Methods for T1 & T1rho Mapping
1École Polytechnique, University of Montréal, Montréal, QC, Canada
Synopsis
With advances in hardware and the growing availability
of post-processing tools, it is becoming easier and faster to obtain accurate T1 and T1ρ maps in clinically feasible times. This course shines a light on the
three basic types of T1 mapping techniques, exemplified by inversion recovery, variable flip angle, and MP2RAGE. The course will also introduce
techniques for quantitative mapping of the spin-locked relaxation time (T1ρ). T1ρ is closely related to both T1 and T2, but sensitive to different properties of
the tissue, and has therefore garnered interest in specialized applications (e.g., cartilage imaging).
Interactive tutorial available at: http://qmrlab.org/t1_book
Unboxing T1 mapping
T1 mapping dates back to the earliest NMR experiments, and it is still a vibrant and relevant field. With advances in hardware and the growing availability of post-processing tools, it is becoming easier and faster to obtain accurate T1 and T1ρ maps in clinically feasible times. This course shines a light on the three basic types of T1 mapping techniques, exemplified by inversion recovery, variable flip angle, and MP2RAGE. The course will also introduce techniques for quantitative mapping of the spin-locked relaxation (T1ρ). T1ρ is closely related to both T1 and T2, but sensitive to different properties of the tissue, and has therefore garnered interest in specialized applications (e.g., cartilage imaging).For more details and interactive figures visit the qMRLab blog:
http://qmrlab.org/t1_book
Inversion recovery
Widely considered the gold-standard for T1 mapping on an MRI system, the inversion recovery technique estimates T1 values by fitting the signal recovery curve acquired at different delays after an inversion (180) pulse. In a typical inversion recovery experiment (Fig. 1), the magnetization at thermal equilibrium is inverted using a 180degree RF pulse. After the longitudinal magnetization recovers through spin-lattice relaxation for a predetermined delay (inversion time, TI), a 90degree excitation pulse is applied, followed by a readout imaging sequence (typically a spin echo or gradient echo readout) to create a snapshot of the longitudinal magnetization state at that TI.Inversion recovery was first developed for nuclear magnetic resonance (NMR) in the 1940s [1,2], and the first T1 map was acquired using a saturation recovery technique (90as a preparation pulse instead of 180) [3]. NMR systems have higher signal-to-noise ratio, have precise phase data, and the measurement errors are more easily understood [4]; for this reason, NMR inversion recovery is more accurate than MRI measurements. Some distinct advantages of inversion recovery are its large dynamic range of signal change and an insensitivity to pulse sequence parameter imperfections [5]. Despite its proven robustness at measuring T1, inversion recovery is scarcely used in practice, because conventional implementations require repetition times (TRs) on the order of 2–5 times the longest T1 value in the system [6], making it challenging to acquire whole-organ T1 maps in a clinically feasible time. Nonetheless, it is continuously used as a reference measurement during the development of new techniques, or when comparing different T1 mapping techniques. Moreover, several variations of the inversion recovery technique have been developed, making it practical for some applications [7,8].
The conventional inversion recovery experiment is considered the gold-standard for T1 mapping. A typical protocol has a long TR value and a sufficient number of inversion times for stable fitting (typically five or more) covering the range [0, TR]. It offers a wide dynamic range of signals, allowing a number of inversion times where high SNR is available to sample the signal recovery curve [9]. T1 maps produced by inversion recovery are largely insensitive to inaccuracies in excitation flip angles and imperfect spoiling [5], as all parameters except TI are constant for each measurement and only a single acquisition is performed (at TI) during each TR. One important pulse sequence design consideration is to avoid acquiring data at inversion times where the signal for T1 values of the tissue-of-interest is nulled, as the magnitude images at this TI time will be dominated by Rician noise that can negatively impact the fit under low SNR conditions.
Despite its widely acknowledged robustness and accuracy, inversion recovery is not often used for in vivo studies. An important drawback of this technique is the need for long TR values, typically on the order of a few times the T1 value for general models, and up to 5xT1 for long TR approximated models. It takes about 5–20 mins to acquire a single-slice T1 map using the inversion recovery technique, as only one TI is acquired per TR, and the use of conventional Cartesian readouts enables only one phase encode line to be collected per excitation.
