Development of Low-Field Nuclear Magnetic Resonance
Inclusive Dates: 04/01/99 - 10/01/01
Background - Age-related fracture of bone is a major concern of health care for the elderly population because such fractures may lead to high rates of mortality and morbidity. Although the underlying mechanisms are not well understood, previous studies have shown that increases in the porosity of bone considerably contribute to the age-related decrease of bone mechanical strength. It is known that small changes in porosity would lead to significant changes in the stiffness and strength of both compact and spongy bone. Because changes in bone porosity are directly related to biomechanical properties of bone, a direct-sensing technique to detect such changes in bone has been long wanted. 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 does not have sufficient resolution to image the fine pore structure in compact bone. Low field nuclear magnetic resonance (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 NMR technique to determine the porosity and pore size distribution in human bone, including compact 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, 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 use in in situ bone measurement applications.
Accomplishment - Twenty human cadaver compact bone samples ranging from 19 to 89 years old were collected and received from related bone laboratory. The 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 due to the liquid- and solid-phase protons inside the bone, which includes 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 volumes (VB) of each bone sample were 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 a significant difference in porosity between the young group and the elderly group. All the obtained T2 relaxation data were computerized to inversion T2 relaxation spectra. It is known that 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 known to be proportional to the pore surface-to-volume ratio, with the longer T2 relaxation times corresponding to larger pores. The team proposed and used the method in which mercury porosimetric results provided the median pore size diameter and the T2 inversion relaxation spectrum provided the median T2 relaxation time constant. By using the relationship between the pore median pore size and median T2 relaxation time, the relaxivity was estimated. Because bone has a complex and highly hierarchical structural form at molecular, cellular, and microstructural levels, further verifications are needed. The results obtained from NMR measurements have compared and correlated with the results from currently available but destructive methods such as histomophormetric and mercury porosimetric measurements to verify the porosity and pore size distributions and the feasibility of this methodology.