3569

BTX: Simultaneous 3D Quantitative Magnetization Transfer Imaging and Susceptibility Mapping

Albert Jang^1,2, Hyungseok Jang³, and Fang Liu^1,2
¹Athinoula A. Martinos Center for Biomedical Imaging, Harvard Medical School, Charlestown, MA, United States, ²Radiology, Massachusetts General Hospital, Boston, MA, United States, ³Radiology, University of California, San Diego, San Diego, CA, United States

Synopsis

Keywords: Quantitative Imaging, Multi-Contrast, Magnetization Transfer, Quantitative Susceptibility Mapping

We propose a novel sequence that enables simultaneous quantitative magnetization transfer (qMT) imaging and susceptibility mapping (QSM) for assessing tissue composition, microstructure, and microenvironment. We extend our BTS sequence to incorporate a multi-echo acquisition scheme for probing tissue susceptibility information. The acquisition allows quantification of B₁⁺, bias-corrected T₁, qMT parameters (macromolecule bound proton fraction and proton exchange rate), tissue susceptibility and T₂^*. The method’s feasibility is demonstrated using an in-vivo brain scan, where 3D concurrent qMT and QSM were obtained for the whole brain at feasible scan time.

Introduction

Both quantitative magnetization transfer (qMT) imaging¹ and susceptibility mapping (QSM)² can provide promising imaging biomarkers for evaluating tissue pathogenesis in neural^3,4, cardiac^5,6, body^7,8 and musculoskeletal diseases^9,10. While each technique utilizes separate modeling of MR signal magnitude (for qMT) and phase (for QSM) to obtain subsequent quantitative information, there has not been a single acquisition strategy and modeling technique that can assess both in a unified framework. Measuring qMT and QSM simultaneously has not yet been well-established in applications such as multiple sclerosis and osteoarthritis assessment in the brain and knee. Recently, we proposed a new method BTS¹¹ (Bloch-Siegert and magnetization Transfer Simultaneously) for qMT imaging using a spoiled gradient-echo sequence with off-resonance RFs to model Bloch-Siegert¹² shift (for B₁⁺ correction) and MT¹³. In this work, we extend our method (denoted BTX) to incorporate a multi-echo acquisition for obtaining QSM parameters. This new sequence, in conjunction with our modeling technique, leverages both the magnitude and phase of the acquired MR signals, enabling simultaneous qMT and QSM at no cost in additional scan time.

Theory

BTS: The original BTS sequence is implemented on a spoiled gradient-echo scheme where an off-resonance RF is introduced between excitation and acquisition (FIG1A). This induces two independent effects: 1) MT through direct saturation of macromolecules and 2) B₁⁺-dependent Bloch-Siegert phase shift of free water proton. The BTS term in FIG3A gives the resulting analytical signal equation. Using a variable flip-angle (vFA) scheme with (BTS) and without (baseline) off-resonance RF applied, this signal term is used to generate B₁⁺ and T₁^F (MT-corrected T₁ for free water) maps and MT parameter (macromolecule proton fraction f and exchange rate k_F) maps. New BTX: Our proposed BTX (BTS with susceptibility mapping) utilizes the idle time between excitation and acquisition for a multi-echo acquisition module (FIG1A). This enables T₂^* quantification via magnitude decay and magnetic susceptibility (χ) quantification via spin phase evolution governed by the additional T₂^* and QSM terms in FIG3A. As a result, this unified sequence and modeling allows quantification of B₁⁺ (for flip-angle correction), free water T₁^F, MT parameters f and k_F, tissue susceptibility χ and T₂^*, concurrently, at no additional scan time.

Methods

An in-vivo experiment was conducted to scan the whole sagittal brain of a healthy volunteer using a 32-channel head coil on a 3T scanner (Siemens Prisma). Sequence parameters include: field of view = 23x23x16cm³, matrix size = 174x176x80, slice thickness = 2mm, number of slices = 80, total 6 TEs spanning 11ms to 36ms with 5ms echo spacing, TR = 40ms. Multiple scans were acquired at varying prescribed flip-angles of 5˚, 20˚ and 40˚, with an 8ms fermi pulse at off-resonance frequency 4kHz and effective flip-angle 629˚ used for off-resonance saturation, turned on and off. An additional acquisition at flip-angle 20˚ with off-resonance frequency -4kHz was also acquired for B₁⁺ map estimation using the Bloch-Siegert method¹². Utility of signal magnitude: The magnitude of MR signals and actual flip-angles extracted from B₁⁺ maps were then fit into the BTX model to generate T₁^F, f and k_F (FIG3B) under the assumption of fixed MT properties for macromolecule bound proton T₁^R = 1s, T₂^R = 12μs and a Super-Lorentzian MT saturation line shape¹⁴. T₂^* was also estimated by fitting an exponential decay as a function of TEs (FIG3D). Utility of signal phase: The phase of MR signals at multiple echoes was used to estimate the total field¹⁵, which was subsequently used in projection onto dipole (PDF)¹⁶ method to remove the background field. The estimated tissue field was then used to estimate susceptibility χ using morphology-enabled dipole inversion (MEDI)¹⁷ (FIG3C). Inter-scan motion was compensated using a co-registration method¹⁸ and images were reformatted into axial view to better represent all maps in the thalamus brain region.