Nonetheless, the inversion recovery approach is indispensable as a reference measurement for comparisons against other T1 mapping methods, or to acquire a single-slice T1 map of a tissue to get T1 measurements for optimization of other pulse sequences.
NOTE: For in-depth coverage and more interactive content, please visit:
https://qmrlab.org/jekyll/2018/10/23/T1-mapping-inversion-recovery.html
Variable Flip Angle (VFA)
Variable flip angle (VFA) T1 mapping [10–12], also known as driven equilibrium single pulse observation of T1 (DESPOT1) [13,14], is a rapid quantitative T1 measurement technique that is widely used to acquire 3D T1 maps (e.g., whole-brain) in a clinically feasible time. VFA is used to estimate T1 values by acquiring multiple spoiled gradient echo acquisitions, each with different excitation flip angles. This pulse sequence (Fig. 2) uses very short TRs (on the order of 10 ms) and is sensitive to T1 values for a wide range of flip angles. VFA is a technique that originates from the NMR field, and was adopted because of its time efficiency and the ability to acquire accurate T1 values simultaneously for a wide range of values [10,12].For imaging applications, VFA also benefits from an increase in SNR because it can be acquired using a 3D acquisition instead of a multislice measurement, which also helps to reduce slice profile effects. One important drawback of VFA for T1 mapping is that the signal is very sensitive to inaccuracies in the flip angle value, thus potentially reducing the accuracy of T1 estimates. In practice, the nominal flip angle (i.e., the value set at the scanner) is different than the actual flip angle experienced by the spins (at 3T, variations of up to 30% are observed [15]), an issue that worsens with field strength. VFA typically requires the acquisition of another quantitative map, the transmit RF amplitude (B1+, or B1 for short), to calibrate the nominal flip angle to its actual value because of the B1 inhomogeneities that occur in most loaded MRI coils [16]. The need to acquire an additional B1 map reduces the time savings offered by VFA over saturation recovery techniques, and inaccuracies/imprecisions of the B1 map are also propagated into the VFA T1 map [15,17].
It has been widely reported in recent years that the accuracy of VFA T1 estimates is very sensitive to pulse sequence implementations [5,18,19], and as such is less robust than the gold-standard inversion recovery technique. In particular, the signal bias resulting from insufficient spoiling can result in inaccurate T1 estimates of up to 30% relative to inversion recovery estimated values [9]. VFA T1 map accuracy and precision are also strongly dependent on the quality of the measured B1 map [17], which can vary substantially between implementations [15]. Despite these drawbacks, VFA is still one of the most widely used T1 mapping methods in research. Its rapid acquisition time, short image processing time, and widespread availability makes it easy to use within other quantitative imaging acquisition protocols like quantitative magnetization transfer imaging and dynamic contrast-enhanced imaging.
NOTE: For in-depth coverage and more interactive content, please visit:
https://qmrlab.org/jekyll/2018/12/11/T1-mapping-variable-flip-angle.html
MP2RAGE
Dictionary-based T1 mapping techniques are increasing in popularity, due to their growing availability on clinical scanners, rapid scan times, and fast post-processing computation time, thus making quantitative T1 mapping accessible for clinical applications. Generally speaking, dictionary-based quantitative MRI techniques use numerical dictionaries—databases of pre-calculated signal values simulated for a wide range of tissue and protocol combinations—during the image reconstruction or post-processing stages.Popular examples of dictionary-based techniques that have been applied to T1 mapping are MR Fingerprinting (MRF) [20], certain flavors of compressed sensing (CS) [21,22], and Magnetization Prepared 2 Rapid Acquisition Gradient Echoes (MP2RAGE) [23]. Dictionary-based techniques can usually be classified into one of two categories: techniques that use information redundancy from parametric data to assist in accelerated imaging (e.g., CS, MRF), or those that use dictionaries to estimate quantitative maps using the MR images after reconstruction. Because MP2RAGE is a technique implemented primarily for T1 mapping, and it is becoming increasingly available as a standard pulse sequence on many MRI systems, the remainder of this section will focus solely on this technique.
