Inhomogeneous Magnetization Transfer (ihMT)

Research Works

Principal investigators : Guillaume Duhamel, PhD        Olivier Girard, PhD

Members

Lucas Soustelle, PhD      Evgenios Kornaropoulos, PhD

Timothy Anderson, PhD Student

Alumni

Andreea Hertanu (PhD student, 2018-2022)
Victor Carvalho (PhD student, 2016-2020)
Samira Mchinda (PhD student, 2015-2019)
Valentin Prévost (PhD student, 2014-2018)

Research

Inhomogeneous magnetization transfer technique (ihMT) is an emerging MT-based technique, whose mechanisms can generate strong contrast between different tissues by exploiting a previously unexplored degree of freedom of the NMR spectrum of broad macromolecular lines, namely the dipolar order. Dipolar order is intrinsically linked to macromolecules composition, dynamics and architecture, and is characterized by the dipolar order relaxation time, T1D. T1D-relaxation is driven by molecular motions with a specific sensitivity to slow motional processes such as lipid membrane collective motions, which are not accessible with standard MRI contrast such as T1 and T2 relaxometry and hence, ihMT opens a new way to visualize, characterize and distinguish properties of soft tissues based on their T1D values. The concepts of ihMT are described in a recent review (Alsop et al, NMR biomed 2022).

We develop a translational research program (animal <-> human, and fundamental <-> applications) around the ihMT technique, which aims at i) the exploration of the physical mechanisms underlying T1D relaxation and ihMT, ii) the validation of the sensitivity and specificity of ihMT for myelin, iii) the transfer of this technology to different clinical magnetic fields for improved sensitivity, and iv) its application to demyelinating pathologies (animal models and multiple sclerosis patients).

Based on the ihMT theory allowing to interpret the signal as a dipolar order effect within macromolecules, our group has demonstrated the possibility to measure T1D values in vivo in the central nervous system of both humans and small animals through the modification of the ihMT MRI sequence and an associated theoretical model (Varma et al, MRM 2016). The differences in T1D between tissues were further exploited through a mechanism that we called T1D-filtering to obtain more marked contrasts towards certain structures (Prevost et al, NMR biomed 2017). The dipolar relaxation constant is a parameter that depends both on the structure of the tissue and on the molecular dynamics. As various molecular motions exist in complex lipid-containing tissues such as myelin, the existence of several dipolar relaxation constants in time ranges spanning several decades has been observed. Using ihMT at high RF saturation power, we have demonstrated the existence of at least two T1D components in CNS tissues (rat spinal cord extracts) (Carvalho et al, JMR 2020): a long component in the order of ~10ms and a short one in the order of 500us. Regarding the origin of the ihMT signal, a study performed on transgenic mice (plp-GFP) comparing the ihMT signal to the Green fluorescence signal in different brain structures has validated the ihMT technique as sensitive to myelin (Duhamel et al, Neuroimage 2019). In terms of specificity, this study also showed differences depending on the strength of T1D filtering performed. More generally, the sensitivity of ihMT to several T1D components of different values raised questions about their association with different tissues of the central nervous system. In a more recent work, we demonstrated the possibility to derive high-pass and bandpass T1D filters using modified ihMT sequences that allow isolating long T1D components (>1ms) and short T1D components (<1ms) respectively (Hertanu et al, MRM 2022, part 1). The high correlation of long T1D components with myelin and the low correlation of short T1D component make ihMT high-pass T1D filters good myelin MRI biomarker candidates (Hertanu et al, MRM 2022, part 2).

An important discovery of a new sensitivity enhancement mechanism of the ihMT technique (Mchinda et al, MRM 2018, Varma et al, JMR 2018), patented in 2017 (PCT/EP2017/056978) eased the deployment of the ihMT technique for human studies. A patent maturation project consisting in a pilot clinical study at 1.5T, demonstrated the clinical added-value of the sensitivity-enhanced ihMT technology. Furthermore, the physical mechanisms of the sensitivity-enhanced ihMT approach were exploited to expand the ihMT sequences at higher magnetic field (3T), while insuring a good robustness and immunity to B₁⁺ inhomogeneities (Soustelle et al, MRM 2021).

In terms of applications, we have demonstrated the interest and advantage of the ihMT technique over other sensitive but less specific techniques in the characterization of demyelinating pathologies in humans (e.g., multiple sclerosis, van Obbberghen et al, AJNR 2018) and in animals (e.g., cuprizone model, Hertanu et al, Neuroimage 2022). Note also the interest for other applications in the neuroscience field, such as a more realistic mapping of cortical myeloachitecture obtained with ihMT as compared to T1w techniques (Munsch et al, Neuroimage 2021).