Results and Discussion

Quantitative MT (FIG4A-C), B₁⁺ (FIG4D), QSM (FIG4E) and T₂^* (FIG4F) maps of the in-vivo brain measured concurrently are presented. T₁^F, MT parameters f and k_F, magnetic susceptibility χ and T₂^* were measured in the white matter and gray matter ROI regions indicated by the numbered white and black arrows in FIG4A, and the caudate and putamen region indicated by the numbered orange and blue arrows in FIG4E. T₁^F, f, k_F, χ and T₂^* for white matter (1): 0.992[s]/1.158[s]/15.0[%]/1.63[s^-1]/-19.7[ppb]/45[ms]; gray matter (2): 1.231[s]/1.432[s]/11.2[%]/1.2[s^-1]/16.2[ppb]/37[ms]; caudate (3): 1.597[s]/1.843[s]/7.8[%]/0.9[s^-1]/74.3[ppb]/41.6[ms]; putamen (4):1.415[s]/1.550[s]/6.7[%]/1.7[s^-1]/74.3[ppb]/38.6[ms]. Measured values correspond with values reported in literature^1,19.

Conclusion

BTX, a new unified sequence and modeling technique that simultaneously provides magnetization transfer and susceptibility quantification, has been proposed. Simultaneous estimation of B₁⁺ for compensation, free water T₁^F, MT parameters (f and k_F) reflecting macromolecule content, magnetic susceptibility χ and T₂^* was demonstrated in-vivo brain, showing great agreements with reported values from separate qMT and QSM experiments^1,19. The ability to simultaneously obtain qMT and QSM biomarkers can provide complementary information to facilitate assessment of tissue composition, microstructure, and microenvironment in multiple sclerosis with myelin damage and iron deposition in the brain, and osteoarthritis with cartilage extracellular matrix degeneration and microcalcification in the joint. As a result, our proposed method will provide powerful tools for improving the understanding of complex pathophysiology in various neural, cardiac, body and musculoskeletal diseases.

Acknowledgements

We thank the funding support from NIBIB R21EB031185, NIAMS R01AR079442, R01AR081344 and R01AR078877.

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Figures

FIG 1. (a) Unified sequence that encodes both MT and χ. The idle time of the BTS sequence is utilized for multi-echo acquisition, enabling quantification of χ and T₂^* in addition to B₁⁺ and MT parameters T₁^F, f and k_F. (b) In the steady-state, M_z^R decreases while M_xy^F gains a B₁⁺-dependent phase from off-resonance irradiation. During multi-echo acquisition, M_xy^F accrues additional phase along with magnitude decay.

FIG 2. The binary spin-bath system is governed by the Bloch-McConnell equations. If the frequency of the off-resonance irradiation is significantly larger than its peak amplitude and Larmor frequency (ω_off ≫ ω₁^max, ω_o), the equations can be solved in the steady-state to derive the BTX signal equation shown above. α is excitation flip angle, ω₁(t) is time-dependent RF amplitude, and W(Δ=0, t) and W(Δ=Δ_off, t) are the on-resonance and off-resonance time-dependent saturation rates of the macromolecule pool.

FIG 3. (a) BTX signal equation (S_BTX), constants given in FIG2. (b) B₁⁺ is calculated using the phase of the BTS term, which is used to calculate the actual applied FAs to estimate T₁^F and MT parameters (f and k_F) using the magnitude of the BTS term. (c) Phases of the multi-echo acquisition (QSM term) is used to estimate total field¹⁵, which is then applied to remove background field¹⁶. The estimated tissue field is used to estimate χ¹⁷. (d) T₂^* is estimated by fitting signal magnitudes (T₂^* term) to an exponential decay as a function of TE. Superscript Rx denotes prescribed FA.

FIG 4. (a) Free water spin-lattice relaxation constant T₁^F, (b) macromolecule proton fraction f, (c) exchange rate k_F, (d) relative transmit field B₁⁺, (e) magnetic susceptibility χ and (f) T₂^* maps measured simultaneously from the unified sequence and modeling of BTX. Measurement values reported in the Results and Discussions section correspond well with literature values.

Proc. Intl. Soc. Mag. Reson. Med. 31 (2023)

3569

DOI: https://doi.org/10.58530/2023/3569