A new method has been developed for fast image-based measurements of the transmitted radiofrequency (RF) field. The method employs an actual flip-angle imaging (AFI) pulse sequence that consists of two identical RF pulses followed by two delays of different duration (TR 1 < TR 2 ). After each pulse, a gradient-echo (GRE) signal is acquired. It has been shown theoretically and experimentally that if delays TR 1 and TR 2 are sufficiently short and the transverse magnetization is completely spoiled, the ratio r ‫؍‬ S 2 /S 1 of signal intensities S 1 and S 2 , acquired at the beginning of the time intervals TR 1 and TR 2 , depends on the flip angle (FA) of applied pulses as r ‫؍‬ (1 ؉ n * cos(FA))/(n ؉ cos(FA)), where n ‫؍‬ TR 2 /TR 1 . The method allows fast 3D implementation and provides accurate B 1 measurements that are highly insensitive to T 1 . The unique feature of the AFI method is that it uses a pulsed steady-state signal acquisition. This overcomes the limitation of previous methods that required long relaxation delays between sequence repetitions. Knowledge of the spatial distribution of the transmitted radiofrequency (RF) field is needed for a number of MR research and engineering applications, such as correcting the results of various quantitative methods, validating theoretical models for electromagnetic field calculations, ensuring quality control of RF coils, and testing the MR compatibility of implanted objects, especially at high magnetic fields. While the RF field distribution can be obtained with the use of a small pickup coil or phantom measurements, direct in vivo B 1 mapping in the human body is always preferable, particularly for correcting patient-specific quantitative data, where individual variations in the B 1 field generally depend on the coil position, the dielectric properties of the tissues, and the subject's size. Although a number of methods have been proposed for image-based RF field measurements (1-17), many of them are difficult or impossible to use in vivo because they require serial scans at a variable transmitter power or pulse duration (1-7), have a high sensitivity to static magnetic field inhomogeneity (8,9), and result in high RF power deposition (1,3). These difficulties have been overcome by several B 1 mapping techniques that are more suitable for in vivo applications (10 -17); however, further improvements in time efficiency, anatomical coverage, and accuracy are needed to introduce B 1 mapping into routine practice.A common method for B 1 mapping is based on two scans acquired with a spin-echo (SE) or gradient-echo (GRE) imaging sequence at two nominal flip angles (FAs, usually ␣ and 2␣) chosen in a range of optimal sensitivities to B 1 variations for a particular sequence (10). To avoid the dependence of the signal on T 1 , the repetition time (TR) of the sequence should be sufficiently long to achieve complete relaxation of magnetization (10). More time-efficient variants of the double-angle method (11-15) include driven recovery (11) or presaturation (15) of magne...

Objective-This study evaluates the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo. Methods and Results-Thirty-one subjects scheduled for carotid endarterectomy were imaged with a 1.5T scanner using time-of-flight-, T1-, proton density-, and T2-weighted images. A total of 214 MR imaging locations were matched to corresponding histology sections. For MRI and histology, area measurements of the major plaque components such as lipid-rich/necrotic core (LR/NC), calcification, loose matrix, and dense (fibrous) tissue were recorded as percentages of the total wall area. Intraclass correlation coefficients (ICCs) were computed to determine intrareader and inter-reader reproducibility. Key Words: atherosclerosis Ⅲ magnetic resonance imaging Ⅲ carotid artery Ⅲ plaque A therosclerosis and its thrombotic complications are the leading cause of morbidity and mortality in industrialized countries. Therefore, the need for new medical therapies and technology to treat and prevent cardiovascular atherosclerotic disease is enormous.Accurate information of atherosclerotic plaque morphology and plaque composition is necessary to identify the "vulnerable plaques" that are likely to cause embolic events. A noninvasive imaging modality that could provide such information would be an invaluable tool in studies of the relationship between plaque composition/morphology and plaque progression/regression. Furthermore, such imaging techniques may be used in clinical trials to monitor the effects of drugs on diseased arteries.B-Mode ultrasonography has been used widely in plaque progression/regression trials that involve either lipidlowering drugs or calcium channel blockers. 1 However, this modality is highly operator dependent, has limited soft tissue contrast, and requires a large number of subjects to detect a significant change in the intima-media thickness. 1 Intravascular ultrasound (IVUS) is used increasingly in atherosclerosis regression/progression trials that study coronary arteries. 2 Although IVUS is highly reproducible 3 and provides tomographic information about the vessel wall, 3 it is an invasive procedure and has limited capacity to discriminate between fibrous and fatty plaques. 4 Recent publications 5-11 have shown that in vivo MRI can identify the main components of the atherosclerotic plaque such as the lipid-rich/necrotic core (LR/NC), calcification, and hemorrhage. In addition, morphological information about the status of the fibrous cap 12 and the American Heart Association (AHA) lesion type 13 can be obtained noninvasively. Moreover, the tomographic orientation of MRI enables the full cross-sectional view of the vessel wall, which can be measured accurately 14 and reproducibly. 15 It has been demonstrated that ex vivo MRI of endarterectomy specimen is able to identify 16 and quantify 17,18 plaque components with high diagnostic accuracy. This study is aimed at evaluating the ability of MRI to quantify all major carotid atherosclerotic plaque components in vivo, using histolog...

