A New Research Strategy for Evaluation and Assessment of Bone Quality, 15-R9618

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Principal Investigators
Qingwen Ni
Armando De Los Santos
Daniel Nicolella

Inclusive Dates:  04/01/06 – 10/01/07

Background - The fluid contained within bone tissue includes fluid explicitly within the intrinsic microstructural porosity (mobile phase), fluid contained within microcracks and diffuse damage, and fluid within the extracellular matrix (bound phase). It has been demonstrated that the fluid flow in bone plays a critical role in regulating bone adaptation. Understanding the role of water distribution within bone tissue to its mechanical behavior may provide further insight into the susceptibility of bone to fracture in the elderly population. It has been shown that age-related increases in bone porosity without significant changes in bone mineral density result in a decrease in bone strength. Bone fracture toughness is also significantly correlated to changes in porosity, microarchitecture, osteonal morphology, collagen integrity, microdamage, and water distribution, all of which are measures of bone quality. Unfortunately, current technology does not allow the nondestructive and noninvasive detection of bone water distribution or other measures of bone quality including microporosity. On the other hand, nuclear magnetic resonance (NMR) proton spin-spin (T2) or spin-lattice (T1) relaxation time measurements and analytical processing techniques have been used to determine microstructural characteristics of various types of fluid-filled porous materials. Currently the NMR relaxation technique has been applied to quantify the porosity, pore size distribution and microdamage in human cortical bone. Specifically, this project hypothesizes that cortical bone water distribution results in an alteration of the NMR spin-spin (T2) relaxation time signal caused by water in different phases (bound and mobile) in the bone matrix. This project further hypothesizes that the NMR spin-spin relaxation time (T2) spectrum derived parameters can be used as descriptions of bone quality (e.g. matrix ratio of bound water to mobile water, and porosity). 

Approach - The project objectives were: to quantify changes of proton NMR spin-spin (T2) relaxation signal in the bone bound and mobile water phases by using pulsed low field NMR measurements on machined samples of cortical bone taken from middle and elder age groups; to measure the effect of water distribution, porosity, and mineral density in machined samples of cortical bone on bone mechanical properties; to characterize physical bone porosity, mineral density and water distribution using standard methods and correlate these measurements of porosity and water distribution to the NMR spin-spin relaxation and material property measurements; and to address the feasibility of localized human cortical bone measurement by using an NMR single-sided-access and volume selected sensor approach. This proposed research will establish the range of application, accuracy and limitation of the technique.

Accomplishments - For female water distribution studies, cross-sections from the mid-diaphysis of 10 femurs were cut with a band saw. The samples taken at the indicated points on the bone and the determined size were for further three-point bending test. These bone samples were divided into two age groups. The middle-age group included ages 42, 49, 53, 54, and 58, while the old-age group were ages 72, 75, 78, 81, and 87. Final dimensions of the specimens were approximately 25 mm x 5 mm x 2 mm. For male water distribution studies, similar cross-sections and sample sizes were cut from 10 male donors and divided into two age groups. The middle-age group included bone obtained from donors age 51, 52, 55, 57, and 59. The old-age group included donors age 69, 76, 76, 77, and 87. In addition, a male femur (61 years old) was sectioned into three components: distal, middle, and proximal to extract specimens to investigate the distribution of water within specimens. The proximal section was further divided radially into nine blanks machined to final dimensions, resulting in nine specimens used for NMR measurements. The geometry of each specimen is a rectangular shape that is nominally 3 mm in width, 4 mm in height and 35 mm in length. All the specimens were stored in phosphate-buffered-saline-soaked gauze at -20 degrees C. Prior to NMR measurements, the samples were thawed at room temperature.

An SwRI-built 0.5 to 40 MHz broadline NMR system with an electromagnet 19 inches in diameter with a 4-inch gap was set up at a proton frequency of 27 MHz for these measurements. Spin-spin (T2) relaxation profiles were obtained using an NMR spin echo method. Each T2 profile, which included one thousand echoes (one scan with n = 1000), was acquired and sixth-four scans were used for the bone porosity measurements. The free induction decay (FID) signal was sampled and recorded at 2 microns per second intervals using a 9.5 microns per second wide 90 degree radio frequency pulse for the bone mobile water and bound water measurements. For each FID profile, 1,500 data points were acquired in one scan (an approximate 3 ms delay window). An inversion relaxation technique was used to invert the data to the T2 relaxation distribution spectrum.

This project determined the nondestructive and potentially in-vivo assessment of cortical bone mobile and bound water distribution and porosity, and correlated these measures of cortical quality to cortical bone strength. The findings of the present work suggest that NMR relaxation techniques are a potential tool for assessing bone quality in a nondestructive fashion. Currently, NMR has distinguished mobile water from bound water in such a way that each phase was associated with at least one mechanical property of cortical bone. Mobile water likely represents porosity, while bound water likely represents a combination of ultrastructural properties of bone tissue.

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