Francesca A. A. Leek1, Anna Therese Sjoholm1, Christiani Jeyakumar Henry2, Xiaodi Su3, Marlena C. Kruger4, and John J. Totman1
1A*STAR-NUS Clinical Imaging Research Centre, Singapore, Singapore, 2A*STAR Clinical Nutrition Research Centre, Singapore, Singapore, 3A*STAR Institute of Materials Research and Engineering, Singapore, Singapore, 4School of Food and Nutrition, College of Health, Massey University, Palmerston North, New Zealand
Synopsis
The
feasibility of utilising proximal femur cortical bone quality as a biomarker
for diabetes risk in post-menopausal
Chinese-Singaporean women was investigated. Non-dominant proximal femurs were
imaged with quantitative CT (QCT) and MR for the assessment of volumetric bone
mineral density (vBMD) and cortical bone porosity. A significant (p<0.01;
n=8) positive correlation between MRI vBMD and QCT vBMD for the region of
maximum cortical thickness was shown. Whether MRI vBMD is associated with
fracture risk and if it is sensitive to changes due to dietary or drug
intervention needs to be investigated to fully assess the clinical potential of
this method.Purpose
Bone
strength is characterised by bone mineral density (BMD) and bone quality. While
cohort studies have found an increased risk of bone fractures in patients with
type 2 diabetes, type 2 diabetics do not appear to have lower BMD than
non-diabetics.
1 The current gold standard for measuring areal BMD is
Dual-energy X-ray Absorptiometry (DXA); being a projection method, cortical and
trabecular bone are not differentiated nor is bone quality assessed. Three-dimensional
imaging methods are needed in order to determine whether volumetric BMD (vBMD)
or bone quality may be a potential biomarker for diabetes risk. The purpose of
this work is to assess the feasibility of utilising proximal femur cortical
bone quality obtained from quantitative imaging as a biomarker for diabetes
risk in post-menopausal Chinese-Singaporean (C-S) women.
Methods
100
post-menopausal C-S women will be recruited for this ongoing study. The
non-dominant proximal femur of each subject is assessed for vBMD with quantitative
CT (QCT, Siemens Biograph mCT) and T1 weighted in-phase gradient echo (T1-VIBE-DIXON)
MRI sequence (Siemens Prisma, 18-channel body array coil), and cortical bone porosity
with an MRI ultrashort echo-time (UTE) sequence; see Table 1 for imaging
parameters.
QCT
images are converted to dipotassium phosphate (K2HPO4)
equivalent densities using a commercial calibration phantom (Mindways QCT Pro) and
the region of maximum cortical thickness in the field of view, found distally
from the junction of the lesser trochanter and femoral shaft, are determined
from images segmented for cortical bone (threshold > 350 mg/cc). The total
effective dose is kept below 2 mSv for each subject.
MRI
vBMD is quantified using a T1-VIBE-DIXON MRI sequence with two external calibration
references (oil; 400 mg/cc calcium hydroxyapatite (CaHA) in H2O).
CaHA equivalent BMDs are estimated from the signal relationship and known
concentration of CaHA in the calibration references 2, for the
volume of interest (VOI) determined on QCT.
Bone
water concentration (BWC, shown to be a surrogate to cortical bone porosity 1)
is quantified using a coronal UTE sequence (10,000 radial spokes) and an
external reference (10% H2O in D2O doped with MAGNEVIST®).
The transverse relaxation time (T2*) is determined by fitting a
mono-exponential curve to images with TE<1.0 ms for all voxels within the
VOI determined on QCT. BWC is calculated using the method previously described 3;
J-modulation is included in the fitting model 4.
Results
For
the eight subjects analysed to date (age range 50-67 years; mean age 58.6 years),
the mean T2* of cortical bone was found to be 583 ± 22 µs and the mean BWC 16.9
± 3.6 % at the region of greatest cortical thickness. As would be expected, a
negative correlation between BWC calculated from MRI and vBMD from QCT is shown
in Table 2; this correlation is not significant (p>0.1).
The absolute
vBMDs for each imaging modality are not comparable as they are equivalent to
materials with different inherent densities. However, a significant (p<0.01) positive
correlation between vBMD derived from MRI and QCT for the region of maximum
cortical thickness is shown in Table 2.
Discussion
The
T2* of cortical bone was consistent with that found in literature, however, the
resultant BWC matched that expected for pre-menopausal women 2; the
correlation with QCT vBMD was not significant (p>0.1). Radiofrequency
inhomogeneity across the imaging volume and depth-dependent receive-coil
sensitivity could be causing signal variations between the external reference and
the deep-lying cortical bone resulting in the discrepancies seen. The use of an
internal reference standard to calibrate to an external reference of known composition should be investigated.
MRI
vBMD significantly positively correlates with QCT vBMD (p<0.01) in the
region of maximum cortical thickness in the proximal femur. This correlation
suggests that the previously reported signal model 2, used for
calculating MRI vBMD, is appropriate.
Conclusion
While
initial results indicate that MRI derived cortical bone vBMD has the potential
to be used in the assessment of bone quality, more extensive evaluation to
determine the method’s clinical potential in the early identification of diabetes
risk is needed. Other questions of particular clinical interest would be
whether MRI vBMD is associated with fracture risk, whether it is sensitive to
changes due to dietary or drug intervention and whether there is the potential
to use this low ionising radiation method for greater population screening.
Acknowledgements
This
project is part funded by Singapore-New Zealand Foods for Health Grant (BMRC grant
14/1/16/24/008).References
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et al. High-Resolution Peripheral Quantitative Computed Tomographic Imaging of
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