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Quantitative magnetic resonance (QMR) method for bone and whole-body-composition analysis

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Abstract

Objective: to evaluate the applicability, precision, and accuracy of the new EchoMRI quantitative magnetic resonance (QMR) method for in-vitro bovine bone analysis and in-vivo whole-body-composition analysis of conscious live mice. Research methods and procedures: bovine tibia bone samples were measured by QMR and dual-energy X-ray adsorptiometry (DEXA). Repeated measures of whole-body composition were made using live and dead mice with different levels of fat by QMR and DEXA and by classic chemical analysis of the mouse carcass. Results: bone-mineral density (BMD) and bone-mineral content (BMC) measured in bovine tibia by QMR and DEXA were highly correlated. Precision of fat and lean measurement in mice was found to be better for QMR than for DEXA. The coefficient of variation (CV) for fat was 0.34–0.71% for QMR compared with 3.06–12.60% for DEXA. Discussion: QMR offers more specific parameters of bone structure than does DEXA. QMR and DEXA did not differ in the total amount of fat detected in live mice but QMR had improved precision. QMR was superior to DEXA in measuring fat in very small mice. Conclusions: in bone tissue there is a strong correlation between hydrogen NMR signal and bone-mineral density as measured by X-ray. QMR provides a very precise, accurate, fast, and easy to use method for determining fat and lean mass of mice without the need for anesthesia. Its ability to detect differences and monitor changes in body composition in mice with great precision should be of great value in characterizing phenotypes and studying drugs affecting obesity.

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Authors and Affiliations

  1. Echo Medical Systems, 11191 Westheimer, #223, Houston, TX 77042, USA

    Gersh Z. Taicher & Arcady Reiderman

  2. Eli Lilly Research, Indianapolis, IN 46285, USA

    Frank C. Tinsley & Mark L. Heiman

Authors
  1. Gersh Z. Taicher
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  2. Frank C. Tinsley
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  3. Arcady Reiderman
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  4. Mark L. Heiman
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Corresponding author

Correspondence to Gersh Z. Taicher.

Appendix: basics of nuclear magnetic resonance

Appendix: basics of nuclear magnetic resonance

When hydrogen nuclei are placed in an applied static magnetic field, a small majority of spins are aligned with the applied field in the lower energy state, since it is more stable than the higher energy state. The individual spins precess about the applied static magnetic field at a resonance frequency, also termed the Larmor frequency. This frequency is characteristic of a particular nucleus and proportional to the applied static magnetic field. An alternating magnetic field at the resonance frequency in the radio frequency (RF) range, applied by a transmitting antenna to a subject or specimen in the static magnetic field, flips nuclear spins from the lower energy state to the higher energy state. When the alternating field is turned off, the nuclei return to the equilibrium state with emission of energy at the same frequency as that of the stimulating alternating magnetic field. This RF energy generates an oscillating voltage in a receiver antenna, whose amplitude and electronic rate of decay depend on the physicochemical properties of tissue and the magnetic environment of the nuclei. The applied RF field is designed to perturb the thermal equilibrium of magnetized nuclear spins, and the time dependence of emitted energy is determined by the manner in which this system of spins returns to equilibrium magnetization. The return is characterized by two parameters: T 1, the longitudinal or spin–lattice relaxation time; and T 2, the transverse or spin–spin relaxation time.

Whereas conventional X-ray radiographic and computed tomography images depend on electron density, NMR/MRI depends on the density of hydrogen nuclei and the physical state of the tissue as reflected in the T 1 and T 2 relaxation times. In general, NMR/MRI instruments create contrast between soft tissues by taking advantage of the differences in relaxation times of the hydrogen spins and (or) hydrogen density in these tissues. NMR signals also depend on diffusion properties and the temperature of the material that is being investigated.

Various sequences (selectable length and duration) of RF magnetic fields are imparted to the tissue to momentarily re-orient nuclear magnetic spins of hydrogen nuclei. RF signals are generated by hydrogen nuclei as they spin about their axes due to precession of the spin axes. The amplitude, duration, and spatial distribution of these RF signals are related to properties of the material, which are investigated by the NMR technique used. Tissue contrast is high between fat, body free fluid, and muscle based on NMR signal amplitude and relaxation time, and can be further enhanced by application of certain RF sequences.

High-resolution NMR techniques or MRS methods depend on different proton resonance frequencies for protons in chemically different environments [64]. The magnetic field strength experienced by these protons is usually less than that of the applied static magnetic field due to diamagnetic shielding caused by the motion of their valence electrons and those of adjacent atoms in response to the applied magnetic field. These differences are called chemical shifts and are usually measured with respect to some reference standard. Water can be easily distinguished from oils and fats based on NMR high-resolution spectra. Low-resolution NMR spectra will exhibit one single "wide line" at the weighted mean proton resonance frequency for a mixture of water and oil. This technique is referred to in the literature as "wide-line" NMR [65]. The technique measures the voltage induced in a receiving antenna, which is proportional to the total number of hydrogen nuclei.

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Taicher, G.Z., Tinsley, F.C., Reiderman, A. et al. Quantitative magnetic resonance (QMR) method for bone and whole-body-composition analysis. Anal Bioanal Chem 377, 990–1002 (2003). https://doi.org/10.1007/s00216-003-2224-3

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