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Purpose: To provide real-time quantitative organ-specific information - specifically placental and brain T2* - to allow optimization of the MR examination to the individual patient. Methods: A FIRE-based real-time setup segmenting placenta and fetal brain in real-time, performing T2* fitting and analysis and calculation of the centile was implemented. A nn-UNet were trained and tested on 2989 datasets for the fetal brain and a second one trained on 210 datasets for the placenta for automatic segmentation. T2* normal curves were obtained from 106 cases and prospective evaluation was performed on 10 cases between 35 and 39 weeks GA. Results: Quantitative brain and placental T2* maps and centiles were available in all prospective cases within 30 seconds. The robustness of the method was shown with intra-scan repeats (mean difference 1.04+/-12.39 ms for fetal brain and -3.15+/-8.88 ms for placenta) and direct validation with vendor-processed offline results (mean difference 1.62+/-4.33 ms for fetal brain and 0.16+/-6.19 ms for placenta). Discussion and Conclusion: Real-time available organ-specific quantitative information enables more personalized MR examinations, selection of the most pertinent sequences and thus the promise of reduced recalls and specific insights into tissue properties. The here enabled placental T2*, demonstrated in multiple recent studies to be a biomarker sensitive to a range of pregnancy complications, and fetal brain T2* will be explored in further studies in pregnancies with pre-eclampsia, growth restriction as a way of enabling future MR-guided fetal interventions.

MRI systems are traditionally engineered to produce close to idealized performance, enabling a simplified pulse sequence design philosophy. An example of this is control of eddy currents produced by gradient fields; usually these are compensated by pre-emphasizing demanded waveforms. This process typically happens invisibly to the pulse designer, allowing them to assume the achieved gradient waveform will be as desired. Whilst convenient, this imposes stricter limits on the sequence design than the hardware can handle (for example, pre-emphasis adds an additional overhead to amplifiers). This strategy can be undesirable particularly for lower performance or resource-limited hardware. Instead we explore the use of a 'digital twin' (i.e. an end-to-end model of the scanner system) to optimize control inputs, resulting in sequences that inherently compensate for known imperfections. We explore digital twin optimization specifically for gradient system imperfections as an exemplar. This is first explored in simulations using a simple exponential eddy current model, then experimentally using an empirical gradient impulse response function on a 7T MRI system. When unconstrained, digital twin optimization reproduces classic pre-emphasis. When strict hardware constraints are imposed (simulating lower performance hardware), it identifies novel sequences for scenarios where classic pre-emphasis would be unachievable. Experimentally, the optimization approach was demonstrated to substantially reduce ghosting effects in echo planar images on a 7T system. Digital twin optimization may allow more efficient use of hardware by taking a whole system approach. Ultimately this could enable the use of cheaper hardware without loss of performance., Comment: 33 pages, 14 figures (including supporting information)

Purpose: This work proposes a novel RF pulse design for parallel transmit (pTx) systems to obtain uniform saturation of semisolid magnetization for Magnetization Transfer (MT) contrast in the presence of transmit field ($B_1^+$) inhomogeneities. The semisolid magnetization is usually modeled as being purely longitudinal, with the applied $B_1^+$ field saturating but not rotating its magnetization, thus standard pTx pulse design methods do not apply. Theory and Methods: Pulse design for Saturation Homogeneity (PUSH) optimizes pTx RF pulses by considering uniformity of root-mean squared $B_1^+$, $B_1^{rms}$, which relates to the rate of semisolid saturation. Here we considered designs consisting of a small number of spatially non-selective sub-pulses optimized over either a single 2D plane or 3D. Simulations and in vivo experiments on a 7T Terra system with an 8-TX Nova head coil in 5 subjects were carried out to study the homogenization of $B_1^{rms}$ and of the MT contrast by acquiring MT ratio maps. Results: Simulations and in vivo experiments showed up to 6 and 2 times more uniform $B_1^{rms}$ compared to circular polarized (CP) mode for 2D and 3D optimizations, respectively. This translated into 4 and 1.25 times more uniform MT contrast, consistently for all subjects, where 2 sub-pulses were enough for the implementation and coil used. Conclusion: The proposed PUSH method obtains more uniform and higher MT contrast than CP mode within the same SAR budget., Comment: 18 pages, 9 figures. Code available at: https://github.com/mriphysics/PUSH

