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GIRARD Olivier

PhD - AMU Research Engineer
tel : +33 4 91 32 48 15
Key Words
- Ultra High Field MRI
- Novel Endogenous Contrast Mechanisms
- Inhomogeneous Magnetization Transfer (ihMT) MRI
- Molecular Imaging

Current Research Interest

My current research interests are focused on new endogenous contrast mechanisms and ultra-high field (UHF) MRI. UHF MRI offers unique opportunities for improved spatial resolution as well as enhanced sensitivity and contrast. Furthermore, UHR MRI require new methodological developments that drive the global MR research effort with potential outcomes benefiting to the whole MRI community. On the other hand, a variety of advanced techniques have emerged (e.g. inhomogeneous Magnetization Transfer, Arterial Spin Labeling - ASL, Quantitative Susceptibility Mapping, ultrashort TE imaging…) offering new types of contrast. These allow for a more precise and powerful tissue characterization, especially relative to tissue micro-structure and function. There is high synergy between such advanced techniques and UHF MRI. My work focus on developing new methodology to exploit them, ultimately providing new tools to push further the boundaries of what MRI can provide to researchers and clinicians.

Current Projects

- 7T MRI
- Inhomogeneous Magnetization Transfer for specific MRI of myelinated tissues
- Spinal Cord perfusion (ASL) MRI

ihMT Project - Inhomogenous Magnetization Transfer imaging

The objective of this project is the development of a new quantitative technique to assess in vivo myelin content with MRI. Despite its high clinical relevance such a tool does not exist yet. The proposed method, completely original, is based on magnetization transfer and relies on the capacity to isolate the contribution of inhomogeneously broadened components of the NMR spectrum that are usually ignored in traditionnal MT models. This technique is referred to as inhomogeneous Magnetization Transfer (ihMT).
BIDMC, Harvard Medical School
- David C. Alsop, PhD, Pr. of Radiology
- Gopal Varma, PhD
  • Past Collaborators
    • 2016
      - Elise Van Obberghen, Neurologist fellow, (M2 training)
    • 2015
      - Yunfei Yang, M2 trainee/4th year of UTC Compiègne Engineer School (Compiègne)
      - Charles-Henri Andrieu, M1 trainee, International Master of photonics (POESII-Europhotonics), Aix-Marseille University
    • 2014
      - Guilherme Ribeiro, M2 trainee/4th year of Polytech Engineer School (Marseille)
  • ihMT project Grant Support
    • IRME, 2016
      Specific Spinal Cord Myelin imaging by inhomogeneous Magnetization Transfer (ihMT) MRI
    • Réseau PACASEP, 2015
      Optimisation théorique et expérimentale de l’imagerie du transfert d’aimantation inhomogène par IRM en vue d’applications cliniques
    • ARSEP, Fondation pour l’aider la recherche sur la sclérose en Plaques, 2015
      Development of a 3D inhomogeneous Magnetization Transfer (ihMT) technique, a new myelin specific MRI contrast, and first application to MS patients
    • Fondation A*MIDEX (Investissements d’avenir), AAP « Excellence Academy – PhD Collegium » 2014, ANR-11-IDEX-0001-02
      Inhomogeneous Magnetization Transfer Imaging at high magnetic field (11.75T) for specific myelin imaging
    • IRME, Institut pour la Recherche sur la Moelle Epinière, 2012
      Mesure de la perfusion Médullaire par IRM pour la caractérisation des patients atteints de Traumatismes

The ihMT project involves studies of underlying mechanisms and Physical characterization of this new contrast, validation of the technique as a myelin specific biomarker and Clinical applications.
The project mainly relies on MR Physics (modeling, numerical simulations), methodological developments (MR techniques, post-processing tools) transversally performed on specific phantoms/small animal using preclinical 7T&11.75T MR scanners, and on humans using clinical research 1.5T&3T MR scanners. This part of the project is developed in close collaboration with the division of MR research (Dir. D Alsop) of Beth Israel Deaconess Medical Center (Harvard Medical School, Boston, USA).
Clinical application of ihMT on MS patients is under investigation within protocols developed in collaboration with the department of Neurology (Dir. Jean Pelletier) of La Timone Hospital (Marseille).

  • Princeps Experiment: MT effects arise from exchange with one or more pools of magnetization with a wide, dipolar broadened line shape. A broad line is actually the instantaneous summation of many individual lines with different offset frequencies. Typically, spin components of these lines move rapidly from one frequency to another such that the different lines cannot be separated by RF excitation or saturation with RF powers available in vivo. Such rapidly exchanging lines are known as homogeneously broadened lines. The absence of the usual mechanisms, by which homogeneous broadening is achieved, suggest that inhomogeneous broadening may be present in large membranes, the main constituent of the myelin sheath.
    The ihMT technique is a method to detect the transfer of inhomogeneously broadened magnetization in the presence of a larger background of homogeneous MT. The resulting signal appears highly specific for myelinated structures (Fig. 1).

Fig. 1 Illustration of ihMT (d, e) specificity for myelinated structures. (a) anatomic and (b, c) regular MT. (From Varma et al, Magn Reson Med. 2015 Feb;73(2):614-22)

  • Experimental optimization at 1.5T: Optimization of the pulsed saturation scheme parameters, including the pulse width, the interpulse repetition time, the total saturation duration and the RF saturation power to increase the ihMT sensitivity and the contrast specificity allowed optimizing the ihMT contrast for practical clinical imaging experiments, and measuring the underlying contrast mechanisms and parameter dependencies that will contribute to a broader understanding of a quantitative ihMT model. (Fig. 2).

Fig. 2: (left) Typical optimized inhomogeneous ihMT images of CNS tissues and corresponding T2-weighted TSE acquisitions at 1.5T. (right) Pulse width and interpulse repetition time optimization. IhMT ratios in IC and cGM are shown as a function of the energy deposition ETR for different pulse widths and interpulse repetition times. (From Girard et al, Magn Reson Med. 2015 Jun;73(6):2111-21)
  • Physical Characterization: ihMT contrast can be explained physically as a dipolar order effect within bound molecules. In vivo data was qualitatively and quantitatively consistent with this physical theory. The inclusion of a dipolar reservoir in the existing two pool model for MT provided the means to model ihMT. By comparing the more effective saturation of dual frequency irradiation with the weaker saturation of single frequency irradiation, ihMT highlighted dipolar order effects in longer T1D tissues. Under this interpretation, contrast between myelinated tissues and other tissue types resulted from combined differences in T1D, the dipolar order relaxation time and f, the fraction of the bound pool with non-trivial T1Ds. This approach provided access to a new form of MRI contrast based on T1D differences between tissues.(Fig. 3).