A new method was developed for fast quantitative mapping of the macromolecular proton fraction (MPF) defined within the two-pool model of magnetization transfer (MT). The method utilizes a single image with off-resonance saturation, a reference image for data normalization, and T1, B0, and B1 maps with the total acquisition time ~10 min for whole-brain imaging. MPF maps are reconstructed by iterative solution of the matrix pulsed MT equation with constrained values of other model parameters. Theoretical error model describing the variance due to noise and the bias due to deviations of constrained parameters from their actual values was formulated based on error propagation rules. The method was validated by comparison with the conventional multi-parameter multi-point fit of the pulsed MT model based on data from two healthy subjects and two multiple sclerosis patients. It was demonstrated theoretically and experimentally that accuracy of the method depends on the offset frequency and flip angle of the saturation pulse, and optimal ranges of these parameters are 4-7 kHz and 600-900°, respectively. At optimal sampling conditions, the single-point method enables <10% relative MPF errors. Comparison with the multi-parameter fitting method revealed very good agreement with no significant bias and limits of agreement around ±0.7%.

A new method of pulsed Z-spectroscopic imaging is proposed for in vivo visualization and quantification of the parameters describing cross-relaxation between protons with liquid-like and solid-like relaxation properties in tissues. The method is based on analysis of the magnetization transfer (MT) effect as a function of the offset frequency and amplitude of a pulsed off-resonance saturation incorporated in a spoiled gradientecho MRI pulse sequence. The theoretical concept of the method relies on an approximated analytical model of pulsed MT that provides a simple three-parameter equation for a pulsed steady-state Z-spectrum taken far from resonance. Using this model, the parametric images of cross-relaxation rate constant, content, and T 2 of the semisolid proton fraction can be reconstructed from a series of MT-weighted images and a coregistered T 1 map. The method was implemented on a 0. Cross-relaxation is known as an underlying mechanism of the magnetization transfer (MT) effect in biological systems, which is described traditionally by a two-pool (binary-spin-bath) model (1-8) including two types of protons with different mobility: free (liquid) and bound with biopolymers (semisolid). Within this model, a quantitative description of magnetization dynamics is determined by both the intrinsic relaxation properties of pools and the parameters specifically related to cross-relaxation, such as the rate constant and the content of the semisolid fraction. While the MT effect is widely exploited in MRI on an empirical level (2,3,9), meaningful clinical applications of MT methods require knowledge of the cross-relaxation parameters for a variety of normal and pathologic tissues in vivo. Such information is essential for both the proper design of MT MRI protocols (10) and the biophysically consistent interpretation of results. To date, progress in this area has been limited by the absence of adequate methods for cross-relaxation measurements in human MRI. Although several attempts to develop such techniques have been reported (11)(12)(13)(14), none of them are suitable for extensive clinical application.Generally, existing NMR methods (both imaging and non-imaging) for quantitative studies of cross-relaxation in biologic materials can be classified by their technical principles into two groups: on-resonance cross-relaxometry (1,8,11,12) and cross-relaxation spectroscopy (or Z-spectroscopy) (4 -7,13-16). The first group relies on a semiselective inversion of free spins (1,8,12) or a binomial pulsed excitation of bound fraction (8,11) followed by an analysis of a time-dependent response. However, by taking advantage of short RF pulses these techniques suffer from a relatively low accuracy and lack of information about the spectral characteristics of the semisolid pool. Two crossrelaxometric methods have been proposed for MRI applications (11,12). Chai et al. (11) attempted to quantify all parameters of the two-pool model in a human brain in vivo using a train of binomial pulses with variable length. An extremely long ...