 

Collaborations

http://www.iecb.u-bordeaux.fr/index.php/en/equipes/170-solid-state-nmr-of-molecular-assemblies

Stem cells and brain repair

https://www.bidmc.org/research/research-by-department/radiology

 

Selected Publications

2022:

Hertanu, Andreea, Lucas Soustelle, Julie Buron, Julie Le Priellec, Myriam Cayre, Arnaud Le Troter, Valentin H. Prevost, et al. “Inhomogeneous Magnetization Transfer (IhMT) Imaging in the Acute Cuprizone Mouse Model of Demyelination/Remyelination.” NeuroImage, December 1, 2022, 119785. https://doi.org/10.1016/j.neuroimage.2022.119785.

Alsop, David C., Ece Ercan, Olivier M. Girard, Alex L. Mackay, Carl A. Michal, Gopal Varma, Elena Vinogradov, and Guillaume Duhamel. “Inhomogeneous Magnetization Transfer (IhMT) Imaging: Concepts and Directions for Further Development.” NMR in Biomedicine, August 2, 2022. https://doi.org/10.1002/nbm.4808. ⟨hal-03767121⟩

Hertanu, Andreea, Lucas Soustelle, Julie Buron, Julie Le Priellec, Myriam Cayre, et al. “T1D -Weighted IhMT Imaging – Part II. Investigating the Long- and Short-T1D Components Correlation with Myelin Content. Comparison with R1 and the Macromolecular Proton Fraction.” Magnetic Resonance in Medicine, January 9, 2022. https://doi.org/10.1002/mrm.29140. ⟨hal-03529600⟩

Hertanu, Andreea, Lucas Soustelle, Arnaud Le Troter, Julie Buron, Julie Le Priellec, et al. “T1D -Weighted IhMT Imaging – Part I. Isolation of Long- and Short-T1D Components by T1D -Filtering.” Magnetic Resonance in Medicine, January 17, 2022. https://doi.org/10.1002/mrm.29139. ⟨hal-03529187⟩

Soustelle, Lucas, Thomas Troalen, Andreea Hertanu, Samira Mchinda, Jean-Philippe Ranjeva, Maxime Guye, Gopal Varma, David C. Alsop, Guillaume Duhamel, and Olivier M. Girard. “A Strategy to Reduce the Sensitivity of Inhomogeneous Magnetization Transfer (IhMT) Imaging to Radiofrequency Transmit Field Variations at 3 T.” Magnetic Resonance in Medicine 87, no. 3 (2022): 1346–59. https://doi.org/10.1002/mrm.29055. ⟨hal-03429467⟩

2021:
Munsch, Fanny, Gopal Varma, Manuel Taso, Olivier Girard, Arnaud Guidon, et al. “Characterization of the Cortical Myeloarchitecture with Inhomogeneous Magnetization Transfer Imaging (IhMT).” NeuroImage 225 (January 15, 2021): 117442. https://doi.org/10.1016/j.neuroimage.2020.117442. ⟨hal-02985429⟩

2020:
Gopal Varma, Fanny Munsch, Brian Burns, Guillaume Duhamel, Olivier Girard, et al.. Three‐dimensional inhomogeneous magnetization transfer with rapid gradient‐echo (3D ihMTRAGE) imaging. Magnetic Resonance in Medicine, Wiley, 2020, ⟨10.1002/mrm.28324⟩ ⟨hal-02904183⟩

Victor N.D. Carvalho, Andreea Hertanu, Axelle Grélard, Samira Mchinda, Lucas Soustelle, et al.. MRI assessment of multiple dipolar relaxation time (T1D) components in biological tissues interpreted with a generalized inhomogeneous magnetization transfer (ihMT) model. Journal of Magnetic Resonance, Elsevier, 2020, 311, pp.106668. ⟨10.1016/j.jmr.2019.106668⟩ ⟨hal-02456394⟩

H. Rasoanandrianina, S. Demortière, A. Trabelsi, J.P. Ranjeva, O. Girard, et al.. Sensitivity of the Inhomogeneous Magnetization Transfer Imaging Technique to Spinal Cord Damage in Multiple Sclerosis. American Journal of Neuroradiology, American Society of Neuroradiology, 2020, 41 (5), pp.929-937. ⟨10.3174/ajnr.A6554⟩ ⟨hal-02869168⟩

2019:
G. Duhamel, V.H. Prevost, M. Cayre, A. Hertanu, S. Mchinda, et al.. Validating the sensitivity of inhomogeneous magnetization transfer (ihMT) MRI to myelin with fluorescence microscopy. NeuroImage, Elsevier, 2019, 199, pp.289-303. ⟨10.1016/j.neuroimage.2019.05.061⟩ ⟨hal-02156603⟩

