Salmon, Phil

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Micro-tomography bone imaging challenges: high resolution (Osteocyte lacunae), high density (metal implants) 

Phil Salmon

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Micro-tomography bone imaging challenges: high resolution (Osteocyte lacunae), high density (metal implants)

Positions and employment
1996e98 Assistant Professor, Departments of Pediatric
Dentistry and Medicine, UTHSCSA, San Antonio, TX
1998e06 Associate Professor (tenured, 2003), Oral Biology,
Dentistry, Univ. of Missouri-Kansas City, MO
2000e07 Director of Transgenic Core Facility, School of
Dentistry, Univ. of Missouri-Kansas City, MO
2006e07 Professor, Oral Biology, Dentistry, University of
Missouri-Kansas City, MO
2007 Professor with tenure, Biomedical Sciences, Texas
A&M Baylor College of Dentistry, Dallas, TX
2013 Vice Chair for research
198 AbstractsSelected Peer-reviewed Publications (Selected from over 140 peer-
reviewed publications)
1. Feng JQ., L.M. Ward, S. Liu, Y. Lu, B. Yuan, X. Yu, F. Rauch, Y. Xie, S.I.
Davis, S. Zhang, H. Rios, M.K. Drezner, L.F. Bonewald, L.D. Quarles and
K.E. White, (2006) Loss of DMP1 Causes Rickets and Osteomalacia and Iden-
tifies a Role for Osteocytes in Mineral Metabolism Nature Genetics
38:1310e5
2. B. Jiang, Z. Cao, Y. LU, C.B. Janik, S. Lauziere, Y. Xie, A. Poliard, C Qin,
LM. Ward, and Feng JQ. (2010) DMP1 C-terminal Mutant Mice Recapture the
Human ARHR Tooth Phenotype J Bone Mineral Res 25:2155e2164, PMID:
20499360
3. JQ. Feng, Feng-Jin Guo, Bai-Chuan Jiang, Sally Frenkel, Yan Zhang, David
Wang, Wei Tang, Y., Xie, Chuan-ju Liu, (2010) Granulin epithelin precursor: a
bone morphogenic protein 2-inducible growth factor that activates Erk1/2
signaling and JunB transcription factor in chondrogenesis Faseb Journal
24:1879e92, PMID: 20124436
4. Han XL, Liu M, Voisey A, Ren YS, Kurimoto P, Gao T, Tefera L, Dechow P, Ke
HZ, and Feng JQ. (2011)Postnatal Effect of Overexpressed DKK1 on Mandib-
ular Molar Formation. J Dent Res 90:1312e7, PMID: 21917600
5. Ma D, Zhang R, Sun Y, Rios HF, Haruyama N, Han X, Kulkarni AB, Qin C,
Feng JQ. (2011) A novel role of periostin in postnatal tooth formation and
mineralization. J Biol Chem 286:4302e9, PMCID: PMC3039381
6. Zhang R, Lu Y, Ye L, Yuan B, Yu S, Qin C, Xie Y, Drezner MK, Bonewald LF,
Feng JQ. (2011) Unique roles of phosphorus in endochondral bone forma-
tion and osteocyte maturation. J Bone Mineral Res 26:1047e56, PMID:
21542006
7. Yongbo Lu, Baozhi Yuan, Chunlin Qin, Yixia Xie, Sarah L. Dallas, Marc
D. McKee, Marc L. Drezner, Lynda F. Bonewald, and Feng JQ. (2011) The
Biological Function of DMP1 in Osteocyte Maturation is Mediated by its
57 kDa C-terminal Fragment J Bone Mineral Res 26: 331e340, PMID:
20734454
8. Z. Cao, H. Zhang, X. Zhou, X. Han, Y. Ren, T. Gao, Yin Xiao, B. de
Crombrugghe, M.J. Somerman, and Feng JQ. (2012) Genetic Evidence for
the Vital Function of Osterix in Cementogenesis J Bone Miner Res 27:1080-
92, PMID: 22246569
9. Feng JQ, Clinkenbeard EL, Yuan B, White KE, Drezner MK 2013 Osteocyte
regulation of phosphate homeostasis and bone mineralization underlies the
pathophysiology of the heritable disorders of rickets and osteomalacia. Bone
2013; 54(2):213-221
10. Shuxian Lin, Qi Zhang, Zhengguo Cao, Yongbo Lu, Hua Zhang, Kevin Yan,
Ying Liu, Marc D. McKee, Chunlin Qin, Zhi Chen, and JQ. Feng Constitutive
nuclear expression of dentin matrix protein 1 fails to rescue the Dmp1-null
phenotype J Biol Chem 2014 Jun 10. pii: jbc.M113.543330. [Epub ahead of
print]
MICRO-TOMOGRAPHY BONE IMAGING CHALLENGES: HIGH RESOLUTION
(OSTEOCYTE LACUNAE), HIGH DENSITY (METAL IMPLANTS)
Phil Salmon
Bruker-microCT, BelgiumBone and osteoporosis research has played a role in driving the development
of microCT systems with high resolution and throughput for analysis of
preclinical and clinical bone samples. Bone research continues to create
requirements that test the frontiers of performance of micro/nanoCT
technology. It does so in two different directions.
