Optimal acquisition schemes for in vivo quantitative magnetization transfer MRI.

This paper uses the theory of Cramer-Rao lower bounds (CRLB) to obtain optimal acquisition schemes for in vivo quantitative magnetization transfer (MT) imaging, although the method is generally applicable to any multiparametric MRI technique. Quantitative MT fits a two-pool model to data collected at different sampling points or settings of amplitude and offset frequency in the MT saturation pulses. Here we use simple objective functions based on the CRLB to optimize sampling strategies for multiple parameters simultaneously, and use simulated annealing to minimize these objective functions with respect to the sampling configuration. Experiments compare optimal schemes derived for quantitative MT in the human white matter (WM) at 1.5T with previously published schemes using both synthetic and human-brain data. Results show large reductions in error of the fitted parameters with the new schemes, which greatly increases the clinical potential of in vivo quantitative MT. Since the sampling-scheme optimization requires specific settings of the MT parameters, we also show that the optimum schemes are robust to these settings within the range of MT parameters observed in the brain.     

Regional variations in normal brain shown by quantitative magnetization transfer imaging.

A quantitative magnetization transfer imaging (qMTI) study, based on a two-pool model of magnetization transfer, was performed on seven normal subjects to determine, on a regional basis, normal values for the pool sizes, exchange, and relaxation parameters that characterize the MT phenomenon. Regions were identified on high-resolution anatomical scans using a combination of manual and automatic methods. Only voxels identified as pure tissue at the resolution of the quantitative scans were considered for analysis. While no left/right differences were observed, significant differences were found among white-matter regions and gray-matter regions. These regional differences were compared with existing cytoarchitectural data. In addition, the pattern and magnitude of the regional differences observed in white matter was found to be different from that reported previously for an alternative putative MRI measure of myelination, the 10-50-ms T2 component described as myelin water.     

Quantitation and localization of blood-to-brain influx by magnetic resonance imaging and quantitative autoradiography in a model of transient focal ischemia.

The ability of gadolinium-diethylenetriaminepentaacetic acid (Gd-DTPA) enhanced MRI to localize and quantitate blood-brain barrier (BBB) opening was evaluated against quantitative autoradiographic (QAR) imaging of (14)C-alpha-aminoisobutyric acid (AIB) distribution. The blood-to-brain transfer constant (K(i)) for Gd-DTPA was determined by MRI in rats after 3 h of focal cerebral ischemia plus 2.5 h of reperfusion (n = 9), and that of AIB was determined by QAR shortly thereafter. Tissue regions of interest (ROIs) for Gd-DTPA leakage were identified by ISODATA segmentation of pre- and post-Gd-DTPA Look-Locker (L-L) T(1) maps. Patlak plots were constructed using time course of blood and tissue T(1) changes induced by Gd for estimating K(i). Among the nine rats, 14 sizable regions of AIB uptake were found; 13 were also identified by ISODATA segmentation. Although the 13 MRI-ROIs spatially approximated those of AIB uptake, the segmentation sometimes missed small areas of lesser AIB uptake that did not extend through more than 60% of the 2.0-mm-thick slice. Mean K(i)'s of AIB were highly correlated with those of Gd-DTPA across the 13 regions; the group means (+/-SD) were similar for the two tracers (7.1 +/- 3.3 x 10(-3) and 6.8 +/- 3.5 x 10(-3) ml.g(-1) . min(-1), respectively). In most instances, Gd-DTPA MRI accurately localized areas of BBB opening.     

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 imaging of magnetization transfer exchange and relaxation properties in vivo using MRI.

We describe a novel imaging technique that yields all of the observable properties of the binary spin-bath model for magnetization transfer (MT) and demonstrate this method for in vivo studies of the human head. Based on a new model of the steady-state behavior of the magnetization during a pulsed MT-weighted imaging sequence, this approach yields parametric images of the fractional size of the restricted pool, the magnetization exchange rate, the T(2) of the restricted pool, as well as the relaxation times in the free pool. Validated experimentally on agar gels and samples of uncooked beef, we demonstrate the method's application on two normal subjects and a patient with multiple sclerosis.     

Incidental magnetization transfer contrast by fat saturation preparation pulses in multislice look‐locker echo planar imaging

In this study, it is demonstrated that fat saturation (FS) preparation (prep) pulses generate incidental magnetization transfer contrast (MTC) in multislice Look‐Locker (LL) imaging. It is shown that frequency‐selective FS prep pulses can invoke MTC through the exchange between free and motion‐restricted protons. Simulation reveals that the fractional signal loss by these MTC effects is more severe for smaller flip angles (FAs), shorter repetition times (TRs), and greater number of slices (SN). These incidental MTC effects result in a signal attenuation at a steady state (up to 30%) and a T₁ measurement bias (up to 20%) when using inversion recovery (IR) LL echo‐planar imaging (EPI) sequences. Furthermore, it is shown that water‐selective MRI using binomial pulses has the potential to minimize the signal attenuation and provide unbiased T₁ measurement without fat artifacts in MR images. Magn Reson Med, 2009. © 2009 Wiley‐Liss, Inc.     

