T1ρ, T2ρ: Definition & Quantification
Shalom Michaeli1
1University of Minnesota, United States

Synopsis

Keywords: Contrast mechanisms: Rotating Frame Relaxometry, Contrast mechanisms: Microstructure, Image acquisition: Quantification

Rotating frame relaxation methods based on FS pulses, including T1ρ and T2ρ using adiabatic pulses, and the non-adiabatic method entitled Relaxation Along a Fictitious Field (RAFF) in the rotating frame of rank n (RAFFn), offer sensitivity to a broad range of motional regimes. The reduced power deposition of RAFFn, along with the opportunity of enhancing sensitivity to exchange by tuning the periodicity of irradiation, are distinct advantages of the methodology. The methodologies for detection of fast relaxing spins using asymptotic relaxation mapping and alternating Look-Locker sequence are described. Applications of T1ρ, T2ρ and RAFFn for detecting pathological conditions are presented.

TARGET AUDIENCE

Researchers who seek to advance currently available MRI and MRS modalities for multiple applications including research and clinical platforms, with the ultimate goal of characterizing microstructural tissue properties and pathophsyiological processes in vivo.

OUTCOME/OBJECTIVES

Participants will be informed on how to generate MRI contrast and to probe molecular dynamic processes of interest by using rotating frame methodologies, in particular based on amplitude and frequency modulated pulses.

PURPOSE

Among the large variety of motional regimes that water molecules experience in tissue, those in intermediate-slow regimes are the most sensitive to the intricate nature of tissue microstructure, composition and function [1, 2]. To tune MRI exam to a specific regime of molecular motion, including intermediate and slow, relaxation in multiple rotating frames of rank “n” can be exploited. The correlation times of motion involved in this case are in the range of τc~(γB(n)eff)-1 , where B(n)eff is an effective magnetic field in the rotating frame of rank (n-1) [3-8]. T1ρ relaxation can assess motional regimes with correlation times τc~1/ωeff in micro to millisecond time scale, with conventionally used spin-locking [9-13], as well as with adiabatic RF pulses [1, 2, 14, 15]. An interest towards in vivo exploitation of T1ρ and T2ρ MRI is highly motivated by the utility of these methodologies in applications to multiple diseases, including Parkinson’s disease[16], Multiple Sclerosis[17, 18], essential tremor[19], epilepsy[20], MSK [21] and many others. For example, in rat models of cerebral ischemia, T1ρ relaxation is one of the earliest markers that reflect irreversible tissue damage after cessation of blood flow [22] even in those cases where initial diffusion abnormality may transiently recover upon reperfusion [23, 24]. RAFFn had been demonstrated to be sensitive to demyelination and remyelination process in vivo[25]. However, high SAR severely limits the use of some of these approaches in clinical settings, thus warranting the exploration of novel methods.

METHODS

To access slow and ultra-slow motions (millisecond time scale) with lower SAR, one can measure relaxations in higher rotating frames with the rank n ≥ 2. Our group has introduced adiabatic T1ρ and T2ρ techniques, and nonadiabatic RAFFn which operates in high rotating frames. In adiabatic T1ρ and T2ρ techniques train of adiabatic full passage pulses is placed prior or after the excitation pulse, respectively. With RAFFn the adiabatic condition is purposely violated and spin Hamiltonian is transformed to high rotating frames. We demonstrate that the periodic irradiation during RAFFn can be utilized to probe exchange, and we developed new method to detect fast relaxing spins using zero echo time imaging readout MB-SWIFT.

RESULTS

The benefits of high rotating frame technique RAFFn in reducing SAR have been demonstrated in earlier work [26]. For instance, a substantial reduction in SAR can be appreciated when comparing RAFF5 with spin-lock T1ρ of similar peak RF amplitude. Another compelling feature of RAFFn involves an enhanced sensitivity to spin coupled systems resulting from the periodic nature of the RF irradiation. The periodic Hamiltonian indeed probes the exchanging spin system, leading to a significant increase of the observed relaxation rate due to the instantaneous flip of the effective field and the generation of sidebands. With RAFFn, the periodicity of RF irradiation can easily be tuned to generate sidebands. By tuning the irradiation period to chemical shift differences between exchanging sites, a significant increase in the exchange-induced relaxation rate constants can be achieved. Using 3D zero echo time MB-SWIFT technique, we developed method for detection of T1ρ and free precession T1 based on alternating Look – Locker sequence.

DISCUSSION

Unique and complementary insights into molecular processes linked to tissue function can be gained by characterizing the dynamic properties of protons. The SNR increase of high magnetic fields offers an undeniable advantage which however needs to be leveraged with the challenge of maintaining the flexibility of tuning the MRI contrast to the molecular dynamics of interest. Rotating frame relaxations measured during the application of frequency-modulated pulses offer sensitivity to intermediate and slow regime of molecular dynamics. They offer also practical advantages as compared to continuous-wave rotating frame relaxations, including a minimized sensitivity to B1 distributions and a capability to simultaneously tune the contrast to multiple effective fields, Beff(t) [27]. MRI relaxation methods based on frequency swept RF pulses, including adiabatic T1ρ and T2ρ using adiabatic full passage pulses, and the non-adiabatic method RAFF in the rotating frame of rank n (RAFFn) [1, 2, 14, 26-29] provide insights into the pathological processes of multiple brain disorders, such as Parkinson’s disease and essential tremor [16, 19, 30], aging research [31], CNS neoplasm [32], stroke [33], MS [34, 35], and cell death in rat glioma gene therapy model [36]. They also hold promise for elucidating pathophysiologic processes that histologic studies suggest are important in MS [17, 18]. Although not common yet for clinical studies, rotating frame relaxations with FS pulses were proven as robust and sensitive methods for a variety of in vivo investigations conducted by our group [16, 17, 30, 33, 36-40] and others [41, 42].

CONCLUSION

The clinical relevance of rotating frame relaxation contrasts (i.e. T1ρ, T2ρ and RAFFn with and without periodic irradiation enhancement) motivates their continued development especially at high fields. The reduced power deposition of the RAFF acquisitions, along with their flexibility in enhancing sensitivity to exchange by tuning the periodicity of irradiation, are distinct advantages of the methodology as compared to other relaxation or CEST methods.

Acknowledgements

NIH core grant P41 EB027061 ; R01MH127548; R01 NS129739

References

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