Ives R Levesque

Stanford University, Palo Alto, California, United States

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Publications (19)60.87 Total impact

  • Eva Alonso‐Ortiz, Ives R. Levesque, G. Bruce Pike
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    ABSTRACT: Multiexponential T2 relaxation time measurement in the central nervous system shows a component that originates from water trapped between the lipid bilayers of myelin. This myelin water component is of significant interest as it provides a myelin-specific MRI signal of value in assessing myelin changes in cerebral white matter in vivo. In this article, the various acquisition and analysis strategies proposed to date for myelin water imaging are reviewed and research conducted into their validity and clinical applicability is presented. Comparisons between the imaging methods are made with a discussion regarding potential difficulties and model limitations. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 03/2014; · 3.27 Impact Factor
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    ABSTRACT: There are many T1 mapping methods available, each of them validated in phantoms and reporting excellent agreement with literature. However, values in literature vary greatly, with T1 in white matter ranging from 690 to 1100 ms at 3 Tesla. This brings into question the accuracy of one of the most fundamental measurements in quantitative MRI. Our goal was to explain these variations and look into ways of mitigating them. We evaluated the three most common T1 mapping methods (inversion recovery, Look-Locker, and variable flip angle) through Bloch simulations, a white matter phantom and the brains of 10 healthy subjects (single-slice). We pooled the T1 histograms of the subjects to determine whether there is a sequence-dependent bias and whether it is reproducible across subjects. We found good agreement between the three methods in phantoms, but poor agreement in vivo, with the white matter T1 histogram peak in healthy subjects varying by more than 30% depending on the method used. We also found that the pooled brain histograms displayed three distinct white matter peaks, with Look-Locker consistently underestimating, and variable flip angle overestimating the inversion recovery T1 values. The Bloch simulations indicated that incomplete spoiling and inaccurate B1 mapping could account for the observed differences. We conclude that the three most common T1 mapping protocols produce stable T1 values in phantoms, but not in vivo. To improve the accuracy of T1 mapping, we recommend that sites perform in vivo validation of their T1 mapping method against the inversion recovery reference method, as the first step toward developing a robust calibration scheme. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 02/2014; · 3.27 Impact Factor
  • Tao Zhang, John M Pauly, Ives R Levesque
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    ABSTRACT: To accelerate MR parameter mapping using a locally low rank (LLR) constraint, and the combination of parallel imaging and the LLR constraint. An LLR method is developed for MR parameter mapping and compared with a globally low rank method in a multiecho spin-echo T2 mapping experiment. For acquisition with coil arrays, a combined LLR and parallel imaging method is proposed. The proposed method is evaluated in a variable flip angle T1 mapping experiment and compared with the LLR method and parallel imaging alone. In the multiecho spin-echo T2 mapping experiment, the LLR method is more accurate than the globally low rank method for acceleration factors 2 and 3, especially for tissues with high T2 values. Variable flip angle T1 mapping is achieved by acquiring datasets with 10 flip angles, each dataset accelerated by a factor of 6, and reconstructed by the proposed method with a small normalized root mean square error of 0.025. The LLR method is likely superior to the globally low rank method for MR parameter mapping. The proposed combined LLR and parallel imaging method has better performance than the two methods alone, especially with highly accelerated acquisition. Magn Reson Med, 2014. © 2014 Wiley Periodicals, Inc.
    Magnetic Resonance in Medicine 02/2014; · 3.27 Impact Factor
  • Journal of Neuroradiology. 01/2014; 41(1):12.