Background and Purpose-High-resolution, multicontrast magnetic resonance imaging (MRI) has developed into an effective tool for the identification of carotid atherosclerotic plaque components, such as necrotic core, fibrous matrix, and hemorrhage/thrombus. Factors that may lead to plaque instability are lipid content, thin fibrous cap, and intraplaque hemorrhage. Determining the age of intraplaque hemorrhage can give insight to the history and current condition of the biologically active plaque. The aim of this study was to develop criteria for the identification of the stages of intraplaque hemorrhage using high-resolution MRI. Methods-Twenty-seven patients, scheduled for carotid endarterectomy (CEA), were imaged on a 1.5-T GE SIGNA scanner (sequences: 3-dimensional time of flight, double-inversion recovery, T1-weighted (T1W), PDW and T2W). Two readers, blinded to histology, reviewed MR images and grouped hemorrhage into fresh, recent, and old categories using a modified cerebral hemorrhage criteria. The CEA specimens were serially sectioned and graded as to presence and stage of hemorrhage. Results-Hemorrhage was histologically identified and staged in 145/189 (77%) of carotid artery plaque locations. MRI detected intraplaque hemorrhage with high sensitivity (90%) but moderate specificity (74%). Moderate agreement in classifying stages occurred between MRI and histology (Cohen ϭ0.7, 95% CI: 0.5 to 0.8 for reviewer 1 and 0.4, 95% CI: 0.2 to 0.6 for reviewer 2), with moderate agreement between the 2 MRI readers (ϭ0.4, 95% CI: 0.3 to 0.6). Conclusion-Multicontrast MRI can detect and classify carotid intraplaque hemorrhage with high sensitivity and moderate specificity.

Variable flip angle T 1 mapping and actual flip-angle imaging B 1 mapping are widely used quantitative MRI methods employing radiofrequency spoiled gradient-echo pulse sequences. Incomplete elimination of the transverse magnetization in these sequences has been found to be a critical source of T 1 and B 1 measurement errors. In this study, comprehensive theoretical analysis of spoiling-related errors in variable flip angle and actual flip-angle imaging methods was performed using the combined isochromat summation and diffusion propagator model and validated by phantom experiments. The key theoretical conclusion is that correct interpretation of spoiling phenomena in fast gradient-echo sequences requires accurate consideration of the diffusion effect. A general strategy for improvement of T 1 and B 1 measurement accuracy was proposed based on the strong spoiling regimen, where diffusion-modulated spatial averaging of isochromats becomes a dominant factor determining magnetization evolution. Practical implementation of strongly spoiled variable flip angle and actual flip-angle imaging techniques requires sufficiently large spoiling gradient areas (A G ) in combination with optimal radiofrequency phase increments (f 0 ). Optimal regimens providing <2% relative T 1 and B 1 measurement errors in a variety of tissues were theoretically derived for prospective in vivo variable flip angle (pulse repetition time 5 (1) is a widely used method allowing generation of T 1 -weighted contrast in gradient echo (GRE) sequences with short pulse repetition time (TR). Technically, RF spoiling is achieved by linearly incrementing the phase of an RF pulse between successive TR with a specific value of the phase increment. After the initial publication (1) suggested optimal phase increments of 117 or 123 , several other values were proposed (2-4). Default settings of the RF phase increment also vary between MRI equipment manufacturers (5). While all these approaches generally allow acquisition of heavily T 1 -weighted GRE images in the steady state, special attention should be given to the role of RF spoiling in quantitative imaging methods.One of most widely used quantitative applications of the RF spoiled GRE sequence is the variable flip angle (VFA) method for T 1 mapping (6,7). In modern implementations, the VFA method takes advantage of a very short TR achievable due to RF spoiling, which allows time-efficient three-dimensional implementation with large anatomic coverage (8-10). Accuracy of VFA T 1 measurements was extensively studied in aspects of optimal flip-angle sampling (7-10) and correction of amplitude of RF field (B 1 ) nonuniformities (4,9,10). Recently, incomplete spoiling was identified as a critical source of errors in the VFA method (4,5,11). While data processing in this method relies on the ideally spoiled signal equation (12), the use of fast RF spoiled sequences may result in partial preservation of transverse coherences and, therefore, deviation of the signal behavior from the idealized theoretical model. Techn...

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Cross-relaxation imaging (CRI) is a quantitative magnetic resonance technique that measures the kinetic parameters of magnetization transfer between protons bound to water and protons bound to macromolecules. In this study, in vivo, four-parameter CRI of normal rat brains (N=5) at 3.0 T was first directly compared to histology. The bound pool fraction, f, was strongly associated with myelin density (Pearson's r = 0.99, p <0.001). The correlation persisted in separate analyses of gray matter (GM; r = 0.89, p =0.046) and white matter (WM; r = 0.97, p =0.029). Subsequently, a new time-efficient approach for solely capturing the whole-brain parametric map of f was proposed, validated with histology, and used to estimate myelin density. Since the described approach for the rapid acquisition of f applied constraints to other CRI parameters, a theoretical analysis of error was performed. Estimates of f in normal and pathologic tissue were expected to have <10% error. A comparison of values for f obtained from the traditional four-parameter fit of CRI data versus the proposed rapid acquisition of f was within this expected margin for in vivo rat brain gliomas (N=4; mean ± SE; 3.9 ± 0.2% vs. 4.0 ± 0.2%, respectively). In both whole-brain f maps and myelin density maps, replacement of normal GM and WM by proliferating and invading tumor cells could be readily identified. The rapid, whole-brain acquisition of the bound pool fraction may provide a reliable method for detection of glioma invasion in both GM and WM during animal and human imaging.