Fig. 3: (left) Illustration of the model considered for bound pool magnetization and its internal dipolar interactions. Zeeman and dipolar reservoirs are derived from the same motion-restricted bound pool spins, but they change independently (a), and only interact in the presence of RF irradiation (b) according to Provotorov theory. (right) Plots of average data across IC ROI from single subject with dashed lines from fits to: (b) two bound pools Morrison model; and, (d) two bound pools CAA model. (From Varma et al, J Magn Reson. 2015 Nov;260:67-76)
  • ihMT vs MT-Asymmetry: The use of the double subtraction MT(+) + MT(-) - (MT(+/-) + MT(-/+)) to generate ihMT signal showed efficient correction for MT-asymmetry at 11.75T as long as⎪MTRasym⎪<4%. In this restricted range, MT-asymmetry signal did not contaminate ihMT quantification significantly. At 11.75T, it is suggested that the use of a center frequency in the range of -200 Hz<fc<-100 Hz (i.e. -0.4ppm< fc <-0.2ppm), that is the range of values that null MTRasym in Mu, would ensure close to optimal conditions are fulfilled over the whole brain. Beyond strong theoretical arguments, the distinct nature of MT-asymmetry and ihMT contrasts was further evidenced experimentally by measurement of non-zero ihMTR values for zero MT-asymmetry signal and subsequently emphasized by independent behaviors when varying the saturation parameters. IhMT varied non-linearly with saturation power, as opposed to the linear decrease of MTRasym over the explored range. Also the dependency of MTRasym and ihMTR on the interpulse delay (Δt) showed different behaviors, which highlighted fundamental differences in the rates of magnetization saturation transfer mechanism involved in each contrast. (Fig. 4).

Fig. 4: (left) Representative sets of single shot ihMT-RARE images (MT+, MT-, MTR, ihMTR, MTRasym) obtained on mouse at 11.75T, qualitatively illustrating the different nature of MT, ihMT and MT asymmetry contrasts. (right) MTR (a, d), MTRasym (b, e) and ihMTR (c, f) variations with fc values measured in IC. Saturation parameters were: PW/∆t=1/1.3ms, ETR=30 μT2.s and 60 μT2.s (a-c). PW/∆t=1/1.3ms, 3/3.3ms and 5/5.3ms, ETR=30 μT2.s (d-f). (From Prevost et al, Magn Reson Mater Phy 2016, DOI: 10.1007/s10334-015-0523-2)
  • Spinal Cord ihMT: Challenges for SC ihMT studies include a relatively coarse resolution compared to the small size of the cord, the presence of susceptibility effects from surrounding tissues, and most importantly sensitivity to the pulsatility of the cerebrospinal fluid (CSF), which induces motion in and around the cord. Indeed, in comparison with conventional MT, such motion may have more dramatic impact on ihMT because it has lower sensitivity (ihMT signal on the order of 10% of the unsaturated signal) and requires data subtraction from multiple images potentially acquired at different phases of motion. We presented a complete strategy for cervical SC ihMT imaging free of CSF pulsatility artifacts. The proposed method combines electro-cardiogram (ECG) synchronization and retrospective data pairing. This strategy aims at correcting for signal variations of long T1-components, such as CSF, that occur when a variable recovery delay is introduced in the sequence as a consequence of variable cardiac cycle. In comparison with other strategies correcting for such T1-recovery effects, the proposed method is model-free as it simply matches images acquired with a similar recovery period. A semi-automatic algorithm for data correction is presented along with accurate ihMT ratio quantification of the cord. Exquisite resulting image quality of the SC opens great possibility for further in vivo characterization of SC physiopathology using MRI. (Fig. 5).

Fig. 5: Effect of ECG synchronization on SC data. (a) Reference ECG triggered anatomical scan (T2w FSE) and corresponding MTR (b) and ihMTR (c) map obtained using optimized protocol (ECG synchronization and retrospective data pairing for ihMT). Examples of non-triggered acquisitions acquired on two different volunteers are displayed in (d) - (g). Whereas MTR data do not evidence strong signs of motion artifacts in the cord area (b) vs (d) and (e), the ihMTR data reconstructed from the same datasets show particularly strong CSF pulsatile artifacts ((f) and (g), green arrows), consistent with increased motion sensitivity of an image-subtraction based technique. ECG synchronization combined with the retrospective bias correction algorithm recovers exquisite SC image quality (c). (From Girard et al, Magn Reson Med. 2016, DOI 10.1002/mrm.26134)

Olivier Girard’s Publications


Journal Article

  • GIRARD O. M., CALLOT V., PREVOST V. H., ROBERT B., TASO M., RIBEIRO G., VARMA G., RANGWALA N., ALSOP D. C., DUHAMEL G. “Magnetization transfer from inhomogeneously broadened lines (ihMT): Improved imaging strategy for spinal cord applications.”. Magnetic Resonance in Medicine [En ligne]. 2017. Vol. 77, p. 581-591. Disponible sur : < >
    Résumé : Purpose Inhomogeneous magnetization transfer (ihMT) shows great promise for specific imaging of myelinated tissues. Whereas the ihMT technique has been previously applied in brain applications, the current report presents a strategy for cervical spinal cord (SC) imaging free of cerebrospinal fluid (CSF) pulsatility artifacts. Methods A pulsed ihMT preparation was combined with a single-shot HASTE readout. Electrocardiogram (ECG) synchronization was used to acquire all images during the quiescent phase of SC motion. However ihMT signal quantification errors may occur when a variable recovery delay is introduced in the sequence as a consequence of variable cardiac cycle. A semiautomatic retrospective correction algorithm, based on repetition time (TR) -matching, is proposed to correct for signal variations of long T1-components (e.g., CSF). Results The proposed strategy combining ECG synchronization and retrospective data pairing led to clean SC images free of CSF artifacts. Lower variability of the ihMT metrics were obtained with the correction algorithm, and allowed for shorter TR to be used, hence improving signal-to-noise ratio efficiency. Conclusion The proposed methodology enabled faster acquisitions, while offering robust ihMT quantification and exquisite SC image quality. This opens great perspectives for widening the in vivo characterization of SC physiopathology using MRI, such as studying white matter tracts microstructure or impairment in degenerative pathologies. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc.
    Mots-clés : crmbm, CSF pulsatility, ECG synchronization, ihMT, Inhomogeneous magnetization transfer, motion correction, myelin, Spinal Cord, white matter.