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    ABSTRACT: Novel MR image acquisition strategies have been investigated to elicit contrast within the thalamus, but direct visualization of individual thalamic nuclei remains a challenge because of their small size and the low intrinsic contrast between adjacent nuclei. We present a step-by-step specific optimization of the 3D MPRAGE pulse sequence at 7T to visualize the intra-thalamic nuclei. We first measured T1 values within different sub-regions of the thalamus at 7T in 5 individuals. We used these to perform simulations and sequential experimental measurements (n=17) to tune the parameters of the MPRAGE sequence. The optimal set of parameters was used to collect high-quality data in 6 additional volunteers. Delineation of thalamic nuclei was performed twice by one rater and MR-defined nuclei were compared to the classic Morel histological atlas. T1 values within the thalamus ranged from 1400ms to 1800ms for adjacent nuclei. Using these values for theoretical evaluations combined with in vivo measurements, we showed that a short inversion time (TI) close to the white matter null regime (TI=670ms) enhanced the contrast between the thalamus and the surrounding tissues, and best revealed intra-thalamic contrast. At this particular nulling regime, lengthening the time between successive inversion pulses (TS=6000ms) increased the thalamic signal and contrast and lengthening the α pulse train time (N*TR) further increased the thalamic signal. Finally, a low flip angle during the gradient echo acquisition (α=4°) was observed to mitigate the blur induced by the evolution of the magnetization along the α pulse train. This optimized set of parameters enabled the 3D delineation of 15 substructures in all 6 individuals; these substructures corresponded well with the known anatomical structures of the thalamus based on the classical Morel atlas. The mean Euclidean distance between the centers of mass of MR- and Morel atlas-defined nuclei was 2.67mm (±1.02mm). The reproducibility of the MR-defined nuclei was excellent with intraclass correlation coefficient measured at 0.997 and a mean Euclidean distance between corresponding centers of mass found at first versus second readings of 0.69mm (±0.38mm). This 7T strategy paves the way to better identification of thalamic nuclei for neurosurgical planning and investigation of regional changes in neurological disorders.
    NeuroImage 09/2013; · 6.25 Impact Factor
  • Ives R Levesque, John G Sled, G Bruce Pike
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    ABSTRACT: Quantitative magnetization transfer imaging (QMTI) using spoiled gradient echo sequences with pulsed off-resonance saturation can be a time-consuming technique. A method is presented for selection of an optimum experimental design for quantitative magnetization transfer imaging based on the iterative reduction of a discrete sampling of the Z-spectrum. The applicability of the technique is demonstrated for human brain white matter imaging at 1.5 T and 3 T, and optimal designs are produced to target specific model parameters. The optimal number of measurements and the signal-to-noise ratio required for stable parameter estimation are also investigated. In vivo imaging results demonstrate that this optimal design approach substantially improves parameter map quality. The iterative method presented here provides an advantage over free form optimal design methods, in that pragmatic design constraints are readily incorporated. In particular, the presented method avoids clustering and repeated measures in the final experimental design, an attractive feature for the purpose of magnetization transfer model validation. The iterative optimal design technique is general and can be applied to any method of quantitative magnetization transfer imaging.
    Magnetic Resonance in Medicine 09/2011; 66(3):635-43. · 3.27 Impact Factor
  • C. Tardif, N. Stikov, I. Levesque, B. Pike
    Proc ISMRM. 01/2011; 19:2745.
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    ABSTRACT: Quantitative magnetization-transfer imaging methods provide in vivo estimates of parameters of the two-pool model for magnetization-transfer in tissue. The goal of this study was to evaluate the reproducibility of quantitative magnetization-transfer imaging parameter estimates in healthy subjects. Magnetization-transfer-weighted and T(1) relaxometry data were acquired in five healthy subjects at multiple time points, and the variability of the resulting fitted magnetization-transfer parameters was evaluated. The impact of subsampling the magnetization-transfer data and correcting field inhomogeneities was also evaluated. The key parameters measured in this study had an average variability, across time points, of 4.7% for the relative size of the restricted pool (F), 7.3% for the forward exchange constant (k(f)), 1.9% for the free pool spin-lattice relaxation constant (R(1f)), 4.5% for the T(2) of the free pool (T(2f)), and 2.3% for the T(2) of the restricted pool (T(2r)). Our findings show that serial quantitative magnetization-transfer imaging experiments can be performed reliably, with good reproducibility of the model parameter estimates, and demonstrate the reproducibility of acquisition schemes with fewer magnetization-transfer contrasts. This establishes the feasibility of this technique for monitoring patients affected by degenerative white matter diseases while providing critical data to estimate the statistical power of such studies.
