Solid State MRI
One of the crucial parameters that is used to determine bone quality is the degree of bone mineralization which is conventionally defined as the mass of bone mineral per volume of bone matrix.
A closely related definition of the degree of mineralization is the ratio of bone mineral density (BMD) to bone matrix density. Knowledge of this parameter enables one to detect compositional changes in bone substance, and a key asset for distinguishing osteoporosis (low BMD but normal mineralization) from other metabolic bone diseases, such as osteomalacia (low BMD and low mineralization).
Currently, the degree of bone mineralization can only be measured by a bone biopsy. Working with our collaborators we are pioneering solid state MRI measurement of the degree of bone mineralization.
Our research has led to the
- .... development of a solid state magnetic resonance imaging (SMRI) technique to image the very short T2 signals of bone mineral and organic matrix, otherwise invisible by conventional MRI.
Our theory is that quantitative 31P SMRI will yield good representation in 3-dimensions of the mineral density in bone that has been supported by a series of in vitro and in vivo experiments (fig 1).
- ....development of a fat and water suppressed proton projection MRI (WASPI) which yields good mapping of organic matrix density in bone (fig 2).
Using this new technology, our group is conducting in vitro studies on bone mineralization of rats (fig 3). The Orthopedic NMR group is currently combining 31P SMRI and 1H WASPI to measure the degree of bone mineralization in live swine.
During early stages of bone mineralization there are many unknown features of chemical composition and crystal structure. Working with our collaborators we are using the following solid state NMR properties to study these unknown features.
- 1H - 31P cross polarization rate,
- chemical shifts, and
- spin-spin relaxation rate
The Orthopedic NMR Group
The Orthopedic NMR Group has accomplished the following:
- developed a cross-polarization technique to selectively suppress the signal of the dominant unprotonated phosphate resonance in bone mineral, while allowing the signal of the otherwise obscured protonated phosphate to be revealed.
confirmed that at an early stage in chick embryonic bone, the major component is phosphoprotein (phosphoryl groups), and identified a very minor element representing phosphoprotein complexed with Ca++ and a trace of Ca-P mineral phase in 8-day chick embryo bone.
This represents the first in situ data that phosphoproteins synthesized and deposited in the organic matrix of bone are later complexed with Ca++, and that this occurs coincidentally with onset of mineralization. Our next step is to identify these phosphoproteins.
- ...introduced a new chemical shift parameter ι, the magic angle sample spinning side band pattern index, and showed that i changes sign when organic phosphate associates with Ca++. This helps identify a small amount of organic phosphate associated with Ca++ in early stages of bone formation (fig 1).
- ...studied solid state 31P spin-spin relaxation to better understand the atomic and molecular properties of bone mineral; for example, that carbonate ions are more concentrated on crystal surfaces rather than inside the crystals.
- ...helped answer a decade-long controvery concerning the relationship between bone mineral and hydroxyapatite. Do bone mineral crystals contain hydroxyl ions?
We detected the existence of hydroxyl ions in bone mineral by a 2-dimensional solid state NMR spectroscopy technique, eliminating the need for specimen pretreatments used by other methods. A rough estimate yields a hydroxyl ion content of human cortical bone of about 20% of the amount expected in stoichiometric hydroxyapatite (fig 2).