Molecular basis of water proton relaxation in gels and tissue

Abstract

An extensive set of water-1 H magnetic relaxation dispersion (MRD) data are presented for aqueous agarose and gelatin gels. It is demonstrated that the EMOR model, which was developed in a companion paper to this study (see Halle, this issue), accounts for the dependence of the water-1 H spin-lattice relaxation rate on resonance frequency over more than four decades and on pH. The parameter values deduced from analysis of the 1 H MRD data are consistent with values derived from 2 H MRD profiles from the same gels and with small-molecule reference data. This agreement indicates that the water-1 H relaxation dispersion in aqueous biopolymer gels is produced directly by exchange-mediated orientational randomization of internal water molecules or labile biopolymer protons, with little or no role played by collective biopolymer vibrations or coherent spin diffusion. This ubiquitous mechanism is proposed to be the principal source of water-1 H spin-lattice relaxation at low magnetic fields in all aqueous systems with rotationally immobile biopolymers, including biological tissue. The same mechanism also contributes to transverse and rotating-frame relaxation and magnetization transfer at high fields. Intrinsic contrast in magnetic resonance images of soft tissue is generated largely by spatial variations in spin relaxation rates. Whereas the phenomenology of water-1 H relaxation in tissue is well documented (1-3), the underlying molecular mechanism remains controversial (4 -9). The task of elucidating the relaxation mechanism is complicated by incomplete knowledge about the chemical composition and supramolecular structure of most tissues. In addition, it is usually not possible to vary biopolymer composition, pH, or temperature in a controlled way while maintaining the integrity of the tissue. For these reasons, most mechanistic studies have been carried out on model systems, such as aqueous biopolymer gels, with relaxation characteristics similar to those of tissue. Here we report an extensive set of water-1 H relaxation data from two widely used tissue models: aqueous gels of agarose and gelatin.Detailed information about relaxation mechanisms in complex systems can be obtained from the magnetic relaxation dispersion (MRD) profile, that is, the field/frequency dependence of the spin-lattice relaxation rate, R 1 ϭ 1/T 1 . Ideally, the dispersion profile should be recorded from typical MRI frequencies of order 100 MHz down to the kHz range. The water-1 H MRD profiles reported here cover more than four frequency decades. The strong frequency dependence of R 1 at low fields, which is the focus of the present study, can be used to enhance image contrast in prepolarized MRI experiments (10). The low-field R 1 dispersion also yields information about the zero-frequency dipolar contributions to transverse relaxation and steadystate magnetization transfer and to the low-frequency dipolar contribution to rotating-frame spin-lattice relaxation.Agarose is a linear polysaccharide with a disaccharide repeat (agarobiose) composed...

Nuclear magnetic relaxation induced by exchange-mediated orientational randomization: Longitudinal relaxation dispersion for a dipole-coupled spin-1/2 pair

“…28,34 Corresponding water 1 H MRD studies are less useful for extracting clear-cut biophysical information, since the smaller coupling constant (ω D is an order of magnitude smaller than ω Q ) allows more labile protons to contribute to R 1 in addition to well-defined internal hydration sites. Nevertheless, 1 H MRD can sometimes be a useful complement to water 2 H MRD measurements 20 and, in addition, can be used to study cosolvent interactions with proteins or other macromolecules.…”

“…We also consider various limiting cases of the general theory and we delineate the quantitative breakdown of the previously used nonrigorous extension of the Solomon equations. [18][19][20] In Sec. V, we calculate the MRD for like (homonuclear) spin pairs, e.g., two protons, along the same lines as in Sec.…”

“…In the past, such data have been interpreted [15][16][17] with semi-phenomenological models involving dubious assumptions about the relaxation-inducing motions. 18,19 Previous water 1 H MRD studies of biopolymer gels from this laboratory 19,20 made use of a nonrigorous extension of the multi-spin Solomon equations to conditions outside the motional-narrowing regime. For a two-spin system, this approach 18 is closely related to a well-known result 21 for twophase relaxation in the dilute regime.…”

SQUID magnetometry from nanometer to centimeter length scales

“…The enhanced contrast is due to interactions of protons in water with those bound to large, non-rotating biomolecules, and is enhanced at low …eld strengths. This was recently demonstrated both theoretically and experimentally in studies of agarose gels [38,39]. Although there is not a quantitative model for such relaxation mechanisms in human tissue, it is expected that this relaxation mechanism, which is not accessed in conventional MR imaging, will provide opportunities to distinguish tissues which currently do not currently have a successful imaging method.…”

Nuclear magnetic relaxation by the dipolar EMOR mechanism: General theory with applications to two-spin systems

“…Previously, such data have been interpreted with semi-phenomenological models [1][2][3] involving questionable assumptions about the relaxation-inducing motions. 4,5 Earlier water 1 H MRD studies of biopolymer gels from this laboratory 5,6 made use of a nonrigorous extension of the multi-spin Solomon equations to conditions outside the motional-narrowing regime.…”