Purpose: Universal Pulses (UPs) are excitation pulses that reduce the flip angle inhomogeneity in high field MRI systems without subject-specific optimization, originally developed for parallel transmit (PTX) systems at 7T. We investigated the potential benefits of UPs for single channel (SC) transmit systems at 3T, which are widely used for clinical and research imaging, and for which flip angle inhomogeneity can still be problematic. Methods: SC-UPs were designed using a spiral nonselective k-space trajectory for brain imaging at 3T using transmit field maps (B1+) and off-resonance maps (B0) acquired on two different scanner types: a 'standard' single channel transmit system and a system with a PTX body coil. The effect of training group size was investigated using data (200 subjects) from the standard system. The PTX system was used to compare SC-UPs to PTX-UPs (15 subjects). In two additional subjects, prospective imaging using SC-UP was studied. Results: Average flip angle error fell from 9.5+/-0.5% for 'default' excitation to 3.0+/-0.6% using SC-UPs trained over 50 subjects. Performance of the UPs was found to steadily improve as training group size increased, but stabilized after ~15 subjects. On the PTX-enabled system, SC-UPs again outperformed default excitation in simulations (4.8+/-0.6% error versus 10.6+/-0.8% respectively) though greater homogenization could be achieved with PTX-UPs (3.9+/-0.6%) and personalized pulses (SC-PP 3.6+/-1.0%, PTX-PP 2.9+/-0.6%). MP-RAGE imaging using SC-UP resulted in greater separation between grey and white matter signal intensities than default excitation. Conclusions: SC-UPs can improve excitation homogeneity in standard 3T systems without further calibration and could be used instead of a default excitation pulse for nonselective neuroimaging at 3T., Comment: Submitted to Magnetic Resonance Imaging

Purpose: Magnetization transfer (MT) and inhomogeneous MT (ihMT) contrasts are used in MRI to provide information about macromolecular tissue content. In particular, MT is sensitive to macromolecules and ihMT appears to be specific to myelinated tissue. This study proposes a technique to characterize MT and ihMT properties from a single acquisition, producing both semiquantitative contrast ratios, and quantitative parameter maps. Theory and Methods: Building upon previous work that uses multiband radiofrequency (RF) pulses to efficiently generate ihMT contrast, we propose a cyclic-steady-state approach that cycles between multiband and single-band pulses to boost the achieved contrast. Resultant time-variable signals are reminiscent of a magnetic resonance fingerprinting (MRF) acquisition, except that the signal fluctuations are entirely mediated by magnetization transfer effects. A dictionary-based low-rank inversion method is used to reconstruct the resulting images and to produce both semiquantitative MT ratio (MTR) and ihMT ratio (ihMTR) maps, as well as quantitative parameter estimates corresponding to an ihMT tissue model. Results: Phantom and in vivo brain data acquired at 1.5T demonstrate the expected contrast trends, with ihMTR maps showing contrast more specific to white matter (WM), as has been reported by others. Quantitative estimation of semisolid fraction and dipolar T1 was also possible and yielded measurements consistent with literature values in the brain. Conclusions: By cycling between multiband and single-band pulses, an entirely magnetization transfer mediated 'fingerprinting' method was demonstrated. This proof-of-concept approach can be used to generate semiquantitative maps and quantitatively estimate some macromolecular specific tissue parameters., Comment: 34 Pages and 15 Figures (Including Supporting Information), Submitted to Magnetic Resonance in Medicine (MRM). Updated to include link to final published article

