In vivo MRI and histopathological assessment of tumor microenvironment in luminal-like and basal-like breast cancer xenografts

Purpose:

To explore tumor pathophysiology with special attention to the microenvironment in two molecular subtypes of human breast cancer using in vivo magnetic resonance imaging (MRI) and histopathology. The impact of tumor growth, size, and the influence of estradiol were also investigated.

Materials and Methods:

Two orthotopic and directly transplanted human breast cancer models representing luminal‐like and basal‐like molecular subtypes were characterized by dynamic contrast‐enhanced MRI and diffusion‐weighted MRI. Ex vivo measurements of vascularization, hypoxia, mitoses, and the level of VEGF activations were associated with the calculated in vivo MRI parameters of the tumors.

Results:

The vascular permeability and perfusion (K^trans) was significantly higher in basal‐like compared to luminal‐like tumors. These findings were confirmed by a 4‐fold higher proliferating microvessel density (pMVD) in basal‐like tumors, reflecting the difference in aggressiveness between the subtypes. No effect of tumor growth was observed during 6 days of growth in any of the models; however, large tumors had lower K^trans, higher extracellular extravascular volume fraction (v_e), and more hypoxia than medium‐sized tumors. Estradiol withdrawal induced increased K^trans, v_e, and tumor water diffusion (ADC) in luminal‐like tumors, corresponding to increased VEGFR2 activation, which is likely to cause increased tumor vessel permeability.

Conclusion:

These novel data confirm the potential of functional MRI methods to map histopathologically proven changes in breast tumor vasculature and microenvironment in vivo. J. Magn. Reson. Imaging 2012;35:1098‐1107. © 2011 Wiley Periodicals, Inc.