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Quantitative magnetization transfer imaging using balanced SSFP. Magn Reson Med

Department of Radiology, Division of Radiological Physics, University Hospital Basel, Basel, Switzerland.
Magnetic Resonance in Medicine (Impact Factor: 3.4). 09/2008; 60(3):691-700. DOI: 10.1002/mrm.21705
Source: PubMed

ABSTRACT It is generally accepted that signal formation in balanced steady-state free precession (bSSFP) is a simple function of relaxation times and flip angle only. This can be confirmed for fluids, but for more complex substances, magnetization transfer (MT) can lead to a considerable loss of steady-state signal. Thus, especially in tissues, the analytical description of bSSFP requires a revision to fully take observed effects into account. In the first part of this work, an extended bSSFP signal equation is derived based on a binary spin-bath model. Based on this new model of bSSFP signal formation, quantitative MT parameters such as the fractional pool size, corresponding magnetization exchange rates, and relaxation times can be explored. In the second part of this work, model parameters are derived in normal appearing human brain. Factors that may influence the quality of the model, such as B(1) field inhomogeneities or off-resonances, are discussed. Overall, good correspondence between parameters derived from two-pool bSSFP and common quantitative MT models is observed. Short repetition times in combination with high signal-to-noise ratios make bSSFP an ideal candidate for the acquisition of high resolution isotropic quantitative MT maps, as for the human brain, within clinically feasible acquisition times.