Quantifying exchange rates in chemical exchange saturation transfer agents using the saturation time and saturation power dependencies of the magnetization transfer effect on the magnetic resonance imaging signal (QUEST and QUESP): Ph calibration for poly-L-lysine and a starburst dendrimer.

The ability to measure proton exchange rates in tissue using MRI would be very useful for quantitative assessment of magnetization transfer properties, both in conventional MT imaging and in the more recent chemical exchange saturation transfer (CEST) approach. CEST is a new MR contrast mechanism that depends on several factors, including the exchange rate of labile protons in the agent in a pH-dependent manner. Two new methods to monitor local exchange rate based on CEST are introduced. The two MRI-compatible approaches to measure exchange are quantifying exchange using saturation time (QUEST) dependence and quantifying exchange using saturation power (QUESP) dependence. These techniques were applied to poly-L-lysine (PLL) and a generation-5 polyamidoamine dendrimer (SPD-5) to measure the pH dependence of amide proton exchange rates in the physiologic range. Data were fit both to an analytical expression and to numerical solutions to the Bloch equations. Results were validated by comparison with exchange rates determined by two established spectroscopic methods. The exchange rates determined using the four methods were pooled for the pH-calibration curve of the agents consisting of contributions from spontaneous (k0) acid catalyzed (ka), and base catalyzed (kb) exchange rate constants. These constants were k0 = 68.9 Hz, ka = 1.21 Hz, kb = 1.92 x 10(9) Hz, and k0 = 106.4 Hz, ka = 25.8 Hz, kb = 5.45 x 10(8) Hz for PLL and SPD-5, respectively, showing the expected predominance of base-catalyzed exchange for these amide protons.     

Correction for artifacts induced by B(0) and B(1) field inhomogeneities in pH-sensitive chemical exchange saturation transfer (CEST) imaging.

Chemical exchange saturation transfer (CEST) imaging provides an indirect detection mechanism that allows quantification of certain labile groups unobservable using conventional MRI. Recently, amide proton transfer (APT) imaging, a variant form of CEST imaging, has been shown capable of detecting lactic acidosis during acute ischemia, providing information complementary to that of perfusion and diffusion MRI. However, CEST contrast is usually small, and therefore, it is important to optimize experimental conditions for reliable and quantitative CEST imaging. In particular, CEST imaging is sensitive to B(0) and B(1) field, while on the other hand; field inhomogeneities persist despite recent advances in magnet technologies, especially for in vivo imaging at high fields. Consequently, correction algorithms that can compensate for field inhomogeneity-induced measurement errors in CEST imaging might be very useful. In this study, the dependence of CEST contrast on field distribution was solved and a correction algorithm was developed to compensate for field inhomogeneity-induced CEST imaging artifacts. In addition, the proposed algorithm was verified with both numerical simulation and experimental measurements, and showed nearly complete correction of CEST imaging measurement errors caused by moderate field inhomogeneity.     

Acute cerebral ischemia in rats studied by Carr-Purcell spin-echo magnetic resonance imaging: assessment of blood oxygenation level-dependent and tissue effects on the transverse relaxation.

Acute cerebral ischemia has been shown to be associated with an enhanced transverse relaxation rate in rat brain parenchyma, chiefly due to the blood oxygenation level-dependent (BOLD) effect. In this study, Carr-Purcell R(2) (CP R(2)), acquired both with short and long time intervals between centers of adiabatic pi-pulses (tau(CP)), was used to assess the contributions of BOLD and tissue effects to the transverse relaxation in two brain ischemia models of rat at 4.7 T. R(1rho) and diffusion MR images were also acquired in the same animals. During the first minutes of global ischemia, the long tau(CP) R(2) in brain parenchyma increased, whereas the short tau(CP) R(2) was unchanged. Based on the simulations, and using constraints of intravascular BOLD effect on parenchymal R(2), the former observation was ascribed to be due to susceptibility changes arising in the extravascular compartment. R(1rho) declined almost immediately after the onset of focal cerebral ischemia, and further declined during the evolution of ischemic damage. Interestingly, short tau(CP) CP R(2) started to decline after some 20 min of focal ischemia and declined over a time course similar to that of R(1rho), indicating that it may be an MRI marker for irreversible tissue changes in cerebral ischemia. The present results show that CP R(2) MRI can reveal both tissue- and blood-derived contrast changes in acute cerebral ischemia.