  • PREVOST V. H., GIRARD O. M., MCHINDA S., VARMA G., ALSOP D. C., DUHAMEL G. “Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time (T1D) filtering.”. NMR in Biomedicine [En ligne]. 2017. Disponible sur : < >
    Résumé : A pulsed inhomogeneous magnetization transfer (ihMT)‐prepared fast imaging sequence was implemented at 11.75 T for preclinical studies on mouse central nervous system. A strategy based on filtering the...
    Mots-clés : crmbm.


Journal Article

  • PREVOST V. H., GIRARD O. M., VARMA G., ALSOP D. C., DUHAMEL G. “Minimizing the effects of magnetization transfer asymmetry on inhomogeneous magnetization transfer (ihMT) at ultra-high magnetic field (11.75 T).”. Magma (New York, N.Y.) [En ligne]. 2016. Vol. 29, n°4, p. 699-709. Disponible sur : < > (consulté le no date)
    Résumé : OBJECTIVES: The recently reported inhomogeneous magnetization transfer technique (ihMT) has been proposed for specific imaging of inhomogeneously broadened lines, and has shown great promise for characterizing myelinated tissues. The ihMT contrast is obtained by subtracting magnetization transfer images obtained with simultaneous saturation at positive and negative frequency offsets (dual frequency saturation experiment, MT (+/-)) from those obtained with single frequency saturation (MT (+)) at the same total power. Hence, ihMT may be biased by MT-asymmetry, especially at ultra-high magnetic field. Use of the average of single positive and negative frequency offset saturation MT images, i.e., (MT (+)+MT (-)) has been proposed to correct the ihMT signal from MT-asymmetry signal. MATERIALS AND METHODS: The efficiency of this correction method was experimentally assessed in this study, performed at 11.75 T on mice. Quantitative corrected ihMT and MT-asymmetry ratios (ihMTR and MTRasym) were measured in mouse brain structures for several MT-asymmetry magnitudes and different saturation parameter sets. RESULTS: Our results indicated a "safe" range of magnitudes (/MTRasym/<4 %) for which MT-asymmetry signal did not bias the corrected ihMT signal. Moreover, experimental evidence of the different natures of both MT-asymmetry and inhomogeneous MT contrasts were provided. In particular, non-zero ihMT ratios were obtained at zero MTRasym values. CONCLUSION: MTRasym is not a confounding factor for ihMT quantification, even at ultra-high field, as long as MTRasym is restricted to ±4 %.
    Mots-clés : Biomedical Engineering, Computer Appl. in Life Sciences, crmbm, Dipolar order, Dipolar relaxation time, Health Informatics, ihMT, Imaging / Radiology, Inhomogeneous magnetization transfer, MT-asymmetry, myelin, Solid State Physics.

  • TASO M., GIRARD O. M., DUHAMEL G., LE TROTER A., FEIWEIER T., GUYE M., RANJEVA J. - P., CALLOT V. “Tract-specific and age-related variations of the spinal cord microstructure: a multi-parametric MRI study using diffusion tensor imaging (DTI) and inhomogeneous magnetization transfer (ihMT).”. NMR in biomedicine [En ligne]. 2016. Vol. 29, n°6, p. 817-832. Disponible sur : < > (consulté le no date)
    Résumé : Being able to finely characterize the spinal cord (SC) microstructure and its alterations is a key point when investigating neural damage mechanisms encountered in different central nervous system (CNS) pathologies, such as multiple sclerosis, amyotrophic lateral sclerosis or myelopathy. Based on novel methods, including inhomogeneous magnetization transfer (ihMT) and dedicated SC probabilistic atlas post-processing, the present study focuses on the in vivo characterization of the healthy SC tissue in terms of regional microstructure differences between (i) upper and lower cervical vertebral levels and (ii) sensory and motor tracts, as well as differences attributed to normal aging. Forty-eight healthy volunteers aged from 20 to 70 years old were included in the study and scanned at 3 T using axial high-resolution T2 *-w imaging, diffusion tensor imaging (DTI) and ihMT, at two vertebral levels (C2 and C5). A processing pipeline with minimal user intervention, SC segmentation and spatial normalization into a reference space was implemented in order to assess quantitative morphological and structural parameters (cross-sectional areas, scalar DTI and MT/ihMT metrics) in specific white and gray matter regions of interest. The multi-parametric MRI metrics collected allowed upper and lower cervical levels to be distinguished, with higher ihMT ratio (ihMTR), higher axial diffusivity (λ∥ ) and lower radial diffusivity (λ⊥ ) at C2 compared with C5. Significant differences were also observed between white matter fascicles, with higher ihMTR and lower λ∥ in motor tracts compared with posterior sensory tracts. Finally, aging was found to be associated with significant metric alterations (decreased ihMTR and λ∥ ). The methodology proposed here, which can be easily transferred to the clinic, provides new insights for SC characterization. It bears great potential to study focal and diffuse SC damage in neurodegenerative and demyelinating diseases. Copyright © 2016 John Wiley & Sons, Ltd.
    Mots-clés : Aging, crmbm, diffusion tensor imaging (DTI), ihMT, inhomogeneous magnetization transfer (ihMT), microstructure, multi-parametric MRI, Spinal Cord.