First, in the direction of submicron nano-CT imaging: interest is growing into
the role of osteocytes within the bone matrix. MicroCT can measure in 3D
the size, shape and distribution of osteocyte lacunae, providing information
about the history of lacunar formation and remodeling e a four dimensional
time-stamp of the activity of the osteoblasts-osteocytes in growing and
remodeling bone. Osteocyte lacunae have a diameter range of 5e9 microns,
meaning that microCT voxel sizes of near or below a micron are ideal for
accurate measurement of osteocyte lacunar morphology. Good image signal
to noise ratio is also essential to resolve the lacunae from noise dots.
Second, in the direction of imaging of metal orthopedic implants which pose
a particular difficulty for microCT due to strong Z4-proportional X-ray ab-
sorption and consequent extreme beam hardening in metals. It is not the im-
aging of metals per se that is the problem, but more the imaging of much
lower density materials surrounding the metal e and in this context bone it-
self becomes a “very low density material”. This is a different technical
challenge for microCT requiring innovations in camera and source technol-
ogy and reconstruction software.
A new nanoCT instrument, the SkyScan2211, represents a step toward
solving both the above requirements, with two X-ray cameras optimized
respectively for both the above imaging challenges. The first is an 11
megapixel CCD, precisely coupled without geometric distortion to a
scintillator optimized for submicron resolution. The second camera is a
flat panel detector with special radiation-hardened electronics, optimized
for large and high-density objects, and a thicker scintillator for detection of
high energy X-rays. An X-ray source is fitted which again meets both the
submicron and the large object-high density challenges. While allowing a
submicron emission spot size for submicron resolutions, it also has a high top
voltage of 190 kV, significantly extending the possibilities for imaging metal
objects such as orthopedic implants. This instrument thus provides a multi-
scale solution from submicron imaging up to imaging of large metal-
containing objects. It represents a new technical resource extending the
frontier of imaging possibilities for bone and orthopedic research.Fig. 1. Submicron pixel resolution allows visualisation and analysis of
osteocyte lacunae as well as mineralisation heterogeneity.
Abstracts 199Fig. 2. Imaging of bone close to a metal implant tests the ability of microCT
hardware and software to overcome artefacts associated with extreme
beam hardening in metals.
Brief CV
ResearchArea(s):Bonebiology,microCT imaging,quantitative 3D imageanal-
ysis, 3D visualisation software, tomographic reconstruction methods, in-vivo
small animal imaging, general microCT application support in many fields.
Technical Expertise: MicroCT imaging and 3D image analysis and quantifica-
tion (morphometry and microdensitometry), bone and dental biology; bone
histomorphometry (e.g. OsteoMeasure system) including dynamic fluores-
cent double-labelling, radiation biology and biophysics (alpha radionuclide
semiconductor detectors, solid state track detectors, nuclear contamination
monitoring, radionuclide dosimetry and biokinetics); marine biology,
oceanography.
Email: phil.salmon@bruker.com
Website: www.bruker-microct.com
CALCIUM-DEPENDENT ACTOMYOSIN CONTRACTILITY IN OSTEOCYTES
UNDER MECHANICAL LOADING
Edward Guo
Columbia University, USA
Intracellular Ca+2 ([Ca+2]i) oscillations, mediated by mechanosensitive Ca
+2
channels and the ER Ca+2 store, have been observed in osteocytes in
response to mechanical loading in vitro and ex vivo in our laboratory. While
many distant downstream gene expression pathways of [Ca+2]i signaling have
been studied, the immediate, temporally-regulated effects of these
numerous [Ca+2]i oscillations in osteocytes have not been elucidated. A
recent study in the gene expression of primary osteocytes has suggested
high levels of muscle contraction-related proteins. A hallmark of muscle is
