NASA Human Research Program Investigators' Workshop (2012)
Quantitative Ultrasound Bone Diagnosis and Guided Therapy For Fracture Healing
Y-X. Qin1, J. Cheng1, L. Bi1, M. Pritz1, S. Ferreri1, C. Rubin1, W. Lin1
1
Department of Biomedical Engineering, SUNY Stony Brook, Stony Brook, NY 11794, USA
email: yi-xian.qin@sunysb.edu
4225.pdf
INTRODUCTION
Microgravity affects bone mineral density, microstructure and integrity, which lead to the risk of osteoporosis and fracture,
as well as nonunion. Advents in quantitative ultrasound (QUS) provide a unique method for evaluating both bone strength
and density, particularly under the extreme condition like long-term space mission. Moreover, ultrasound has been
demonstrated that can accelerate healing of fracture, as the mechanism of mechanobiology. The objective of this study has
two folds, 1) to evaluate the efficacy of a scanning confocal acoustic navigation (SCAN) QUS system for bone quality and
fracture assessment in localized interested region; and 2) to test a QUS guided ultrasound in acceleration of fracture healing
in a hindlimb suspension (HLS) model.
METHODS
Bone Quality Measurement: Based on the assessment of human trabecular bone SCAN device development, a refined QUS
imaging system was developed using an array scan mode [1,2]. QUS was processed to calculate the ultrasound attenuation
(ATT; dB), wave ultrasound velocity (UV), and the broadband ultrasound attenuation (BUA; dB/MHz). Both QUS
measurements was conducted in the region of interests covering an approximate 60x60 mm2 with 0.5 mm resolution.
Guided QUS for Fracture Healing: The experimental protocol is approved by Stony Brook University IACUC. Total of 36,
5-month old Sprague-Dawley rats were divided into six groups including 1) fracture control (FC, n=12), 2) fracture with
HLS (FS, n=12), and 3) fracture with HLS, plus QUS treatment (FSU, n=12). To simulate a microgravity condition,
standard fractures were performed at the middle of left femur of each animal, with HLS. K-Wire (Ti) was applied to the
rat’s femur from its knee condyle for stabilization [3]. Guided QUS was delivered transversally at the femur, 20 min/day, 5
days/wk for 5 weeks. Hindlimb bones were longitudinally imaged using µCT at 18 µm at week 1, 3 , and 5, and evaluated
for bone volume fraction (BVF) and bone volume (BV) in the callus. Mechanical testing was performed after sacrifice.
RESULTS
SCAN indicated sensitivity to identify fracture in the rat femur (Fig. 1) with resolution of 0.5mm. The SCAN image is able
to identify the region of interests even in the bone under 3mm in diameter of the cross section (Fig. 1). In the week 1 and 3,
there were no significant difference between control and HLS, and between QUS treated and untreated. However, in week
5, BVF in fracture with HLS (0.19±0.05) showed -6% lower than normal fracture (0.21±0.05), while QUS treated
(0.27±0.06) was 30% increase than the fracture control (p<0.05) (Fig. 2). In the 4-pt bending biomechanical testing, there
was no significant difference between normal fracture and fracture with HLS. However, the bone stiffness in QUS treated
fracture in HLS was 48% higher than untreated HLS fracture (p<0.05) (Fig. 3).
DISCUSSION
It has been demonstrated that the in vivo assessment of bone quality using SCAN predicts overall BMD distributions in the
region of interests, and capable to identify fracture. SCAN has shown its capability to sense subtle changes in bone in the
longitudinal BMD alteration. This can provide useful information for assessment of complications, such as non-union
fracture. With current techniques yielding only qualitative results, ultrasound could prove to be the keystone that allows us
to properly diagnose bone interdisposition. The disuse hind limb suspension indeed delayed the healing, e.g., in 5 weeks.
This delay is predicted to extend to the remodeling phase. Guided ultrasound treatment develops the best callus
mineralization quality, which is over 48% better than normal and HLS groups, indicating QUS can enhance healing under
disuse condition, and promote the bone mineralization. Guided ultrasound is also capable to mitigate bone loss and promote
healing in the identified region, which may provide early and targeted treatment for bone loss and fracture. Ultimately, it
may provide a portable, noninvasive device for bone loss assessment and treatment in space and on Earth. [Supported by
the NSBRI through NASA Cooperative Agreement NCC 9-58.]
REFEREMCES
[1] Qin, Y-X. et al, (2007) LNCS, ISSN:0302-9743 (p)/1611-3349 (online). 4901:216-233. [2] Qin Y-X. (2010) J Cosmology, 12, 37783780. [3] Bonnarens F, Einhorm TA. (1984) J Orthop 2, 97-101.
0. 35
Longitudinal Assessment of Bone Healing
450
400
FSU
SFC
FS
0. 25
FC
N
FC
0. 2
0. 15
0. 1
0. 05
350
300
250
200
150
100
50
0
0
1 week
Fig. 1. SCAN indentified rat femur fracture.
stiffness (N/mm)
BV/TV
FSU
0. 3
3 week
5 week
Fig. 2. Longitudinal bone mineralization.
nf c
sf c
f su
Fig. 3. Guided QUS improves bone stiffness.