  • VARMA G., GIRARD O. M., PREVOST V. H., GRANT A. K., DUHAMEL G., ALSOP D. C. “In vivo measurement of a new source of contrast, the dipolar relaxation time, T1D , using a modified inhomogeneous magnetization transfer (ihMT) sequence.”. Magnetic Resonance in Medicine [En ligne]. 2016. Disponible sur : < > (consulté le no date)
    Résumé : PURPOSE: This paper describes a technique that can be used in vivo to measure the dipolar relaxation time, T1D , of macromolecular protons contributing to magnetization transfer (MT) in tissues and to produce quantitative T1D maps. THEORY AND METHODS: The technique builds upon the inhomogeneous MT (ihMT) technique that is particularly sensitive to tissue components with long T1D . A standard ihMT experiment was altered to introduce a variable time for switching between positive and negative offset frequencies for RF saturation. A model for the dependence of ihMT was developed and used to fit data acquired in vivo. RESULTS: Application of the method to images from brains of healthy volunteers produced values of T1D  = (5.9 ± 1.2) ms in gray matter and T1D  = (6.2 ± 0.4) ms in white matter regions and provided maps of the T1D parameter. CONCLUSION: The model and experiments described provide access to a new relaxation characteristic of tissue with potentially unique diagnostic information. Magn Reson Med, 2016. © 2016 International Society for Magnetic Resonance in Medicine.
    Mots-clés : crmbm, Dipolar relaxation, ihMT, Inhomogeneous magnetization transfer, MT, myelin, Quantitative magnetization transfer.


Journal Article

  • GIRARD O. M., PREVOST V. H., VARMA G., COZZONE P. J., ALSOP D. C., DUHAMEL G. “Magnetization transfer from inhomogeneously broadened lines (ihMT): Experimental optimization of saturation parameters for human brain imaging at 1.5 Tesla.”. Magnetic Resonance in Medicine [En ligne]. 2015. Vol. 73, n°6, p. 2111-2121. Disponible sur : < > (consulté le no date)
    Résumé : PURPOSE: Recently a new MR endogenous contrast mechanism was reported. It allows specifically imaging the magnetization transfer (MT) effect arising from inhomogeneously broadened components of the NMR spectrum, and was hence dubbed ihMT. Such unique NMR lineshape properties are presumably occurring in myelin because of its specifically ordered, multilayered sheath structure. Here, optimization of a pulsed ihMT preparation module is presented to provide guidance for future studies and improve the understanding of underlying contrast mechanisms. METHODS: This study was performed at 1.5 Tesla on healthy volunteers. A pulsed ihMT preparation was implemented in combination with a HASTE readout module. The pulse width, interpulse repetition time, total saturation duration and RF saturation power were considered for optimization of the ihMT sensitivity and contrast. RESULTS: An optimal configuration of the preparation module was derived, leading to 10% ihMT signal in internal capsule (relative to unsaturated data) and around 200% signal increase relative to gray matter, i.e., approximately 10-fold superior contrast compared with conventional MT ratios, measured under similar experimental conditions. CONCLUSION: Overall the ihMT sequence was robust, sensitive and very specific for white matter. These findings suggest great potential for assessing brain myelination and for better characterization of myelin related disorders. Magn Reson Med 73:2111-2121, 2015. © 2014 Wiley Periodicals, Inc.
    Mots-clés : crmbm, ihMT, inhomogeneously broadened lines, Magnetization transfer, myelin, specificity, white matter.

  • LAISTLER E., POIRIER-QUINOT M., LAMBERT S. A., DUBUISSON R. - M., GIRARD O. M., MOSER E., DARRASSE L., GINEFRI J. - C. “In vivo MR imaging of the human skin at subnanoliter resolution using a superconducting surface coil at 1.5 Tesla.”. Journal of magnetic resonance imaging: JMRI [En ligne]. 2015. Vol. 41, n°2, p. 496-504. Disponible sur : < > (consulté le no date)
    Résumé : PURPOSE: To demonstrate the feasibility of a highly sensitive superconducting surface coil for microscopic MRI of the human skin in vivo in a clinical 1.5 Tesla (T) scanner. MATERIALS AND METHODS: A 12.4-mm high-temperature superconducting coil was used at 1.5T for phantom and in vivo skin imaging. Images were inspected to identify fine anatomical skin structures. Signal-to-noise ratio (SNR) improvement by the high-temperature superconducting (HTS) coil, as compared to a commercial MR microscopy coil was quantified from phantom imaging; the gain over a geometrically identical coil made from copper (cooled or not) was theoretically deduced. Noise sources were identified to evaluate the potential of HTS coils for future studies. RESULTS: In vivo skin images with isotropic 80 μm resolution were demonstrated revealing fine anatomical structures. The HTS coil improved SNR by a factor 32 over the reference coil in a nonloading phantom. For calf imaging, SNR gains of 380% and 30% can be expected over an identical copper coil at room temperature and 77 K, respectively. CONCLUSION: The high sensitivity of HTS coils allows for microscopic imaging of the skin at 1.5T and could serve as a tool for dermatology in a clinical setting.

  • PREVOST V. H., GIRARD O. M., CALLOT V., COZZONE P. J., DUHAMEL G. “Fast imaging strategies for mouse kidney perfusion measurement with pseudocontinuous arterial spin labeling (pCASL) at ultra high magnetic field (11.75 tesla).”. Journal of Magnetic Resonance Imaging [En ligne]. 2015. Vol. 42, n°4, p. 999-1008. Disponible sur : < >
    Résumé : Background To derive an adapted protocol at ultra high magnetic field for mouse kidney perfusion measurements using pCASL in combination with three widely available fast imaging readouts: segmented SE EPI (sSE EPI), RARE, and TrueFISP. Methods pCASL sSE EPI, pCASL RARE, and pCASL TrueFISP were used for the acquisition of mouse kidney perfusion images in the axial and coronal planes at 11.75T. Results were compared in terms of perfusion sensitivity, signal-to-noise ratio (SNR), blood flow values, intrasession and intersession repeatability, and image quality (subjectively classified into three grades: good, satisfactory, and unacceptable). Results Renal cortex perfusion measurements were performed within 2 min with pCASL RARE/pCASL TrueFISP and 4 min with pCASL sSE EPI. In an axial direction, SNR values of 6.6/5.6/2.8, perfusion sensitivity values of 16.1 ± 3.7/13.6 ± 2.4/13.4 ± 1.0 %, blood flow values of 679 ± 149/466 ± 111/572 ± 46 mL/100 g/min and in-ROI variations values of 192/161/181 mL/100 g/min were obtained with pCASL sSE EPI/pCASL RARE/pCASL TrueFISP. Highest SNR per unit of time (1.8) and highest intra/intersession reliability (92.9% and 95.1%) were obtained with pCASL RARE, which additionally presented highly reproducible satisfactory image quality. In coronal plane, significantly lower SNR, perfusion sensitivity and perfusion values were obtained for all techniques compared with that in the axial plane (P < 0.05) due to magnetization saturation effects. Conclusion pCASL RARE demonstrated more advantages for longitudinal preclinical kidney perfusion studies at ultra high magnetic field. J. Magn. Reson. Imaging 2015;42:999–1008.
    Mots-clés : crmbm, high magnetic field, mouse kidney, perfusion, pseudocontinuous ASL, RBF.

