Synopsis
Millions of people worldwide suffer from bone
diseases, predisposing them to fractures and related comorbidities that have
devastating consequences. Imaging plays an important role in fracture risk assessment, diagnosis,
staging, and treatment monitoring of patients with bone diseases. Flexibility of MRI has paved the way for
non-invasive assessment of bone quality at multiple levels, including
trabecular and cortical bone. This talk will provide an overview of emerging MR-based
approaches for quantifying bone quality in human subjects.Clinical
Problem
Millions of people worldwide suffer from bone
diseases, predisposing them to fractures and related comorbidities that have
devastating consequences. Within a year of a hip fracture, 20-30% of patients will
die and 50% will lose the ability to walk [1-3].
Role
of Imaging
Imaging plays an important role in fracture
risk assessment, diagnosis, staging, and treatment monitoring of patients with
bone diseases. Radiographs and dual energy X-ray absorptiometry
(DXA), which provide semi-quantitative assessment, are the modalities of choice
for clinical management of metabolic bone diseases. Recent advances in
ultrasonography, nuclear medicine, computed tomography, and magnetic resonance
imaging (MRI) have enabled numerous non-invasive techniques for quantification
of bone quality. In particular, the flexibility of MRI has paved the way for
non-invasive assessment of bone quality at multiple levels, including
trabecular and cortical bone.
Assessment
of Trabecular Bone
Three
dimensional microstructure of trabecular bone in human subjects can be
visualized using high-resolution MRI [4, 5]. Early MRI studies of trabecular bone were limited to
skeletal extremities such as the distal radius, calcaneus, distal tibia,
proximal tibia, and distal femur. More recently, it has been shown that the proximal
femur - - the site of most traumatic fracture - - can be imaged at resolutions
sufficient to resolve individual trabeculae using spin-echo [6] and gradient-echo [7] techniques. High-resolution imaging of trabecular
bone has paved the way for elegant image analysis algorithms for extracting
information about various aspects of bone quality not previously feasible. For
example, it is now possible to characterize trabecular bone microarchitecture
using techniques such as digital topological analysis [8] and geodesic topological analysis [9].
Assessment
of Cortical Bone
The traditional thought has
been that decreased density and impaired structural integrity of trabecular
bone are primarily responsible for most osteoporotic fractures. However, 80% of
the weight of an adult human skeleton is cortical bone [10] and in the femoral neck, load is shared almost
equally between trabecular and cortical bone compartments [11]. Deterioration of intrinsic material properties, as
well as structural changes such as increased intracortical porosity, thinning
of the cortex, trabecularization of the endocortical regions, and periosteal
expansion contribute to reduced mechanical competence of cortical bone [12, 13]. Direct
imaging has been applied to assess cortical bone porosity [14], however, this type of technology can resolve only
the largest pores due to limitations in spatial resolution.
Assessment of Bone Water
Newer efforts have focused
on understanding factors other than bone mineral density that affect cortical
bone porosity, and as such it has recently been proposed that bone water be utilized
as a MRI biomarker of cortical bone quality [15]. Cortical bone has T2 relaxation times on the order
of only a few hundred microseconds and cannot be detected with conventional
imaging techniques where echo times are on the order of milliseconds. Ultrashort
echo time (UTE) MRI allows for echo times less than 100 microseconds, paving
the way for direct signal detection from short-T2 species such as cortical
bone. Several novel methods based on UTE MRI have been proposed and validated
for the assessment of cortical porosity in human subjects [16-18],
and new attempts have been made to achieve differential detection of signal
arising from various water pools within cortical bone, resulting from
recognition that water bound to collagen and water residing in pore spaces
correlate positively and negatively, respectively, with mechanical competence [19]. Horch et al developed a UTE-based sequence to obtain
signal from predominantly bound or pore water by incorporating T2 selective
single or double adiabatic inversion pulses, respectively [20]. Biswas et al proposed another UTE-based method to
separate bound and pore water signals via biexponential analysis of signal
decay by exploiting the differences in T2* relaxation times between the two
water components [21].
Assessment of Bone Matrix
and Mineral Properties
Phosphorus-31 (31P) is a major
component of bone mineral. Attempts are underway to characterize matrix and
mineral properties using solid state MRI, thereby potentially enabling the
differential diagnosis of osteoporosis from osteomalacia. Recent work has shown
that solid-state 31P MRI has the potential for quantification of bone mineral
density under in vivo conditions [22-24].
Acknowledgements
NIH R01 AR50068 and AR068382References
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