Mahesh H. Mankani, MD
Sergei A. Kuznetsov, PhD
Nilo A. Avila, MD
Albert Kingman, PhD
Pamela Gehron Robey, PhD
Index terms:
Animals
Bone marrow, transplantation
Bones, CT, 40.12119
Computed tomography (CT),
quantitative, 40.12119
Hydroxyapatite
Phantoms
Published online
10.1148/radiol.2302011529
Radiology 2004; 230:369 –376
Abbreviations:
BMD = bone mineral density
HA-TCP = hydroxyapatite–tricalcium
phosphate
ROC = receiver operating
characteristic
1
From the Division of Plastic Surgery,
Department of Surgery, University of
California–San Francisco, San Fran-
cisco General Hospital, 1001 Potrero
Ave, Ward 3A, San Francisco, CA
94110 (M.H.M.); Craniofacial and
Skeletal Diseases Branch (S.A.K.,
P.G.R.) and Biostatistics Core, Office of
the Director (A.K.), National Institute of
Dental and Craniofacial Research, Na-
tional Institutes of Health, Bethesda,
Md; Department of Radiology, Clinical
Center, National Institutes of Health, Be-
thesda, Md (N.A.A.). Received Septem-
ber 14, 2001; revision requested Oc-
tober 23; final revision received May
23, 2003; accepted June 18. Address
correspondence to M.H.M. (e-mail:
mmankani@sfghsurg.ucsf.edu).
Author contributions:
Guarantor of integrity of entire study,
M.H.M.; study concepts and design,
M.H.M.; literature research, M.H.M.;
clinical and experimental studies,
M.H.M., S.A.K.; data acquisition,
M.H.M., S.A.K., N.A.A.; data analysis/
interpretation, all authors; statistical
analysis, M.H.M., A.K.; manuscript
preparation, definition of intellectual
content, editing, revision/review, and
final version approval, all authors
©
RSNA, 2004
Bone Formation in
Transplants of Human Bone
Marrow Stromal Cells and
Hydroxyapatite–Tricalcium
Phosphate: Prediction with
Quantitative CT in Mice
1
PURPOSE: To determine whether quantitative computed tomography (CT) can be
used to estimate the extent of new bone formation in hydroxyapatite–tricalcium
phosphate (HA-TCP)– based transplants.
MATERIALS AND METHODS: Bone-forming transplants were generated by at-
taching cultured human bone marrow stromal cells to aliquots of HA-TCP particles
and were placed in subcutaneous pockets in immunocompromised mice. After 8
weeks, the transplants were individually imaged; each scan included a phantom.
Overall bone mineral density (BMD) of each transplant was obtained. Hematoxylin-
eosin–stained sections of the same transplants were then examined histologically,
which is the reference standard for assessing bone formation. The extent of bone in
each transplant was scored on a semiquantitative scale ranging from 0 to 4 by three
independent blinded observers; the bone score for each transplant was calculated
by averaging the three observer scores. BMD was compared with the histologically
determined bone score for each transplant. Statistical evaluations included (a)
calculation of empiric receiver operating characteristic curves to determine opti-
mum BMD thresholds and (b) determination of the relationship between BMD and
bone score, including derivation of Pearson correlation coefficients.
RESULTS: One hundred twenty transplants were evaluated. Average BMD of 600
mg/cm
3
K
2
HPO
4
or more was noted in transplants with appreciable bone formation
(bone score 3), while average BMD of less than 600 mg/cm
3
K
2
HPO
4
was seen in
transplants with poor bone formation (bone score 3) (P .001). Among trans-
plants with appreciable bone formation, the BMD was proportional to the extent of
mineralized matrix present in the new bone.
CONCLUSION: Use of quantitative CT offers a practical approach for the nonin-
vasive determination of new bone formation in mineralizing bone marrow stromal
cells and HA-TCP transplants.
©
RSNA, 2004
Transplantation of bone graft extenders, which can reduce the amount of bone graft
needed to complete a reconstruction, or bone graft replacements, such as osteoconductive
matrices, have gained considerable interest during the past few years. In lieu of or in
addition to bone autografts or allografts, surgeons have reconstructed bone defects with
materials that contain hydroxyapatite–tricalcium phosphate (HA-TCP) (1–12). However,
of great concern to reconstructive surgeons is the current lack of a reliable noninvasive
modality for the evaluation of new bone formation in the presence of these mineral-
containing matrices, since the extent of bone formation and therefore graft success is
uncertain (6,13–15). HA-TCP has a high density, comparable to that of cortical bone. On
369
R adiology