  • VARMA G., GIRARD O. M., PREVOST V. H., GRANT A. K., DUHAMEL G., ALSOP D. C. “Interpretation of magnetization transfer from inhomogeneously broadened lines (ihMT) in tissues as a dipolar order effect within motion restricted molecules.”. Journal of Magnetic Resonance (San Diego, Calif.: 1997) [En ligne]. 2015. Vol. 260, p. 67-76. Disponible sur : < > (consulté le no date)
    Résumé : Comparison of off-resonance saturation with single and dual frequency irradiation indicates a contribution of inhomogeneously broadened lines to magnetization transfer in tissues. This inhomogeneous magnetization transfer (ihMT) phenomenon can be exploited to produce images that highlight tissues containing myelin, in vivo. Here, a model for ihMT is described that includes dipolar order effects from magnetization associated with motion-restricted macromolecules. In this model, equal irradiation at positive and negative frequency offsets eliminates dipolar order and achieves greater saturation than irradiation at a single offset frequency using the same power. Fitting of mouse and human volunteer brain data at different irradiation powers and offset frequencies was performed to assess the relevance of the model and approximate tissue parameters. A key parameter in determining ihMT signal was found to be the relaxation time T1D associated with the dipolar order reservoir and the fraction f of the semi-solid, bound magnetization that possessed a nonzero T1D. Indeed, better fits of myelinated tissue were achieved when assuming f≠1. From such fits, estimated T1Ds of mice in the white matter, (34±14)ms, were much longer than in muscle, T1D=(1±1)ms and the average f from white matter volunteer data was 2.2 times greater than that in grey matter. The combination of f and longer T1Ds was primarily responsible for the much higher ihMT in myelinated tissues, and provided explanation for the species variation. This dipolar order ihMT model should help guide future research, pulse sequence optimization, and clinical applications.
    Mots-clés : crmbm, Dipolar relaxation, ihMT, Inhomogeneous magnetization transfer, MT, myelin, Provotorov theory, Quantitative magnetization transfer, Saturation, Spin temperature, SuperLorentzian lineshape.


Journal Article

  • DUHAMEL G., PREVOST V., GIRARD O. M., CALLOT V., COZZONE P. J. “High-resolution mouse kidney perfusion imaging by pseudo-continuous arterial spin labeling at 11.75T.”. Magnetic Resonance in Medicine [En ligne]. 2014. Vol. 71, n°3, p. 1186-1196. Disponible sur : < >
    Résumé : Purpose Quantitative measure of blood flow provides important information regarding renal function, nephropathies and viability of kidney transplantation. Therefore, a method that would allow quantitative and reliable assessment of the renal microvascular perfusion would be very valuable. Arterial spin labeling Magnetic Resonance Imaging has started to be widely used for human studies. For rodents though, despite the increasing number of transgenic mouse models, renal perfusion Magnetic Resonance Imaging has been only sparsely reported. This study investigated the use of FAIR (flow-sensitive alternating inversion recovery) and pseudo-continuous arterial spin labeling (pCASL) for mouse renal blood flow measurements. Methods FAIR and pCASL were compared in terms of sensitivity, absolute quantification, reproducibility and flexibility of implementation. Multislice and coronal imaging were also investigated. Studies were performed at 11.75 T with volumic transmitter/receiver radiofrequency coils and fast imaging. Results pCASL demonstrated better experimental flexibility and higher sensitivity compared to FAIR (> +20%). Renal blood flow values in the range of 550–750 mL/100 g/min for the cortex and of 140–230 mL/100 g/min for the medulla, consistent with literature data, were measured. Conclusion pCASL was successfully applied at very high field for mouse renal blood flow measurements, demonstrating high sensitivity, flexibility and multislice imaging capability. pCASL may be considered as a method of choice for mouse kidney perfusion studies. Magn Reson Med 71:1186–1196, 2014. © 2013 Wiley Periodicals, Inc.
    Mots-clés : crmbm, high magnetic field, mouse kidney, perfusion, pseudo-continuous ASL, RBF.


Book Section
Journal Article

  • LIAU J., SHIEHMORTEZA M., GIRARD O. M., SIRLIN C. B., BYDDER M. “Evaluation of MRI fat fraction in the liver and spine pre and post SPIO infusion.”. Magnetic Resonance Imaging [En ligne]. 2013. Vol. 31, n°6, p. 1012-1016. Disponible sur : < >
    Résumé : Abstract This study evaluates the robustness of a magnetic resonance (MR) fat quantification method to changes in R2* caused by an intravenous infusion of superparamagnetic iron oxide (SPIO) contrast agent. The R2* and proton density fat fraction (PDFF) were measured in liver and spine in 14 subjects using an investigational sequence (IDEAL IQ) provided by the MR scanner vendor. Measurements were made before and after SPIO infusion. Results showed SPIO significantly increased R2* in both liver (p = 8.8 × 10− 8) and spine (p =1.3 × 10− 2) but PDFFs were not significantly different in either the liver (p = 5.5 × 10− 1) or the spine (p = 5.6 × 10− 1). These results confirm that the IDEAL IQ method of fat quantification is robust to changes in R2*.
    Mots-clés : Fat fractionSPIO, Liver, MRI, Spine, SPIO.