This study presents a comparison of quantitative MRI methods based on an efficiency metric that quantifies their intrinsic ability to extract information about tissue parameters. Under a regime of unbiased parameter estimates, an intrinsic efficiency metric $\eta$ was derived for fully-sampled experiments which can be used to both optimize and compare sequences. Here we optimize and compare several steady-state and transient gradient-echo based qMRI methods, such as magnetic resonance fingerprinting (MRF), for joint T1 and T2 mapping. The impact of undersampling was also evaluated, assuming incoherent aliasing that is treated as noise by parameter estimation. In-vivo validation of the efficiency metric was also performed. Transient methods such as MRF can be up to 3.5 times more efficient than steady-state methods, when spatial undersampling is ignored. If incoherent aliasing is treated as noise during least-squares parameter estimation, the efficiency is reduced in proportion to the SNR of the data, with reduction factors of 5 often seen for practical SNR levels. In-vivo validation showed a very good agreement between the theoretical and experimentally predicted efficiency. This work presents and validates an efficiency metric to optimize and compare the performance of qMRI methods. Transient methods were found to be intrinsically more efficient than steady-state methods, however the effect of spatial undersampling can significantly erode this advantage., Comment: Submitted to Physics in Medicine and Biology

Purpose: To develop a MRI acquisition and reconstruction framework for volumetric cine visualisation of the fetal heart and great vessels in the presence of maternal and fetal motion. Methods: Four-dimensional depiction was achieved using a highly-accelerated multi-planar real-time balanced steady state free precession acquisition combined with retrospective image-domain techniques for motion correction, cardiac synchronisation and outlier rejection. The framework was evaluated and optimised using a numerical phantom, and evaluated in a study of 20 mid- to late-gestational age human fetal subjects. Reconstructed cine volumes were evaluated by experienced cardiologists and compared with matched ultrasound. A preliminary assessment of flow-sensitive reconstruction using the velocity information encoded in the phase of dynamic images is included. Results: Reconstructed cine volumes could be visualised in any 2D plane without the need for highly-specific scan plane prescription prior to acquisition or for maternal breath hold to minimise motion. Reconstruction was fully automated aside from user-specified masks of the fetal heart and chest. The framework proved robust when applied to fetal data and simulations confirmed that spatial and temporal features could be reliably recovered. Expert evaluation suggested the reconstructed volumes can be used for comprehensive assessment of the fetal heart, either as an adjunct to ultrasound or in combination with other MRI techniques. Conclusion: The proposed methods show promise as a framework for motion-compensated 4D assessment of the fetal heart and great vessels.

An Extended Phase Graph framework for modelling systems with exchange or magnetization transfer (MT) is proposed. The framework, referred to as EPG-X, models coupled two-compartment systems by describing each compartment with separate phase graphs that exchange during evolution periods. There are two variants: EPG-X(BM) for systems governed by the Bloch-McConnell equations; and EPG-X(MT) for the pulsed MT formalism. For the MT case the "bound" protons have no transverse components so their phase graph consists only longitudinal states. EPG-X was used to model steady-state gradient echo imaging, MT effects in multislice Turbo Spin Echo imaging, multiecho CPMG for multicomponent T2 relaxometry and transient variable flip angle gradient echo imaging of the type used for MR Fingerprinting. Experimental data were also collected for the final case. Steady-state predictions from EPG-X closely match directly derived steady-state solutions which differ substantially from classic "single pool" EPG predictions. EPG-X(MT) predicts similar MT related levels of signal attenuation in white matter as have been reported elsewhere in the literature. Modelling of CPMG echo trains with EPG-X(BM) suggests that exchange processes can lead to an underestimate of the fraction of short T2 species. Modelling of transient gradient echo sequences with EPG-X(MT) suggests that measurable MT effects result from variable saturation of bound protons, particularly after inversion pulses. In conclusion, EPG-X can be used for modelling of the transient signal response of systems exhibiting chemical exchange or MT. This may be particularly beneficial for relaxometry approaches that rely on characterising transient rather than steady-state sequences., Comment: For associated code see https://github.com/mriphysics/EPG-X