Gopal Varma^{1}, Fanny Munsch^{1}, Olivier M Girard^{2}, Guillaume Duhamel^{2}, and David C Alsop^{1}

Standard MT and ihMT ratio (ihMTR) measures can be sensitive to B_{1 }and T_{1}, making them less specific to tissue microstructure. Using the inverse signal, i.e. one divided by the signal, and a high flip-angle reference image in calculation of an ihMTR metric has been proposed as a metric with improved insensitivity to T_{1} and B_{1} in steady-state gradient-echo sequences. We present a modified method for use in prepared sequences such as magnetization prepared rapid gradient echo (MPRAGE). The sensitivity of ihMT MPRAGE metrics to T_{1} and B_{1} was tested using simulations and acquisitions in brains of healthy volunteers.

The inhomogeneous magnetization transfer (ihMT) signal can be used to characterize myelinated tissues and extract information on dipolar order^{1}. IhMT sensitive images can be acquired either by interleaving RF irradiation into a stead-state acquisition^{2}, e.g. spoiled gradient echo (SPGR)^{3}, or by applying irradiation in a preparation module prior to acquisition^{4}, such as magnetization prepared rapid gradient echo acquisition^{5 }(MPRAGE) (Fig. 1a). IhMT prepared MPRAGE (or ihMTRAGE) can utilize the low duty cycle preparation that increases the ihMT signal while maintaining or lowering specific absorption rates^{4}.

The approach to quantifying ihMT can affect its specificity and sensitivity. The ratio of the ihMT signal over that with no MT preparation, i.e. ihMTR, provides a semi-quantitative metric (Fig. 2a), but is dependent on a combination of quantitative parameters^{1}. Use of the inverse ihMT signal along with a high flip-angle (FA) reference in a steady-state ihMT sequence has been proposed as a more B_{1 }and T_{1} independent measure^{3,6}. The B_{1} independence depends on a linear relationship of the inverse subtraction with power, as achieved in low duty cycle preparations^{4}. In this work, we demonstrate the (in)dependence of the ihMTRAGE sequence to T_{1 }and B_{1} using the inverse ihMT signal multiplied by a reference acquisition with an SPGR like preparation. We carry out simulations and in vivo experiments to study the combination of the inverse ihMT signal with an SPGR preparation before the MPRAGE acquisition to mimic a high FA reference.

The MT preparation for ihMTRAGE consisted of 5ms pulses (rectangular/trapezoid-like for simulations/experiments) repeated ten times (every 100ms for 1s), with peak B_{1} of 14μT (for single frequency RF irradiation at off-resonance Δ) (Fig. 1a). The SPGR-like module consisted of RF-spoiled on-resonance pulses with a 25ms repetition time (TR) applied 40 times over 1s (Fig. 1b). Several FAs for the on-resonance pulses were evaluated. An adiabatic spectrally selective inversion (ASPIR) pulse was also included in the last TR of the reference to mitigate fat signal contamination in the reference. IhMT signals were simulated using numerical integration of the differential equations associated with a model for ihMT, and parameters based on white matter (WM)^{4}.

All experiments were carried out on a 3T scanner with a 32-channel receive coil. Data were collected from the brains of healthy volunteers (n=5). IhMTR and inverse ihMT, ihMTR_{inv,θ }metrics were calculated (Figs. 2a-b). Acquisition of high FA SPGR-like preparations with two FAs (25° and 45°) along with the zero power reference allowed construction of a pseudo-T_{1 }map^{7}. B_{1 }mapping was conducted based on the Bloch-Siegert shift^{8 }and calculated as the ratio of the actual FA to that prescribed.

Simulations provide a guide as to the response of the ihMT signal metrics to variations in parameters. Both ihMTR and the inverse ihMT signal show an increase with B_{1 }and T_{1 }(Figs. 3a-b). Multiplication of the inverse ihMT by the signal from SPGR-like preparations (Fig. 2b) compensates for changes in simulated T_{1}. The sensitivity of ihMTR_{inv,θ }to B_{1} was dependent on FA (Figs. 3c-d): IhMTR_{inv,45° }showed good insensitivity around the nominal B_{1}. IhMTR_{inv,25°} showed insensitivity to increases in B_{1}, but greater sensitivity to decreases in B_{1} than ihMTR_{inv,45°}.

IhMTRAGE data were of good image quality but ihMTR_{inv,45°} images appeared noisier than ihMTR_{inv,25°} (Figs. 4b-c). This is a result of the low signal from extreme T_{1} weighting of the 45° reference data. Both ihMTR_{inv} metrics showed greater insensitivity to the variation in B_{1} in WM, with a variance divided by the mean value across manually selected WM regions in all subjects of 3x10^{-4}, compared with 4x10^{-3} for ihMTR (Figs. 4d-f). WM in and around the CC only was used to assess the effect of T_{1} variation to limit contribution from B_{1} inhomogeneity (Figs. 5a-c). IhMTR_{inv,25°} provided the smallest variance divided by mean value of 7x10^{-4}. A negative correlation was observed between T_{1} and all three ihMT metrics (Figs. 5d-f), which was strongest for ihMTR_{inv,45°}. The implications of this correlation are uncertain, since higher myelin density should decrease T_{1} and increase ihMT measures.

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