Journal Article

  • GIRARD O. M., RAMIREZ R., MCCARTY S., MATTREY R. F. “Toward absolute quantification of iron oxide nanoparticles as well as cell internalized fraction using multiparametric MRI.”. Contrast Media & Molecular Imaging [En ligne]. 2012. Vol. 7, n°4, p. 411–417. Disponible sur : < >
    Résumé : Iron oxide nanoparticles (IONPs) are widely used as MR contrast agents because of their strong magnetic properties and broad range of applications. The contrast induced by IONPs typically depends on concentration, water accessibility, particle size and heterogeneity of IONP distribution within the microenvironment. Although the latter could be a tool to assess local physiological effects at the molecular level, it renders IONP quantification from relaxation measurements challenging. This study aims to quantify IONP concentration using susceptibility measurements. In addition, further analysis of relaxation data is proposed to extract quantitative information about the IONP spatial distribution. Mesenchymal stem cells were labeled with IONPs and the IONP concentration measured by mass spectroscopy. MR relaxation parameters (T1, T2, T2*) as well as magnetic susceptibility of cylindrical samples containing serial dilutions of mixtures of free and cell-internalized IONPs were measured and correlated with IONP concentration. Unlike relaxation data, magnetic susceptibility was independent of whether IONPs were free or internalized, making it an excellent candidate for IONP quantification. Using IONP concentration derived from mass spectroscopy and measured relaxation times, free and internalized IONP fractions were accurately calculated. Magnetic susceptibility was shown to be a robust technique to measure IONP concentration in this preliminary study. Novel imaging-based susceptibility mapping techniques could prove to be valuable tools to quantify IONP concentration directly by MRI, for samples of arbitrary shape. Combined with relaxation time mapping techniques, especially T2 and T2*, this could be an efficient way to measure both IONP concentration and the internalized IONP fraction in vivo using MRI, to gain insight into tissue function and molecular imaging paradigms. Copyright © 2012 John Wiley & Sons, Ltd.
    Mots-clés : cellular imaging, iron oxide nanoparticle, magnetic susceptibility, quantification, relaxation, responsive agent.


Journal Article

  • AGEMY L., FRIEDMANN-MORVINSKI D., KOTAMRAJU V. R., ROTH L., SUGAHARA K. N., GIRARD O. M., MATTREY R. F., VERMA I. M., RUOSLAHTI E. “Targeted nanoparticle enhanced proapoptotic peptide as potential therapy for glioblastoma.”. Proceedings of the National Academy of Sciences [En ligne]. 2011. Vol. 108, n°42, p. 17450-17455. Disponible sur : < >
    Résumé : Antiangiogenic therapy can produce transient tumor regression in glioblastoma (GBM), but no prolongation in patient survival has been achieved. We have constructed a nanosystem targeted to tumor vasculature that incorporates three elements: (i) a tumor-homing peptide that specifically delivers its payload to the mitochondria of tumor endothelial cells and tumor cells, (ii) conjugation of this homing peptide with a proapoptotic peptide that acts on mitochondria, and (iii) multivalent presentation on iron oxide nanoparticles, which enhances the proapoptotic activity. The iron oxide component of the nanoparticles enabled imaging of GBM tumors in mice. Systemic treatment of GBM-bearing mice with the nanoparticles eradicated most tumors in one GBM mouse model and significantly delayed tumor development in another. Coinjecting the nanoparticles with a tumor-penetrating peptide further enhanced the therapeutic effect. Both models used have proven completely resistant to other therapies, suggesting clinical potential of our nanosystem.
    Mots-clés : angiogenesis, Apoptosis, tumor targeting, tumor treatment.

  • BYDDER M., GIRARD O., HAMILTON G. “Mapping the double bonds in triglycerides.”. Magnetic Resonance Imaging [En ligne]. 2011. Vol. 29, n°8, p. 1041-1046. Disponible sur : < >
    Résumé : This study presents and validates a theoretical model for estimating the number of double bonds in triglyceride molecules using magnetic resonance imaging. The model enables reliable estimation of the number of double bonds from a small number of time points, as are typically acquired with chemical shift imaging. Prior knowledge from the US Department of Agriculture (USDA) is used to constrain the properties of triglyceride. Validation in oil phantoms shows agreement between the measured number of double bonds and USDA reference values (correlation 0.95, significance P=.0003, slope 0.95±0.31, intercept 0.08±1.24). Feasibility in a human subject was demonstrated using a long breath-hold (43 s) scan.
    Mots-clés : Chemical shift, Dixon, Phase, Water–fat separation.

  • CARL M., SANAL H. T., DIAZ E., DU J., GIRARD O., STATUM S., ZNAMIROWSKI R., CHUNG C. B. “Optimizing MR signal contrast of the temporomandibular joint disk.”. Journal of Magnetic Resonance Imaging [En ligne]. 2011. Vol. 34, n°6, p. 1458–1464. Disponible sur : < >
    Résumé : Purpose:To use a tissue specific algorithm to numerically optimize UTE sequence parameters to maximize contrast within temporomandibular joint (TMJ) donor tissue.Materials and Methods:A TMJ specimen tissue block was sectioned in a true sagittal plane and imaged at 3 Tesla (T) using UTE pulse sequences with dual echo subtraction. The MR tissue properties (PD, T2, T2*, and T1) were measured and subsequently used to calculate the optimum sequences parameters (repetition time [TR], echo time [TE], and θ).Results:It was found that the main contrast available in the TMJ could be obtained from T2 (or T2*) contrast. With the first echo time fixed at 8 μs and using TR = 200 ms, the optimum parameters were found to be: θ ≈ 60°, and TE2 ≈ 15 ms, when the second echo is acquired using a gradient echo and θ ≈ 120°, and TE2 ≈ 15 ms, when the second echo is acquired using a spin echo.Conclusion:Our results show that MR signal contrast can be optimized between tissues in a systematic manner. The MR contrast within the TMJ was successfully optimized with facile delineation between disc and soft tissues. J. Magn. Reson. Imaging 2011;. © 2011 Wiley Periodicals, Inc.
    Mots-clés : contrast optimization, TMJ, UTE.

