A new method to measure rotating frame relaxation and to create contrast for MRI is introduced. The technique exploits relaxation along a fictitious field (RAFF) generated by amplitude- and frequency-modulated irradiation in a sub-adiabatic condition. Here, RAFF is demonstrated using a radiofrequency pulse based on sine and cosine amplitude and frequency modulations of equal amplitudes, which gives rise to a stationary fictitious magnetic field in a doubly rotating frame. According to dipolar relaxation theory, the RAFF relaxation time constant (TRAFF) was found to differ from laboratory frame relaxation times (T1 and T2) and rotating frame relaxation times (T1ρ and T2ρ). This prediction was supported by experimental results obtained from human brain in vivo and three different solutions. Results from relaxation mapping in human brain demonstrated the ability to create MRI contrast based on RAFF. The value of TRAFF was found to be insensitive to the initial orientation of the magnetization vector. Finally, as compared with adiabatic pulse trains of equal durations, RAFF required less radiofrequency power and therefore can be more readily used for rotating frame relaxation studies in humans.

Spin relaxation taking place during radiofrequency (RF) irradiation can be assessed by measuring the longitudinal and transverse rotating frame relaxation rate constants (R 1ρ and R 2ρ ). These relaxation parameters can be altered by utilizing different settings of the RF irradiation, thus providing a useful tool to generate contrast in MRI. In this work we investigate the dependencies of R 1ρ and R 2ρ due to dipolar interactions and anisochronous exchange (i.e., exchange between spins with different chemical shift δω≠0) on the properties of conventional spin-lock and adiabatic pulses, with particular emphasis on the latter ones which were not fully described previously. The results of simulations based on relaxation theory provide a foundation for formulating practical considerations for in vivo applications of rotating frame relaxation methods. Rotating frame relaxation measurements obtained from phantoms and from the human brain at 4T are presented to confirm the theoretical predictions. Keywordsrotating frame relaxations; spin-lock; adiabatic pulses; dipolar interactions; anisochronous exchange; MR contrast A. IntroductionRotating frame relaxation rate constants, R 1ρ and R 2ρ , characterize relaxation during radiofrequency (RF) irradiation when the magnetization vector is aligned with or perpendicular to the direction of the effective magnetic field ( ), respectively. R 1ρ and R 2ρ reflect the features of the spin dynamic processes, and depend on the properties of the RF irradiation [1][2][3][4]. The latter feature creates the possibility to "manipulate" the measured R 1ρ and R 2ρ by choosing different settings of the RF irradiation, thus leading to the generation of MR contrast [5,6]. Whereas the spin-lattice relaxation rate constant R 1 is sensitive to dynamic processes close to the Larmor frequency (ω 0 /(2π)), which is in the order of MHz for standard in vivo applications, in the majority of cases the rotating frame relaxations are additionally Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. sensitive to fluctuations close to the effective frequency (ω eff /(2π), where ω eff = γB eff and γ is the gyromagnetic ratio), which is in the order of kHz. The enhanced sensitivity of R 1ρ and R 2ρ to molecular dynamics in the kHz range makes rotating frame relaxations a practical tool for gaining information about water spin dynamics and interactions with endogenous macromolecules [7]. Application of these methods holds great potential for addressing several biological questions, especially at high magnetic fields. NIH Public AccessA typical method to measure R 1ρ ...

Background— For clinically relevant proangiogenic therapy, it would be essential that the growth of the whole vascular tree is promoted. Vascular endothelial growth factor (VEGF) is well known to induce angiogenesis, but its capability to promote growth of larger vessels is controversial. We hypothesized that blood flow remodels vascular growth during VEGF gene therapy and may contribute to the growth of large vessels. Methods and Results— Adenoviral (Ad) VEGF or LacZ control gene transfer was performed in rabbit hindlimb semimembranous muscles with or without ligation of the profound femoral artery (PFA). Contrast-enhanced ultrasound and dynamic susceptibility contrast MRI demonstrated dramatic 23- to 27-fold increases in perfusion index and a strong decrease in peripheral resistance 6 days after AdVEGF gene transfer in normal muscles. Enlargement by 20-fold, increased pericyte coverage, and decreased alkaline phosphatase and dipeptidyl peptidase IV activities suggested the transformation of capillaries toward an arterial phenotype. Increase in muscle perfusion was attenuated, and blood vessel growth was more variable, showing more sprouting angiogenesis and formation of blood lacunae after AdVEGF gene transfer in muscles with ligated PFA than in normal muscles. Three-dimensional ultrasound reconstructions and histology showed that the whole vascular tree, including large arteries and veins, was enlarged manifold by AdVEGF. Blood flow was normalized and enlarged collaterals persisted in operated limbs 14 days after AdVEGF treatment. Conclusions— This study shows that (1) blood flow modulates vessel growth during VEGF gene therapy and (2) VEGF overexpression promotes growth of arteries and veins and induces capillary arterialization leading to supraphysiological blood flow in target muscles.