2018:
G. Varma, O.M. Girard, S. Mchinda, V.H. Prevost, A.K. Grant, et al.. Low duty-cycle pulsed irradiation reduces magnetization transfer and increases the inhomogeneous magnetization transfer effect. Journal of Magnetic Resonance, Elsevier, 2018, 296, pp.60-71. ⟨10.1016/j.jmr.2018.08.004⟩ ⟨hal-02059549⟩

E. van Obberghen, S. Mchinda, A. Le Troter, V.H. Prevost, P. Viout, et al.. Evaluation of the Sensitivity of Inhomogeneous Magnetization Transfer (ihMT) MRI for Multiple Sclerosis. American Journal of Neuroradiology, American Society of Neuroradiology, 2018, 39 (4), pp.634-641. ⟨10.3174/ajnr.a5563⟩ ⟨hal-02156650⟩

2017:
Mchinda, Samira, Gopal Varma, Valentin H. Prevost, Arnaud Le Troter, Stanislas Rapacchi, Maxime Guye, Jean Pelletier, et al. “Whole Brain Inhomogeneous Magnetization Transfer (IhMT) Imaging: Sensitivity Enhancement within a Steady-State Gradient Echo Sequence.” Magnetic Resonance in Medicine 79, no. 5 (May 2018): 2607–19. https://doi.org/10.1002/mrm.26907. ⟨hal-01657938⟩

V. H. Prevost, O. M. Girard, S. Mchinda, G. Varma, D. C. Alsop, et al.. Optimization of inhomogeneous magnetization transfer (ihMT) MRI contrast for preclinical studies using dipolar relaxation time (T1D) filtering. NMR in Biomedicine, Wiley, 2017, 30 (6), ⟨10.1002/nbm.3706⟩ ⟨hal-01657969⟩

Henitsoa Rasoanandrianina, Aude-Marie Grapperon, Manuel Taso, Olivier M. Girard, Guillaume Duhamel, et al.. Region-specific impairment of the cervical spinal cord (SC) in amyotrophic lateral sclerosis: A preliminary study using SC templates and quantitative MRI (diffusion tensor imaging/inhomogeneous magnetization transfer). NMR in Biomedicine, Wiley, 2017, 30 (12), pp.e3801. ⟨10.1002/nbm.3801⟩ ⟨hal-01657945⟩

2016:
Gopal Varma, Olivier M. Girard, Valentin H. Prevost, Aaron K. Grant, Guillaume Duhamel, et al.. 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, Wiley, 2016, ⟨10.1002/mrm.26523⟩ ⟨hal-01425505⟩

Olivier M. Girard, Virginie Callot, Valentin H. Prevost, Benjamin Robert, Manuel Taso, et al.. Magnetization transfer from inhomogeneously broadened lines (ihMT): Improved imaging strategy for spinal cord applications. Magnetic Resonance in Medicine, Wiley, 2016, pp.n/a–n/a. ⟨10.1002/mrm.26134⟩ ⟨hal-01425518⟩

Valentin H. Prevost, Olivier M. Girard, Gopal Varma, David C. Alsop, Guillaume Duhamel. 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.), 2016, 29 (4), pp.699–709. ⟨10.1007/s10334-015-0523-2⟩ ⟨hal-01425510⟩

Manuel Taso, Olivier M. Girard, Guillaume Duhamel, Arnaud Le Troter, Thorsten Feiweier, et al.. 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, Wiley, 2016, 29 (6), pp.817–832. ⟨10.1002/nbm.3530⟩ ⟨hal-01425521⟩

2015:
G. Varma, Olivier Girard, Valentin Prevost, A. K. Grant, Guillaume Duhamel, et al.. 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), 2015, 260, pp.67–76. ⟨10.1016/j.jmr.2015.08.024⟩ ⟨hal-01414326⟩

Olivier M. Girard, Valentin H. Prevost, Gopal Varma, Patrick J. Cozzone, David C. Alsop, et al.. Magnetization transfer from inhomogeneously broadened lines (ihMT): Experimental optimization of saturation parameters for human brain imaging at 1.5 Tesla. Magnetic Resonance in Medicine, Wiley, 2015, 73 (6), pp.2111–2121. ⟨10.1002/mrm.25330⟩ ⟨hal-01414354⟩

Gopal Varma, Guillaume Duhamel, Cedric Bazelaire, David C. Alsop. Magnetization transfer from inhomogeneously broadened lines: A potential marker for myelin. Magnetic Resonance in Medicine, Wiley, 2015, 73 (2), pp.614–622. ⟨10.1002/mrm.25174⟩ ⟨hal-01414328⟩