Continuous arterial spin labeling perfusion measurements using single shot 3D GRASE at 3 T.

Single shot 3D GRASE is less sensitive to field inhomogeneity and susceptibility effects than gradient echo based fast imaging sequences while preserving the acquisition speed. In this study, a continuous arterial spin labeling (CASL) pulse was added prior to the single shot 3D GRASE readout and quantitative perfusion measurements were carried out at 3 T, at rest and during functional activation. The sequence performance was evaluated by comparison with a CASL sequence with EPI readout. It is shown that perfusion measurements using CASL GRASE can be performed safely on humans at 3 T without exceeding the current RF power deposition limits. The maps of resting cerebral blood flow generated from the GRASE images are comparable to those obtained with the 2D EPI readout, albeit with better coverage in the orbitofrontal cortex. The sequence proved effective for functional imaging, yielding time series of images with improved temporal SNR with respect to EPI and group activation maps with increased significance levels. The method was further improved using parallel imaging techniques to provide increased spatial resolution and better separation of the gray-white matter cerebral blood flow maps.     

Permeability dependence study of the focused ultrasound‐induced blood–brain barrier opening at distinct pressures and microbubble diameters using DCE‐MRI

Blood–brain barrier opening using focused ultrasound and microbubbles has been experimentally established as a noninvasive and localized brain drug delivery technique. In this study, the permeability of the opening is assessed in the murine hippocampus after the application of focused ultrasound at three different acoustic pressures and microbubble sizes. Using dynamic contrast‐enhanced MRI, the transfer rates were estimated, yielding permeability maps and quantitative K_trans values for a predefined region of interest. The volume of blood–brain barrier opening according to the K_trans maps was proportional to both the pressure and the microbubble diameter. A K_trans plateau of ～0.05 min^?1 was reached at higher pressures (0.45 and 0.60 MPa) for the larger sized bubbles (4–5 and 6–8 μm), which was on the same order as the K_trans of the epicranial muscle (no barrier). Smaller bubbles (1–2 μm) yielded significantly lower permeability values. A small percentage (7.5%) of mice showed signs of damage under histological examination, but no correlation with permeability was established. The assessment of the blood–brain barrier permeability properties and their dependence on both the pressure and the microbubble diameter suggests that K_trans maps may constitute an in vivo tool for the quantification of the efficacy of the focused ultrasound‐induced blood–brain barrier opening. Magn Reson Med, 2011. © 2011 Wiley‐Liss, Inc.     

T2‐based arterial spin labeling measurements of blood to tissue water transfer in human brain

Purpose:

To investigate blood to tissue water transfer in human brain, in vivo and spatially resolved using a T2‐based arterial spin labeling (ASL) method with 3D readout.

Materials and Methods:

A T2‐ASL method is introduced to measure the water transfer processes between arterial blood and brain tissue based on a 3D‐GRASE (gradient and spin echo) pulsed ASL sequence with multiecho readout. An analytical mathematical model is derived based on the General Kinetic Model, including blood and tissue compartment, T1 and T2 relaxation, and a blood‐to‐tissue transfer term. Data were collected from healthy volunteers on a 3 T system. The mean transfer time parameter T_bl→ex (blood to extravascular compartment transfer time) was derived voxelwise by nonlinear least‐squares fitting.

Results:

Whole‐brain maps of T_bl→ex show stable results in cortical regions, yielding different values depending on the brain region. The mean value across subjects and regions of interest (ROIs) in gray matter was 440 ± 30 msec.

Conclusion:

A novel method to derive whole‐brain maps of blood to tissue water transfer dynamics is demonstrated. It is promising for the investigation of underlying physiological mechanisms and development of diagnostic applications in cerebrovascular diseases. J. Magn. Reson. Imaging 2013;37:332–342. © 2012 Wiley Periodicals, Inc.     

Detecting blood–brain barrier disruption within minimal hemorrhage following transcranial focused ultrasound: A correlation study with contrast‐enhanced MRI

Focused ultrasound combined with an intravascular ultrasound contrast agent can induce transient disruption of the blood–brain barrier, and the blood–brain barrier disruption can be detected by contrast‐enhanced MRI. There is, however, no study investigating the ability of various MR methods to detect focused ultrasound–induced blood–brain barrier disruption within minimal hemorrhage. Sonication was applied to 15 rat brains with four different doses of ultrasound contrast agent (0, 10, 30, or 50 μL/kg), and contrast‐enhanced T1‐weighted spin echo, gradient echo images, and longitudinal relaxation rate mapping along with effective transverse relaxation time–weighted and susceptibility‐weighted images were acquired. Volume‐of‐interest–based and threshold‐based analyses were performed to quantify the contrast enhancement, which was then correlated with the ultrasound contrast agent dose and with the amount of Evans blue extravasation. Both effective transverse relaxation time–weighted and susceptibility‐weighted images did not detect histology‐proved intracranial hemorrhage at 10 μL/kg, but MRI failed to detect mild intracranial hemorrhage at 30 μL/kg. All tested sequences showed detectable contrast enhancement increasing with ultrasound contrast agent dose. In correlating with Evans blue extravasation, the gradient echo sequence was slightly better than the spin echo sequence and was comparable to longitudinal relaxation rate mapping. In conclusion, both gradient echo and spin echo sequences were all reliable in indicating the degree of focused ultrasound–induced blood–brain barrier disruption within minimal hemorrhage. Magn Reson Med, 2011. © 2010 Wiley‐Liss, Inc.     

Measurement of brain perfusion,blood volume,and blood‐brain barrier permeability,using dynamic contrast‐enhanced T1‐weighted MRI at 3 tesla

Assessment of vascular properties is essential to diagnosis and follow‐up and basic understanding of pathogenesis in brain tumors. In this study, a procedure is presented that allows concurrent estimation of cerebral perfusion, blood volume, and blood‐brain permeability from dynamic T₁‐weighted imaging of a bolus of a paramagnetic contrast agent passing through the brain. The methods are applied in patients with brain tumors and in healthy subjects. Perfusion was estimated by model‐free deconvolution using Tikhonov's method (gray matter/white matter/tumor: 72 ± 16/30 ± 8/56 ± 45 mL/100 g/min); blood volume (6 ± 2/4 ± 1/7 ± 6 mL/100 g) and permeability (0.9 ± 0.4/0.8 ± 0.3/3 ± 5 mL/100 g/min) were estimated by using Patlak's method and a two‐compartment model. A corroboration of these results was achieved by using model simulation. In addition, it was possible to generate maps on a pixel‐by‐pixel basis of cerebral perfusion, cerebral blood volume, and blood‐brain barrier permeability. Magn Reson Med, 2009. © 2009 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.