Parametric response mapping of CT images provides early detection of local bone loss in a rat model of osteoporosis.

Loss of bone mass due to disease, such as osteoporosis and metastatic cancer to the bone, is a leading cause of orthopedic complications and hospitalization. Onset of bone loss resulting from disease increases the risk of incurring fractures and subsequent pain, increasing medical expenses while reducing quality of life. Although current standard CT-based protocols provide adequate prognostic information for assessing bone loss, many of the techniques for evaluating CT scans rely on measures based on whole-bone summary statistics. This reduces the sensitivity at identifying local regions of bone resorption, as well as formation. In this study, we evaluate the effectiveness of a voxel-based image post-processing technique, called the Parametric Response Map (PRM), for identifying local changes in bone mass in weight-bearing bones on CT scans using an established animal model of osteoporosis. Serial CT scans were evaluated weekly using PRM subsequent to ovariectomy or sham surgeries over the period of one month. For comparison, bone volume fraction and mineral density measurements were acquired and found to significantly differ between groups starting 3 weeks post-surgery. High resolution ex vivo measurements acquired four weeks post-surgery validated the extent of bone loss in the surgical groups. In contrast to standard methodologies for assessing bone loss, PRM results were capable of identifying local decreases in bone mineral by week 2, which were found to be significant between groups. This study concludes that PRM is able to detect changes in bone mineral with higher sensitivity and spatial differentiation than conventional techniques for evaluating CT scans, which may aid in clinical decision making for patients suffering from bone loss.

[1]  T. Keaveny,et al.  Biomechanical computed tomography—noninvasive bone strength analysis using clinical computed tomography scans , 2010, Annals of the New York Academy of Sciences.

[2]  Bradford A Moffat,et al.  The functional diffusion map: an imaging biomarker for the early prediction of cancer treatment outcome. , 2006, Neoplasia.

[3]  R Bogaerts,et al.  Development of micro-CT protocols for in vivo follow-up of mouse bone architecture without major radiation side effects. , 2011, Bone.

[4]  S. Honig Osteoporosis - new treatments and updates. , 2010, Bulletin of the NYU hospital for joint diseases.

[5]  P. Geusens,et al.  Relationship Between Changes in BMD and Nonvertebral Fracture Incidence Associated With Risedronate: Reduction in Risk of Nonvertebral Fracture Is Not Related to Change in BMD , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[6]  Peter Boesiger,et al.  Bone metastases from prostate cancer: assessing treatment response by using diffusion-weighted imaging and functional diffusion maps--initial observations. , 2010, Radiology.

[7]  K. Imai Vertebral fracture risk and alendronate effects on osteoporosis assessed by a computed tomography-based nonlinear finite element method , 2011, Journal of Bone and Mineral Metabolism.

[8]  Timothy D Johnson,et al.  The parametric response map is an imaging biomarker for early cancer treatment outcome , 2009, Nature Medicine.

[9]  Todd E Peterson,et al.  Longitudinal live animal micro-CT allows for quantitative analysis of tumor-induced bone destruction. , 2011, Bone.

[10]  M. Olson,et al.  Ovariectomy, ovariohysterectomy and orchidectomy in rodents and rabbits. , 1986, The Canadian veterinary journal = La revue veterinaire canadienne.

[11]  R. Coleman Metastatic bone disease: clinical features, pathophysiology and treatment strategies. , 2001, Cancer treatment reviews.

[12]  R. Rizzoli,et al.  Sequential and precise in vivo measurement of bone mineral density in rats using dual‐energy x‐ray absorptiometry , 1992, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  Fran Harris,et al.  Improvement in spine bone density and reduction in risk of vertebral fractures during treatment with antiresorptive drugs. , 2002, The American journal of medicine.

[14]  Timothy D Johnson,et al.  Parametric response map as an imaging biomarker to distinguish progression from pseudoprogression in high-grade glioma. , 2010, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[15]  François Duboeuf,et al.  Rate of Forearm Bone Loss Is Associated With an Increased Risk of Fracture Independently of Bone Mass in Postmenopausal Women: The OFELY Study , 2005, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[16]  H Weinans,et al.  Detecting and tracking local changes in the tibiae of individual rats: a novel method to analyse longitudinal in vivo micro-CT data. , 2004, Bone.