    Magnetic Resonance in Medicine 08/2010; 64(2):391-400. · 3.27 Impact Factor
  • Ives R Levesque, Charmaine L L Chia, G Bruce Pike
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    ABSTRACT: To evaluate the reproducibility of multicomponent quantitative T(2) (QT2) measurements, in particular the myelin water fraction (MWF), to determine the sensitivity of this method for monitoring myelin changes in longitudinal studies and to provide a basis for correctly powering such studies. The de facto standard 32-echo spin-echo imaging sequence was used throughout, and data were analyzed using regularized non-negative least squares (NNLS) to produce T(2) distributions. Three studies were conducted in healthy subjects. First, two acquisition protocols were compared in 10 subjects. Second, variability of QT2 was evaluated over same-day scan-rescan experiments in 6 subjects. Finally, variability was quantified in a longitudinal study of 5 subjects. A within-subject coefficient of variation (CoV) of 12% (range 4-25%) was observed for the MWF in brain white matter (WM) regions of interest (ROIs). The geometric mean T(2) was more stable, with a longitudinal CoV of 4% (range 1-6%). The choice of the geometry and repetition time of the acquisition protocol influenced the estimates of the MWF and T(2) values. The choice of integration range for the short-T(2) component had a significant effect on MWF estimates, but not on reproducibility. The reproducibility of QT2 measurements using existing methods is moderate and the method can be used in longitudinal studies, with careful consideration of the methodologic variability and an appropriate group size.
    Journal of Magnetic Resonance Imaging 07/2010; 32(1):60-8. · 2.57 Impact Factor
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    ABSTRACT: Quantitative magnetization transfer imaging provides in vivo estimates of liquid and semisolid constituents of tissue, while estimates of the liquid subpopulations, including myelin water, can be obtained from multicomponent T(2) analysis. Both methods have been suggested to provide improved myelin specificity compared to conventional MRI. The goal of this study was to investigate the sensitivity of each technique to the progression of acute, gadolinium-enhancing regions of multiple sclerosis. Magnetization transfer and T(2) relaxometry data were acquired longitudinally over the course of 1 year in five relapsing-remitting multiple sclerosis patients and in five healthy controls. Parametric maps were analyzed in enhancing lesions and normal-appearing white matter regions. Quantitative magnetization transfer parameters in lesions were most abnormal at the time of enhancement and followed a pattern of recovery over subsequent months. Lesion myelin water fraction was abnormal but did not show a significant trend over time. Quantitative magnetization transfer was able to track the degree and timing of the partial recovery in enhancing multiple sclerosis lesions in a small group of patients, while the recovery was not detected in myelin water estimates, possibly due to their large variability. Our data suggest the recovery is characterized by quick resolution of inflammation and a slower remyelination process.
    Magnetic Resonance in Medicine 02/2010; 63(3):633-40. · 3.27 Impact Factor
  • Ives R Levesque, G Bruce Pike
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    ABSTRACT: Nuclear magnetic resonance relaxation and magnetization transfer in cerebral white matter can be described using a four-pool model: two for water protons (in separate myelin and intra/extracellular compartments) and two for protons associated with the lipids and proteins of biologic membranes (of myelin and nonmyelin semisolids). This model was used to gain insight into the observations from multicomponent quantitative T(2) relaxometry and quantitative magnetization transfer imaging, both based on simplified white matter models and experimentally feasible in vivo. Using a set of coupled Bloch equations describing the behavior of the magnetization in a four-pool model of white matter, simulations of the quantitative T(2) relaxometry and quantitative magnetization transfer imaging techniques were performed. Pathology-inspired modifications were made to the four-pool model to gauge their impact on quantitative T(2) relaxometry and quantitative magnetization transfer imaging observations. Our results show that changes in the rate of water movement between microanatomic compartments may impact otherwise stable quantitative T(2) relaxometry observations; that the measure of the quantitative magnetization transfer imaging-based semisolid pool population is robust, despite the presence of two distinct semisolid components; and that quantitative magnetization transfer imaging compartment size estimates are not influenced by changes in the T(2) of the intra/extracellular water pool. The four-pool model, while impractical for in vivo characterization, yields important insight into the interpretation of changes observed with these quantitative MRI methods based on simplified models of white matter.
    Magnetic Resonance in Medicine 10/2009; 62(6):1487-96. · 3.27 Impact Factor
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    ABSTRACT: To validate the use of the magnetization transfer ratio (MTR) as a practical imaging marker of demyelination and remyelination in acute multiple sclerosis lesions. Case study. University hospital multiple sclerosis clinic. Patients Six patients with relapsing-remitting multiple sclerosis and acute gadolinium-enhancing lesions were studied serially using a quantitative magnetization transfer examination. Changes in the water content and macromolecular content, a marker of myelin content that, unlike MTR, is not affected by changes in water content (edema) associated with acute inflammation, and changes in MTR of lesions. Both the macromolecular content and MTR were lower than normal in acute lesions and recovered over several months. The decrease in macromolecular content relative to contralateral normal-appearing white matter was greater than the decrease in MTR (0.46 vs 0.75 at the time of gadolinium enhancement), likely because edema in the acute lesion increased the T1 relaxation time of water and attenuated the decrease in MTR. Nevertheless, there was still a strong correlation between changes in the relative MTR and macromolecular content (R(2) = 0.70; P < .001). Our data support the use of MTR as a practical marker of demyelination and remyelination, even in acute lesions where decreases in MTR are attenuated because of the effects of edema.
