Development of Low-Field Nuclear Magnetic Resonance Technology to Determine Age-Related Human Bone Changes, 15-9187

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Principal Investigators
Qingwen Ni
J. Derwin. King

Inclusive Dates: 04/01/99 - Current

Background - Age-related bone fracture is a major health-care concern for the elderly. Such fractures may lead to high rates of mortality and morbidity. Although the underlying mechanisms are not well understood, previous studies have shown that increased bone porosity contributes significantly to the age-related decrease of bone mechanical strength. Small changes in porosity lead to significant changes in the stiffness and strength of compact and spongy bone. Changes in bone porosity are directly related to biomechanical bone properties. A direct-sensing technique to detect these changes in bone has been long required. Magnetic resonance imaging (MRI) techniques have been used as a noninvasive means to study soft tissue and the gross skeletal structure in situ, but MRI technology has insufficient resolution to image the fine pore structure in compact bone. Low-field NMR technology based on spin-spin (T2) measurements and analysis has been shown to have the capability to determine such porosity and pore size distribution in different porous media.

Approach - The objective of this project is to develop and verify a low-field, pulsed nuclear magnetic resonance (NMR) technique to determine the porosity and pore size distribution in human bone including compact bone. Investigations will be performed to explore age-related changes in the porosity and pore size distributions of human bone. The results obtained from NMR measurements will be compared with related clinic data of bone to verify the efficacy of the technique in detecting porosity and pore size distribution in bone. The project is composed of five tasks: 1) determine the porosity of bone in different age groups as well as in the same age group from the NMR measurement data; 2) obtain the inversion T2 relaxation spectra and intensity changes associated with the human bone from different age groups; 3) obtain the bone surface relaxivity constant and combine with T2 relaxation data to characterize the pore size distribution, and compare with the other test results; 4) determine the meaning of the spectral peaks associated with age-related intensity changes, that is, integrate porosity and pore size distribution and extract the organic phase and mineral phase information from the NMR data to develop a noninvasive and clinically valid methodology to quantify the porosity, density, and pore size distribution of bone in situ, particularly for compact bone; and 5) design and specify a volume-selective NMR measurement for in situ bone measurement applications.

Accomplishments - Twenty human cadaver compact bone samples ranging from 19 to 89 years old were collected and received from a bone laboratory. SwRI's existing 2.3- megahertz NMR proton apparatus was modified for the measurements. The total proton intensity for each sample was measured by the NMR free-induction decay (FID) method. The FID signal is caused by the liquid- and solid-phase protons inside the bone. These components include the water-like fluid present inside the pores (physical water), the bound water that has undergone hydration with the bone (chemical water), and the protons in the mineral matter. The liquid-like phase signal was measured by the CPMG spin-spin (T2) relaxation method. Thus, the total amplitude of T2 relaxation envelope is a representation of the amount of liquid phase inside the pores. The total volume (VB) of each bone sample was determined by Archimedes' principle. The NMR CPMG signal amplitudes were normalized to equivalent volumes of pore water by calibration with the NMR signal amplitude of a known volume of water (Vl). From these data, the porosity of the bone was calculated as Vl/VB. The results showed significant differences in porosity between the young group and the elderly group. Using a computer, the team then converted the obtained T2 relaxation data to inversion T2 relaxation spectra. The inversion T2 relaxation spectra can be transformed to the pore size distribution after the constant, surface relaxivity, is known. NMR proton T2 relaxation rate (1/T2) is proportional to the pore surface-to-volume ratio, with the longer T2 relaxation times corresponding to larger pores. Bone has a complex and highly hierarchical structural form at molecular, cellular, and microstructural levels. As a reasonable assumption, researchers can define the relaxation time distribution as a measure of an "effective" pore size distribution in bone. Selected aging samples have been sent to appropriate laboratories for composition tests by using Raman spectroscopy, and porosity and pore size evaluation by mercury porosimetry and histomorphometric tests. The resulting data will be compared with NMR results.

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