Tuning Nuclear Quadrupole Resonance: A Novel Approach for the Design of Frequency-Selective MRI Contrast Agents

Abstract

The interaction between water protons and suitable quadrupolar nuclei (QN) can lead to quadrupole relaxation enhancement (QRE) of proton spins, provided the resonance condition between both spin transitions is fulfilled. This effect could be utilized as a frequency selective mechanism in novel, responsive T 1 shortening contrast agents (CAs) for magnetic resonance imaging (MRI). In particular, the proposed contrast mechanism depends on the applied external flux density-a property that can be exploited by special field-cycling MRI scanners. For the design of efficient CA molecules, exhibiting narrow and pronounced peaks in the proton T 1 relaxation dispersion, the nuclear quadrupole resonance (NQR) properties, as well as the spin dynamics of the system QN-1 H, have to be well understood and characterized for the compounds in question. In particular, the energy-level structure of the QN is a central determinant for the static flux densities at which the contrast enhancement appears. The energy levels depend both on the QN and the electronic environment, i.e., the chemical bonding structure in the CA molecule. In this work, the NQR properties of a family of promising organometallic compounds containing 209 Bi as QN have been characterized. Important factors like temperature, chemical structure, and chemical environment have been considered by NQR spectroscopy and ab initio quantum chemistry calculations. The investigated Bi-aryl compounds turned out to fulfill several crucial requirements: NQR transition frequency range applicable to clinical 1.5-and 3 T MRI systems, low temperature dependency, low toxicity, and tunability in frequency by chemical modification.

Predicting quadrupole relaxation enhancement peaks in proton R1-NMRD profiles in solid Bi-aryl compounds from NQR parameters

“…The slight mismatch in frequency (down-shifted simulation) can be attributed to the temperature difference (simulation at 310 K, experiment at 295 K) and experimental errors both in the R 1 -NMRD profile and in the used NQR parameter for the simulation. As has been shown in [25], the temperature coefficient of NQR transitions around 310 K is expected about 10 kHz/K, at worst. For an assumed temperature difference of about 20 K, this means one can expect a shift of 0.2 MHz for the QRE peaks, which is of the order of the experimental resolution.…”

“…Equation (9) is evaluated for tris(2-6-dimethoxyphenyl) bismuthine and tris(2-methoxyphenyl) bismuthine based on their NQR parameters taken from [25]. The used input parameter Q cc , η, γ and the step sizes for B ev and ν Q for the calculations are summarised in Table 1.…”

“…The reason for this shape has been described elsewhere [26]. Input parameters for triphenylbismuth from reference [25]: Q cc = 668.87e6 MHz, η = 0.08, I = 9/2, γ Bi = 6.95 MHz/T, FWHM of signal intensity = 40 kHz. N = 200 (Colour online, B&W in print).…”

“…The filled solid line (blue) corresponds to the simulation using I − , the unfilled solid line (red) to the simulation using I − I − . An overlay of both procedures suggests a slightly better match in the Note: NQR parameter Q cc , η and linewidth γ = FWHM/2 at 310 K from reference [25]. a Low pass filter with coefficients equal to 1/span with span in percentage of number of data points.…”

“…This is especially favourable when considering the increasing interest in QN compounds creating QRE peaks in proton R 1 -NMRD profiles at high fields (e.g. 3 T) to use them as MRI contrast agents [25] while the measurements of such is not yet straightforward and connected with technical challenges. Also, the availability of such systems is not yet very high.…”