  • GIRARD O. M., DU J., AGEMY L., SUGAHARA K. N., KOTAMRAJU V. R., RUOSLAHTI E., BYDDER G. M., MATTREY R. F. “Optimization of iron oxide nanoparticle detection using ultrashort echo time pulse sequences: Comparison of T1, T2*, and synergistic T1 − T2* contrast mechanisms.”. Magnetic Resonance in Medicine [En ligne]. 2011. Vol. 65, n°6, p. 1649–1660. Disponible sur : < >
    Résumé : Iron oxide nanoparticles (IONPs) are used in various MRI applications as negative contrast agents. A major challenge is to distinguish regions of signal void due to IONPs from those due to low signal tissues or susceptibility artifacts. To overcome this limitation, several positive contrast strategies have been proposed. Relying on IONP T1 shortening effects to generate positive contrast is a particularly appealing strategy because it should provide additional specificity when associated with the usual negative contrast from effective transverse relaxation time (T2*) effects. In this article, ultrashort echo time imaging is shown to be a powerful technique which can take full advantage of both contrast mechanisms. Methods of comparing T1 and T2* contrast efficiency are described and general rules that allow optimizing IONP detection sensitivity are derived. Contrary to conventional wisdom, optimizing T1 contrast is often a good strategy for imaging IONPs. Under certain conditions, subtraction of a later echo signal from the ultrashort echo time signal not only improves IONP specificity by providing long T2* background suppression but also increases detection sensitivity, as it enables a synergistic combination of usually antagonist T1 and T2* contrasts. In vitro experiments support our theory, and a molecular imaging application is demonstrated using tumor-targeted IONPs in vivo. Magn Reson Med, 2011. © 2011 Wiley-Liss, Inc.
    Mots-clés : iron oxide nanoparticle, positive contrast, sequence optimization, UTE.


Journal Article

  • AGEMY L., SUGAHARA K. N., KOTAMRAJU V. R., GUJRATY K., GIRARD O. M., KONO Y., MATTREY R. F., PARK J. - H., SAILOR M. J., JIMENEZ A. I., CATIVIELA C., ZANUY D., SAYAGO F. J., ALEMAN C., NUSSINOV R., RUOSLAHTI E. “Nanoparticle-induced vascular blockade in human prostate cancer.”. Blood [En ligne]. 2010. Vol. 116, n°15, p. 2847-2856. Disponible sur : < >
    Résumé : The tumor-homing pentapeptide CREKA (Cys-Arg-Glu-Lys-Ala) specifically homes to tumors by binding to fibrin and fibrin-associated clotted plasma proteins in tumor vessels. Previous results show that CREKA-coated superparamagnetic iron oxide particles can cause additional clotting in tumor vessels, which creates more binding sites for the peptide. We have used this self-amplifying homing system to develop theranostic nanoparticles that simultaneously serve as an imaging agent and inhibit tumor growth by obstructing tumor circulation through blood clotting. The CREKA nanoparticles were combined with nanoparticles coated with another tumor-homing peptide, CRKDKC, and nanoparticles with an elongated shape (nanoworms) were used for improved binding efficacy. The efficacy of the CREKA peptide was then increased by replacing some residues with nonproteinogenic counterparts, which increased the stability of the peptide in the circulation. Treatment of mice bearing orthotopic human prostate cancer tumors with the targeted nanoworms caused extensive clotting in tumor vessels, whereas no clotting was observed in the vessels of normal tissues. Optical and magnetic resonance imaging confirmed tumor-specific targeting of the nanoworms, and ultrasound imaging showed reduced blood flow in tumor vessels. Treatment of mice with prostate cancer with multiple doses of the nanoworms induced tumor necrosis and a highly significant reduction in tumor growth.

  • BYDDER M., SHIEHMORTEZA M., YOKOO T., SUGAY S., MIDDLETON M. S., GIRARD O., SCHROEDER M. E., WOLFSON T., GAMST A., SIRLIN C. “Assessment of liver fat quantification in the presence of iron.”. Magnetic Resonance Imaging [En ligne]. 2010. Vol. 28, n°6, p. 767-776. Disponible sur : < >
    Résumé : This study assesses the stability of magnetic resonance liver fat measurements against changes in T2* due to the presence of iron, which is a confound for accurate quantification. The liver T2* was experimentally shortened by intravenous infusion of a super paramagnetic iron oxide contrast agent. Low flip angle multiecho gradient echo sequences were performed before, during and after infusion. The liver fat fraction (FF) was calculated in co-localized regions-of-interest using T2* models that assumed no decay, monoexponential decay and biexponential decay. Results show that, when T2* was neglected, there was a strong underestimation of FF and with monoexponential decay there was a weak overestimation of FF. Curve-fitting using the biexponential decay was found to be problematic. The overestimation of FF may be due to remaining deficiencies in the model, although is unlikely to be important for clinical diagnosis of steatosis.
    Mots-clés : Fat quantification, Iron, Liver, SPIO.


Journal Article

  • SUGAHARA K. N., TEESALU T., KARMALI P. P., KOTAMRAJU V. R., AGEMY L., GIRARD O. M., HANAHAN D., MATTREY R. F., RUOSLAHTI E. “Tissue-Penetrating Delivery of Compounds and Nanoparticles into Tumors.”. Cancer Cell [En ligne]. 2009. Vol. 16, n°6, p. 510-520. Disponible sur : < >
    Résumé : Summary Poor penetration of drugs into tumors is a major obstacle in tumor treatment. We describe a strategy for peptide-mediated delivery of compounds deep into the tumor parenchyma that uses a tumor-homing peptide, iRGD (CRGDK/RGPD/EC). Intravenously injected compounds coupled to iRGD bound to tumor vessels and spread into the extravascular tumor parenchyma, whereas conventional RGD peptides only delivered the cargo to the blood vessels. iRGD homes to tumors through a three-step process: the RGD motif mediates binding to αv integrins on tumor endothelium and a proteolytic cleavage then exposes a binding motif for neuropilin-1, which mediates penetration into tissue and cells. Conjugation to iRGD significantly improved the sensitivity of tumor-imaging agents and enhanced the activity of an antitumor drug.
    Mots-clés : CELLCYCLE.