However, many concepts discussed are shared by other dictionary-based techniques.
MP2RAGE is an extension of the conventional MPRAGE pulse sequence widely used in clinical studies [24,25]. A simplified version of the MP2RAGE pulse sequence is shown in Fig. 3. MP2RAGE can be seen as a hybrid between the inversion recovery and VFA pulse sequences: a 180inversion pulse is used to prepare the magnetization with T1 sensitivity at the beginning of each TRMP2RAGE, and then two images are acquired at different inversion times using gradient recalled echo (GRE) imaging blocks with low flip angles and short repetition times (TR). These two images at different TI times make it possible to generate quantitative T1 maps.
The widespread availability and turnkey acquisition/fitting procedures of MP2RAGE are main contributing factors to the growing interest for including quantitative T1 maps in clinical and neuroscience studies. T1 values measured using MP2RAGE show high levels of reproducibility for the brains of two subjects in an inter- and intra-site study at eight sites (same MRI hardware/software and at 7T) [26]. Not only does MP2RAGE have one of the fastest acquisition and post-processing times among quantitative T1 mapping techniques, it can also be used to acquire very high resolution T1 maps (1 mm isotropic at 3T and submillimeter at 7T, both under 10 min [27]), opening the doors to cortical studies which greatly benefit from the smaller voxel size [28–30].
Despite these benefits, MP2RAGE and similar dictionary-based techniques have certain limitations that are important to consider before deciding to incorporate them in a study. Good reproducibility of the quantitative T1 map is dependent on using one pre-calculated dictionary. If two different dictionaries are used (e.g., cross-site with different MRI vendors), the differences in the dictionary interpolations will likely result in minor differences in T1 estimates for the same data. Also, although the B1-sensitivity of the MP2RAGE T1 maps can be reduced with proper protocol optimization, it can be substantial enough that further correction using a measured B1 map should be done. Lastly, the MP2RAGE equations (and thus, dictionaries) assume monoexponential longitudinal relaxation, and this has been shown to result in suboptimal estimates of the long T1 component for a biexponential relaxation model [31], an effect that becomes more important at higher fields.
NOTE: For in-depth coverage and more interactive content, please visit:
https://qmrlab.org/2019/04/08/T1-mapping-mp2rage.html
T1rho mapping
T1 relaxation time at clinical fields (1.5 T or 3T) probes the molecular motional processes in the MHz range (e.g., 64 or 128 MHz). To measure such processes in the kHz range, while still performing the experiment at clinical fields, T1ρ relaxation can be used [32]. In a T1ρ relaxation experiment, a spin-lock RF pulse with amplitude B1 is applied in the rotating frame, parallel to the transverse magnetization [33]. The result is that the spins rotate around the spin-lock pulse in the rotating frame and will relax toward B1, similar to T1 relaxation (where the spins rotate around and relax toward B0). Owing to that similarity to the T1 relaxation experiment, T1ρ is known as the spin-lattice relaxation time in the rotating frame [33]. Figure 4 shows a simplified diagram of a T1ρ spin-lock pulse sequence.T1ρ can be used to probe small changes in the macromolecular content using clinically available equip- ment. The major challenge preventing T1ρ from being adopted clinically is that the power deposition required by spin-locking pulses approaches the clinical SAR limits. T1ρ dispersion, in particular, has limited clinical application because of power limitations from SAR concerns. There have been pulse sequence developments to overcome these challenges through the use of parallel transmit [34], partial k-space application of the spin-lock pulse [35], or the use of off-resonance pulses [36], though off-resonance T1ρ is beyond the scope of this discussion. However, there are benefits of even very low frequency (0 to 400Hz) spin-lock pulses, which are within clinical limits, to detect residual dipolar interactions in structured tissues such as oriented collagen fibers or myelinated axons [37].
NOTE: For in-depth coverage, please visit:
https://qmrlab.org/2019/04/09/T1-mapping-t1rho.html
Acknowledgements
These notes were written in collaboration with Kathryn Keenan and Mathieu Boudreau and were previously published under a creative commons license on the qMRLab blog (http://qmrlab.org/t1_book)
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