[17]  Ursula Nemec,et al.  Imaging of insufficiency fractures. , 2011, Seminars in musculoskeletal radiology.

[18]  C. Hayes,et al.  Dual X-ray absorptiometry: recognizing image artifacts and pathology. , 2000, AJR. American journal of roentgenology.

[19]  Ralph Müller,et al.  In vivo micro-computed tomography allows direct three-dimensional quantification of both bone formation and bone resorption parameters using time-lapsed imaging. , 2011, Bone.

[20]  Charles R. Meyer,et al.  Demonstration of accuracy and clinical versatility of mutual information for automatic multimodality image fusion using affine and thin-plate spline warped geometric deformations , 1997, Medical Image Anal..

[21]  R. Huiskes,et al.  Effects of PTH treatment on tibial bone of ovariectomized rats assessed by in vivo micro-CT , 2009, Osteoporosis International.

[22]  Sharmila Majumdar,et al.  High-resolution imaging techniques for the assessment of osteoporosis. , 2010, Radiologic clinics of North America.

[23]  Bradford A Moffat,et al.  Functional diffusion map: a noninvasive MRI biomarker for early stratification of clinical brain tumor response. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[24]  R. Rubens,et al.  The clinical course of bone metastases from breast cancer. , 1987, British Journal of Cancer.

[25]  Timothy D Johnson,et al.  A feasibility study evaluating the functional diffusion map as a predictive imaging biomarker for detection of treatment response in a patient with metastatic prostate cancer to the bone. , 2007, Neoplasia.

[26]  H. K. Genant,et al.  Advanced CT bone imaging in osteoporosis , 2008, Rheumatology.

[27]  R. Turner,et al.  Differential effects of androgens on cortical bone histomorphometry in gonadectomized male and female rats , 1990, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[28]  A. Guenther,et al.  The backbone of progress--preclinical studies and innovations with zoledronic acid. , 2011, Critical reviews in oncology/hematology.

[29]  A. Tosteson,et al.  Incidence and Economic Burden of Osteoporosis‐Related Fractures in the United States, 2005–2025 , 2007, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[30]  R. Lorente-Ramos,et al.  Dual-energy x-ray absorptiometry in the diagnosis of osteoporosis: a practical guide. , 2011, AJR. American journal of roentgenology.

[31]  T. Wronski,et al.  Temporal relationship between bone loss and increased bone turnover in ovariectomized rats , 1988, Calcified Tissue International.

[32]  Bradford A Moffat,et al.  A feasibility study of parametric response map analysis of diffusion-weighted magnetic resonance imaging scans of head and neck cancer patients for providing early detection of therapeutic efficacy. , 2009, Translational oncology.

[33]  A. Hofman,et al.  Fracture incidence and association with bone mineral density in elderly men and women: the Rotterdam Study. , 2004, Bone.

[34]  Rik Huiskes,et al.  No effects of in vivo micro‐CT radiation on structural parameters and bone marrow cells in proximal tibia of wistar rats detected after eight weekly scans , 2007, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[35]  Klaus Engelke,et al.  Looking beyond bone mineral density , 2010, Annals of the New York Academy of Sciences.

[36]  Timothy D Johnson,et al.  Prospective Analysis of Parametric Response Map–Derived MRI Biomarkers: Identification of Early and Distinct Glioma Response Patterns Not Predicted by Standard Radiographic Assessment , 2011, Clinical Cancer Research.

[37]  H. Genant,et al.  Advanced imaging assessment of bone fragility in glucocorticoid-induced osteoporosis. , 2011, Bone.

[38]  G. Hortobagyi,et al.  Future directions of bone-targeted therapy for metastatic breast cancer , 2010, Nature Reviews Clinical Oncology.

[39]  W. Jee,et al.  Overview: animal models of osteopenia and osteoporosis. , 2001, Journal of musculoskeletal & neuronal interactions.

[40]  Timothy D Johnson,et al.  Functional diffusion map as an early imaging biomarker for high-grade glioma: correlation with conventional radiologic response and overall survival. , 2008, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[41]  Bradford A Moffat,et al.  An imaging biomarker of early treatment response in prostate cancer that has metastasized to the bone. , 2007, Cancer research.