its [Ca+2]i-dependent actomyosin contractility. We hypothesized thatosteocytes utilize [Ca+2]i oscillations to activate pulsing, muscle-like con-
tractile mechanical behavior. In this study, we used a quasi-3D imaging tech-
nique to simultaneously measure the contractile behavior of the actin
networks and [Ca+2]i in single osteocytes.
[Ca+2]i spikes were induced using fluid flow, ATP, or ionomycin in MLO-Y4 os-
teocytes. Contraction in the actin networks was measured immediately upon
onset of [Ca+2]i influx in all groups, indicated by a decrease in the strain
value. Microtubule networks did not display a similar contractile response.
Longer imaging of actin contractions displayed reversible, phasic contrac-
tions in the actin networks over a period of w180 s.
As non-muscle and smooth muscle myosin II isoforms are regulated by myosin
light chain kinase (MLCK) and skeletal and cardiac myosin II isoforms by
troponins, we sought to determine the myosin responsible for the observed
contraction. Under ATP stimulation, MLCK inhibition by ML-7 drastically
altered the kinetics of contraction, but skeletal and non-muscle myosin II
inhibition by blebbistatin had no effect. This pointed towards a smooth
muscle myosin mediated contraction. Furthermore, we verified the presence
of smooth muscle myosin heavy chain (SMMHC) in primary osteocytes and
MLO-Y4 osteocytes.
Here, we demonstrate a novel osteocyte mechano- and transduction
behavior where [Ca+2]i oscillations activate dynamic actomyosin contrac-
tions. Future studies will verify this mechanism in ex vivo osteocytes, as
well as investigate downstream behaviors of contractility in osteocytes,
such as contractility-mediated vesicle exocytosis.
Brief CV
Dr. Guo received his M.S. in 1990 and Ph.D. in 1994 in Medical Engineering
and Medical Physics from Harvard University-MIT. In 1994e1996, Professor
Guo did his postdoctoral fellowship in the Orthopaedic Research Labora-
tories at the University of Michigan at Ann Arbor with Professor Steven A.
Goldstein in orthopaedic bioengineering. In 1996 he joined the Department
of Mechanical Engineering and then Department of Biomedical Engineering
at Columbia University. He directs the Bone Bioengineering Laboratory in the
Department of Biomedical Engineering at Columbia focusing his research
interests in micromechanics of bone tissue, computational biomechanics,
and mechanobiology of bone. His past honors include Young Investigator
Recognition Award from the Orthopaedic Research Society, National
Research Service Award from the US National Institutes of Health (NIH), a
CAREER award from the US National Foundation of Science (NSF), Funds for
Talented Professionals (Joint Research Fund for Overseas Chinese Young
Scholars) from the National Natural Science Foundation of China. He was
elected as a fellow to the American Institute for Medical and Biological
Engineering. He was one of the founders and served as co-Editor-in-Chief of
Cellular and Molecular Bioengineering (CMBE), an international journal of US
Biomedical Engineering Society (BMES). He served as President of Interna-
tional Chinese Musculoskeletal Research Society, the Society for Physical
Regulation in Biology and Medicine, Member of Board of Directors of
Orthopaedic Research Society, and Member of Board of Directors of
American Institute for Medical and Biological Engineering.
Technical Expertise: Bone Mechanics, Imaging and Finite Element Analyses
of Human Bone Microstructure, Mchanobiology of Bone, Mechanotransduc-
tion, and Cell Mechanics.
Email: ed.guo@columbia.edu
TRACING STEM CELLS USING IN VIVO IMAGING TECHNIQUES IN BONE
REPAIR AND CANCER RESEARCH
Gang Li
Department of Orthopaedics and Traumatology, Faculty of Medicine,
The Chinese University Hong Kong, Hong Kong
Regenerative medicine with the use of stem cells is the therapeutic
alternative for many disease states. Questions remain regarding the viability


Micro-tomography bone imaging challenges: high resolution (Osteocyte lacunae), high density (metal implants)

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