Journal Article

  • POIRIER-QUINOT M., GINEFRI J. - C., GIRARD O., ROBERT P., DARRASSE L. “Performance of a miniature high-temperature superconducting (HTS) surface coil for in vivo microimaging of the mouse in a standard 1.5T clinical whole-body scanner.”. Magnetic Resonance in Medicine [En ligne]. 2008. Vol. 60, n°4, p. 917–927. Disponible sur : < >
    Résumé : The performance of a 12-mm high-temperature superconducting (HTS) surface coil for in vivo microimaging of mice in a standard 1.5T clinical whole-body scanner was investigated. Systematic evaluation of MR image quality was conducted on saline phantoms with various conductivities to derive the sensitivity improvement brought by the HTS coil compared with a similar room-temperature copper coil. The observed signal-to-noise ratio (SNR) was correlated to the loaded quality factor of the radio frequency (RF) coils and is theoretically validated with respect to the noise contribution of the MR acquisition channel. The expected in vivo SNR gain was then extrapolated for different anatomical sites by monitoring the quality factor in situ during animal imaging experiments. Typical SNR gains of 9.8, 9.8, 5.4, and 11.6 were found for brain, knee, back, and subcutaneous implanted tumors, respectively, over a series of mice. Excellent in vivo image quality was demonstrated in 16 min with native voxels down to (59 μm)3 with an SNR of 20. The HTS coil technology opens the way, for the first time at the current field strength of clinical MR scanners, to spatial resolutions below 10–3 mm3 in living mice, which until now were only accessible to specialized high-field MR microscopes. Magn Reson Med 60:917–927, 2008. © 2008 Wiley-Liss, Inc.
    Mots-clés : clinical whole-body scanner, high-temperature superconductor (HTS), miniature radiofrequency (RF) coil, Mouse, MR microscopy, small animal.


Journal Article

  • GINEFRI J. - C., POIRIER-QUINOT M., GIRARD O., DARRASSE L. “Technical aspects: Development, manufacture and installation of a cryo-cooled HTS coil system for high-resolution in-vivo imaging of the mouse at 1.5 T.”. Methods [En ligne]. 2007. Vol. 43, n°1, p. 54-67. Disponible sur : < >
    Résumé : Signal-to-noise ratio improvement is of major importance to achieve microscopic spatial resolution in magnetic resonance experiments. Magnetic resonance imaging of small animals is particularly concerned since it typically requires voxels of less than (100 μm)3 to observe the small anatomical structures having size reduction by a factor of more than 10 as compared to human being. The signal-to-noise ratio can be increased by working at high static magnetic field strengths, but the biomedical interest of such high-field systems may be limited due to field-dependant contrast mechanisms and severe technological difficulties. An alternative approach that allows working in clinical imaging system is to improve the sensitivity of the radio-frequency receiver coil. This can be done using small cryogenically operated coils made either of copper or high-temperature superconducting material. We report the technological development of cryo-cooled superconducting coils for high-resolution imaging in a whole-body magnetic resonance scanner operating at 1.5 T. The technological background supporting this development is first addressed, including HTS coil design, simulation tools, cryogenic mean description and electrical characterization procedure. To illustrate the performances of superconducting coils for magnetic resonance imaging at intermediate field strength, in-vivo mouse images of various anatomic sites acquired with a 12 mm diameter cryo-cooled superconducting coil are presented.
    Mots-clés : Coil, In-vivo, Micro-imaging, Mouse, Superconducting, Whole-body.

  • GIRARD O., GINEFRI J. - C., POIRIER-QUINOT M., DARRASSE L. “Method for nonlinear characterization of radio frequency coils made of high temperature superconducting material in view of magnetic resonance imaging applications.”. The Review of scientific instruments [En ligne]. 2007. Vol. 78, n°12, p. 124703. Disponible sur : < > (consulté le no date)
    Résumé : A contactless method based on reflectometry to accurately characterize an inductive radio frequency (rf) resonator even in the occurrence of a strong electrical nonlinearity is presented. Nonlinear extraction of the unloaded quality factor and resonance frequency is possible by combining an initial low-level swept-frequency calibration with high-level single-frequency measurements. The extraction protocol relies on a simple intrinsic R, L, C model and does not involve a fitting procedure according to a particular nonlinearity model. It includes a correction for strong coupling conditions between the probe and the rf coil, which allows extending the analysis over a wide range of transmitted power. Electrical modeling based on the extracted intrinsic data allows predicting the coil behavior when loaded by any kind of matching network. The method will have implications in different domains such as Magnetic Resonance (MR) applications with superconducting probe heads or analysis of rf properties in nonlinear materials. The method is demonstrated here by characterizing a high temperature superconducting (HTS) coil dedicated to MR imaging at 64 MHz. The coil consists in a multiturn spiral design that is self-resonant close to the MR frequency of interest. The Q factor and the resonance frequency are determined as a function of the actual power dissipated in the HTS coil accounting for losses occurring in the measurement system. Further characteristics of the HTS coil are considered in the present paper. The relation between the transmitted power and the magnetic field generated by the coil, which is the most relevant characteristics for MR applications, is directly accessible. The equivalent impedance of the coil under test is also expressed as a function of the total current flowing in the windings. The method could be extended to assess the fundamental properties of the nonlinear material (e.g., the London penetration depth or the critical current density) by including any pertinent model.
    Mots-clés : Computer Simulation, Computer-Aided Design, Electric Conductivity, Equipment Design, Equipment Failure Analysis, Magnetic Resonance Imaging, Magnetics, Models, Theoretical, Nonlinear Dynamics, Reproducibility of Results, Sensitivity and Specificity, Transducers.

  • WOYTASIK M., GINEFRI J. - C., RAYNAUD J. - S., POIRIER-QUINOT M., DUFOUR-GERGAM E., GRANDCHAMP J. - P., GIRARD O., ROBERT P., GILLES J. - P., MARTINCIC E., DARRASSE L. “Characterization of flexible RF microcoils dedicated to local MRI.”. Microsystem Technologies-Micro-and Nanosystems-Information Storage and Processing Systems [En ligne]. 2007. Vol. 13, n°11-12, p. 1575-1580. Disponible sur : < > (consulté le no date)
    Résumé : In magnetic resonance imaging (MRI), the electrical performance of the
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