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    • "The number of total images required can be reduced by designing optimal sampling strategies (Cercignani and Alexander, 2006; Levesque et al., 2011) or by fixing certain model parameters in the fitting procedure (Underhill et al., 2009, 2011). Potentially more efficient strategies based upon steady-state free-precession (SSFP) sequences (Garcia et al., 2010; Gloor et al., 2008) may also be employed. As an alternative, or perhaps in combination with these strategies, one could translate qMT imaging approaches to higher field strengths. "
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    ABSTRACT: Quantitative magnetization transfer (qMT) imaging yields indices describing the interactions between free water protons and immobile macromolecular protons. These indices include the macromolecular to free pool size ratio (PSR), which has been shown to be correlated with myelin content in white matter. Because of the long scan times required for whole-brain imaging (≈20-30min), qMT studies of the human brain have not found widespread application. Herein, we investigated whether the increased signal-to-noise ratio available at 7.0T could be used to reduce qMT scan times. More specifically, we developed a selective inversion recovery (SIR) qMT imaging protocol with a i) novel transmit radiofrequency (B(1)(+)) and static field (B(0)) insensitive inversion pulse, ii) turbo field-echo readout, and iii) reduced TR. In vivo qMT data were obtained in the brains of healthy volunteers at 7.0T using the resulting protocol (scan time≈40s/slice, resolution=2×2×3mm(3)). Reliability was also assessed in repeated acquisitions. The results of this study demonstrate that SIR qMT imaging can be reliably performed within the radiofrequency power restrictions present at 7.0T, even in the presence of large B(1)(+) and B(0) inhomogeneities. Consistent with qMT studies at lower field strengths, the observed PSR values were higher in white matter (mean±SD=17.6±1.3%) relative to gray matter (10.3±1.6%) at 7.0T. In addition, regional variations in PSR were observed in white matter. Together, these results suggest that qMT measurements are feasible at 7.0T and may eventually allow for the high-resolution assessment of changes in composition throughout the normal and diseased human brain in vivo.
    NeuroImage 08/2012; 64C(1):640-649. DOI:10.1016/j.neuroimage.2012.08.047 · 6.36 Impact Factor
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    • "We addressed this issue by adjusting all the analysis for GM local volume through the BPM tool. Nevertheless, for future studies, it might be desirable to use different acquisition approaches, such as those based on balanced steady state free precession (bSSFP) (Bieri and Scheffler, 2006, 2007; Gloor et al., 2008), which gives better SNR and therefore allows higher resolution to be achieved. A related issue is that of scan time, which is still fairly long (25 min for the qMT only) for a typical clinical setting. "
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    ABSTRACT: Preliminary studies, based on a region-of-interest approach, suggest that quantitative magnetization transfer (qMT), an extension of magnetization transfer imaging, provides complementary information to conventional magnetic resonance imaging (MRI) in the characterisation of Alzheimer's disease (AD). The aim of this study was to extend these findings to the whole brain, using a voxel-wise approach. We recruited 19AD patients and 11 healthy subjects (HS). All subjects had an MRI acquisition at 3.0T including a T(1)-weighted volume, 12 MT-weighted volumes for qMT, and data for computing T(1) and B(1) maps. The T(1)-weighted volumes were processed to yield grey matter (GM) volumetric maps, while the other sequences were used to compute qMT parametric maps of the whole brain. qMT maps were warped to standard space and smoothed, and subsequently compared between groups. Of all the qMT parameters considered, only the forward exchange rate, RM(0)(B), showed significant group differences. These images were therefore retained for the multimodal statistical analysis, designed to locate brain regions of RM(0)(B) differences between AD and HS groups, adjusting for local GM atrophy. Widespread areas of reduced RM(0)(B) were found in AD patients, mainly located in the hippocampus, in the temporal lobe, in the posterior cingulate and in the parietal cortex. These results indicate that, among qMT parameters, RM(0)(B) is the most sensitive to AD pathology. This quantity is altered in the hippocampus of patients with AD (as found by previous works) but also in other brain areas, that PET studies have highlighted as involved with both, reduced glucose metabolism and amyloid β deposition. RM(0)(B) might reflect, through the measurement of the efficiency of MT exchange, some information with a specific pathological counterpart. Given previous evidence of a strict relationship between RM(0)(B) and intracellular pH, an intriguing speculation is that our findings might reflect metabolic changes related to mitochondrial dysfunction, which has been proposed as a contributor to neurodegeneration in AD.
    NeuroImage 01/2012; 59(2):1114-22. DOI:10.1016/j.neuroimage.2011.09.043 · 6.36 Impact Factor
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    ABSTRACT: The primary aim of this thesis is the reconciliation of two seemingly disparate quantitative magnetic resonance imaging (MRI) techniques proposed to characterize human brain white matter (WM) in health and disease. Quantitative magnetization transfer imaging (QMTI) and multi-component analysis of T2 relaxation (QT2) both attempt to quantify myelin content in vivo, but are based on fundamentally different models of WM. QMTI probes the macromolecular component of tissue using a two-pool model of magnetization transfer, while QT2 isolates the water signal from distinct micro-anatomical compartments. The specific objectives were to determine the interrelationship between measurements made with both techniques in the context of potential pathological changes associated with multiple sclerosis (MS), and to apply both to track WM changes in the acute phase of MS lesions. First, simulations were used to evaluate the theoretical sensitivity of each technique to the characteristics of a model of WM that incorporates four pools of magnetization, based on published in vitro measurements. Next, the experimental reproducibility of each technique was investigated, and the impact of certain basic variations in the data acquisition and analysis procedures was evaluated. In the final stage, both methods were applied longitudinally in vivo to assess the dynamic changes that occur in acute, contrast-enhancing lesions of MS. The theoretical results illustrate the sensitivity and limitations of QMTI and QT2 to specific pathology-inspired modifications of WM, and shed new light on the potential specificity of often-neglected QMTI parameters. The reproducibility of both techniques is acceptable for use in repeated clinical measurements, and QMTI has lower variability overall. The importance of corrections for magnetic field inhomogeneity in QMTI is demonstrated, and a simple optimization of the QMTI data acquisition is introduced. Both techniques were sensitive to active disease pathology in the longitudinal study of MS patients. Overall, this thesis demonstrates the complementary nature and usefulness of QMTI and QT2 in the characterization of the natural disease course of a degenerative disease of the human central nervous system. With further refinement, these techniques could play an important role in the study of other diseases, and have the potential to serve as outcome measures in clinical trials. L'objectif principal de cette thèse est la réconciliation de deux techniques quantitatives d'imagerie par résonance magnétique, en apparence difféerentes, utilisées pour la caractérisation de la susbtance blanche du cerveau humain en santé ou affectée par la maladie. Les techniques d'imagerie quantitative par transfert de magnétisation (QTM) et d'analyse de la relaxation T2 par de multiples composantes (QT2) proposent toutes deux des mesures in vivo de la quantitée de myéline, mais à l'aide de modèles fondamentalement différents. D'un côté, l'imagerie QTM sonde la composante macro-moléculaire des tissues à l'aide d'un modèle à deux réservoirs pour le transfert de magnétisation. De l'autre, l'imagerie QT2 sépare les signaux acqueux provenant de compartiments micro-anatomiques distincts. Plus spécifiquement, cet ouvrage cherche à mieux comprendre l'interdépendance des mesures de ces deux techniques dans le contexte pathologique de la sclérose en plaques (SEP), pour ensuite les appliquer à l' étude de lésions aigues de SEP. En premier lieu, des simulations ont été effectuées pour évaluer la sensibilité de chaque technique aux caractéristiques d'un modèle plus complet de la substance blanche, qui découle de résultats in vitro publiés et incorpore quatre réservoirs de magnétisation. Ensuite, la reproductibilité de chacune des techniques a été évaluée; de plus, quelques variations élémentaires des méthodes d'acquisition et d'analyse des données examinées. En dernier lieu, les deux techniques ont été utilisées in vivo afin de mesurer les changements dynamiques des lésions aigues de SEP, présentant un hyper-signal rehaussée par un agent de contraste. Les résultats des simulations démontrent d'un point de vue théorique la sensibilité et les limites de chacune de ces technique aux changements dans la substance blanche. Ces résultats apportent également de nouvelles connaissances sur le rôle potentiel que peuvent jouer certains paramètres souvent négligés de l'imagerie QTM. La reproductibilité acceptable de ces techniques ouvre la voie à leur utilisation répétée en recherche clinique, en sachant que l'imagerie QTM est généralement la moins variable. L'importance des corrections des inhomogénéités de champs magnétiques pour l'imagerie QTM a été démontrée, et une technique simple d'optimisation d'acquisition des données d'imagerie QTM a été présentée. Cette thèse démontre la complémentarité et l'utilité des méthodes d'imagerie QTM et QT2 dans la caractérisation de l'évolution d'une maladie dégénérative du système nerveux central humain. Suivant leur amélioration, ces techniques joueront des rôles importants dans l'étude d'autres maladies du système nerveux central, et pourraient servir d'outil de mesure lors d'essais cliniques.
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