    Archives of neurology 03/2009; 66(3):375-81. · 7.58 Impact Factor
  • I.R. Levesque, G.B. Pike
    Magnetic Resonance in Medicine 01/2009; 62(6):1487-1496. · 3.27 Impact Factor
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    ABSTRACT: We assessed axonal injury and demyelination in the cerebral normal-appearing white matter (NAWM) of MS patients in a pilot study using proton magnetic resonance spectroscopic imaging and quantitative magnetization transfer (MT) imaging. Resonance intensities of N-acetylaspartate (NAA) relative to creatine (Cr) were measured in a large central brain volume. NAA/Cr in NAWM was estimated by regression of the NAA/Cr in each voxel against white matter fraction and extrapolation to a white matter fraction of 1. The fractional size of the semi-solid pool (F) was obtained from the binary spin bath model of MT by computing the model parameters from multiple MT-weighted and relaxometry acquisitions. F in NAWM was significantly smaller in the patients [0.109 (0.009)] relative to controls [0.123 (0.007), P = 0.011], but did not differ between RR [0.1085] and SP [0.1087] patients [P > 0.99]. NAA/Cr and F in the NAWM were not correlated (r = 0.16, P > 0.7), mainly due to a lack of variation in F among patients. This may indicate a floor to the extent of myelin pathology that can occur in NAWM before a lesion appears, or that axonal damage is not strictly related to demyelination. The correlation between NAWM NAA/Cr and T2w lesion volume was not significant (P > 0.1). However, dividing the lesion volumes by the mean F in T2w lesions resulted in a quantity that correlated well with NAWM NAA/Cr (r = -0.78, P = 0.038), possibly reflecting the association of Wallerian degeneration in the NAWM with axonal transection associated with demyelination within lesions.
    NeuroImage 02/2006; 29(2):637-42. · 6.25 Impact Factor
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    NeuroImage 01/2006; 29:637-642. · 6.25 Impact Factor
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    ABSTRACT: To use quantitative magnetization transfer imaging (qMTI) in an investigation of T1-weighted hypointensity observed in clinical magnetic resonance imaging (MRI) scans of multiple sclerosis (MS) patients, which has previously been proposed as a more specific indicator of tissue damage than the more commonly detected T2 hyperintensity. A cross-sectional study of 10 MS patients was performed using qMTI. A total of 60 MTI measurements were collected in each patient at a resolution of 2 x 2 x 7 mm, over a range of saturation pulses. The observed T1 and T2 were also measured. qMT model parameters were estimated using a voxel-by-voxel fit. A total of 65 T2-hyperintense lesions were identified; 53 were also T1 hypointense. In these black holes, the qMTI-derived semisolid pool fraction F correlated negatively with T(1,obs) (r2 = 0.76; P < 0.0001). The water pool absolute size (PDf) showed a weaker correlation with T(1,obs) (positive, r2 = 0.53; P < 0.0001). The magnetization transfer ratio (MTR) showed a similarly strong correlation with F and a weaker correlation with PDf (r2 = 0.18; P < 0.04). T1 increases in chronic black holes strongly correlated with the decline in semisolid pool size, and somewhat less to the confounding effect of edema. MTR was less sensitive than T(1,obs) to liquid pool changes associated with edema.
    Journal of Magnetic Resonance Imaging 03/2005; 21(2):103-10. · 2.57 Impact Factor
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    ABSTRACT: 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.
    Magnetic Resonance in Medicine 03/2004; 51(2):299-303. · 3.27 Impact Factor
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    Proceedings of the International Society for Magnetic Resonance in Medicine Tenth Scientific Meeting. 01/2002;
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    Ives Levesque
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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.

Publication Stats

181 Citations
60.87 Total Impact Points


  • 2011–2014
    • Stanford University
      • • Department of Electrical Engineering
      • • Magnetic Resonance Systems Research Laboratory
      Palo Alto, California, United States
  • 2005–2010
    • McGill University
      • McConnell Brain Imaging Centre
      Montréal, Quebec, Canada