Researchers and clinicians interested in quantitative magnetization transfer, bound pool mapping and white matter demyelination.The bound pool fraction (BPF) is a fundamental parameter of the two-pool model¹ and reflects the relative pool size of bound protons involved in magnetization transfer (MT). Since the bound proton pool in brain tissue has been associated with myelin, the BPF has been proposed as a quantitative marker for myelin². Quantitative MT sequences which have been proposed so far are based either on a steady state approach (with off-resonance pulsed irradiation³ using a time-varying irradiation model or continuous wave mode^4,5) or on a transient approach by following the fast MT-induced recovery of the magnetization⁶. We here present a proof of concept for a new BPF mapping sequence. The new approach is based on the observation that the signal intensity in a STEAM sequence decays double-exponentially due to MT^7,8. With the help of a T1 map, a single acquisition with just one mixing time (TM) and an integrated spin echo allows to map the BPF.

The slice selective STEAM experiment was implemented on a 3T PRISMA (Siemens Healthcare, Erlangen, Germany) using three slice-selective sinc-shaped 90° pulses and three modulation gradients in the slice selective direction (figure 1). A spin echo was acquired 10 ms after the second RF pulse and a stimulated echo was acquired 110ms after the third RF pulse. Other sequence parameters were: TR=900ms, 20 channel head coil, FOV=256mm, in plane resolution=0.5x0.5mm, acquisition time 4.47min. To prevent any remaining transversal coherences, crusher gradients were placed after each readout. T1 mapping was performed with an inversion recovery sequence with a turbo spin echo readout and following inversion times: 100ms, 200ms, 400ms, 800ms, 1600ms and 3200ms. We validated the sequence on a phantom with different concentrations of cross-linked bovine serum albumin probes (BSA) at room temperature and we performed ROI-based mean values. To calculate the BPF, first we evaluated the biexponential decay (figure 2) of the labeled magnetization (equation 1) at TM=100ms, where the component of the fast rate ($$$\lambda_1$$$) is vanished and the equation is only dependent on the slow rate $$$\lambda_2$$$ (corresponding to the apparent T1) (equation 2). Solving the monoexponential decay yields to $$$S_0/(f+1)$$$ and with $$$S_0$$$ from the SE, to the determination of f and consequently BPF $$$\left(f/(f+1)\right)$$$.

Equation 1: $$ S(\mbox{TM}) = S_0\frac{1}{f+1}\left(f e^{-\lambda_1~TM} + e^{-\lambda_2 ~TM}\right)$$

Equation 2: $$ S(\mbox{TM}) = S_0\frac{1}{f+1}e^{-\lambda_2 ~TM}$$Within our validation of the sequence with the BSA probes we have observed a high linearity between the measured BPF values and the concentrations of the BSA phantom. The measured BPF values ranged from 6.4% to 9.7% and are visualized in figure 3. The regression coefficient of the linear fit yields a value nearly to 1 (R2=0.9998).The proposed method shows the proof of concept for a new quantitative MT approach and it’s validation within BSA probes. The features of these sequence are the simplicity of calculating the BPF and the measurement of the initial labeled signal. Additionally, as the sequence is TR invariant, also TR near to the TM are possible. As the sequence is a low-SAR approach, it has also potential for high field applications. The limitations are that the scan time will be increased by the additional T1 and in the case of large B1 variations also a B1 map is needed. However, by using interleaved measurements, full brain coverage within 10 minutes are reasonable.