Validation of in vivo cancellous bone assessment using high resolution imaging and histologic examination

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1 Validation of in vivo cancellous bone assessment using high resolution imaging and histologic examination Luke Arentsen, PhD Medical Physics Resident University of Minnesota

2 Cancellous bone has a higher rate of bone remodeling Cancellous bone mineral density (BMD) would be a better metric of acute skeletal change than cortical BMD Cancellous bone is less dense than cortical bone Small changes in marrow composition cause significant changes in cancellous BMD Introduction

3 Rational Cancer survivors experience a greater risk of fracture compared to the general population [Baxter, 2005] However, the effect of cancer treatment, especially the relationship between marrow fat (MF) and BMD, are not well known Changes in marrow composition can affect estimation of BMD and may confound true changes in cancellous BMD if the two types of marrow are not distinguished

4 Methods: Imaging & Histology 5 human cadavers were imaged with DECT and MRI within 24 hrs of death 21 vertebral bodies excised, imaged with µct, and processed for H&E histology

5 Merge Histological data with Imaging

6 Results: Bone Marrow Yellow marrow fraction intensity Marrow fat estimate: Histology and in vivo imaging DECT (YMF) wfmri Histologic ratio of marrow fat (AV/TV) The AV/TV of 21 lumbar vertebrae ranged from 0.18 to 0.75 with a mean (SD) of 0.36 (0.18) There were moderate correlations between the AV/TV and the results of DECT and wfmri (r = 0.80 and 0.77, respectively)

7 Results: Bone mineral

8 Cadaver study - Discussion The increase of marrow fat (or adipogenesis) provides a biological process by which bone loss occurs; If mesenchymal stem cells commit to marrow fat then osteoblastogenesis decreases Since CT scans are regularly given as part of the diagnosis, treatment and followup process, DECT could become very useful to the study of cancer survivors bone health Correcting for marrow composition can provide a more accurate estimate of the osseous density within a bone

9 Conclusion Marrow fat fraction intensities were validated with histologic quantification of adipocyte prevalence We established the feasibility of DECT to measure the impact of cancer treatment on MF and BMD MF and mcbmd should be considered independently when monitoring the adverse effects of cancer therapy The ability to correct for marrow composition makes DECT imaging of the entire human body able to accurately assess cancellous BMD heterogeneity

10 Acknowledgements University of Minnesota UofMN Medical Center Fairview Center for Magnetic Resonance Research UofMN Anatomy Bequest Program The women who donated their time and bodies for the advancement of education and research University Imaging Centers Mindways Software Inc. Dr. Keenan Brown Twin Cities histology Bionet Histological services Colleen Foster Minnesota Supercomputing Institute Dr. Ravi Chityala Grant-in-Aid PHS Cancer Center Support Grant P30 CA77398 NIH Grant - 1R01CA , 1R03AR and 1K12-HD Dr. Hui Lab Group Dr. Yutaka Takahashi Dr. Saiful Islam Dr. Leslie Sharkey Dr. Davis Seelig Dr. Masashi Yagi Dr. Taiki Magome Melissa White Dr. Louis Kidder Dr. Susanta Hui 10

11 References Wegrzyn (2010). "Role of Trabecular Microarchitecture and Its Heterogeneity Parameters in the Mechanical Behavior of Ex Vivo Human L3 Vertebrae." Journal of Bone and Mineral Research 25(11): Khoo et al (2009). Comparison of QCT-derived and DXA-derived areal bone mineral density and T scores. Osteoporosis international 20: Kalendar et al (1987). Vertebral Bone Mineral Analysis: An integrated Approach with CT Radiology Goodsitt (1994). "The Composition of Bone Marrow for a Dual-Energy Quantitative Computed Tomography Technique." Investigative Radiology 29(7): Grote (1995). "Intervertebral Variation in Trabecular Microarchitecture Throughout the Normal Spine in Relation to Age." Bone 16(3): Poole (2010). "Changing Structure of the Femoral Neck Across the Adult Female Lifespan." Journal of Bone and Mineral Research 25(3): Huda (1996). "Patient Doses in Bone Mineral Densitometry." The British Journal of Radiology 69: Ericksen et al (1986). Normal and pathological Remodeling of Human trabecular Bone: Three Dimensional Reconstruction of the Remodeling Sequence in Normals and in Metabolic Bone Disease. Endocrine Reviews 7(4): Eloot et al. (2009). MicroCT Performance testing. IFMBE Proceedings Bergmann, P., T. Paternot, and A. Schoutens, Regional measurement of bone calcium accretion rate and exchangeable pool with a wholebody counter: method and studies in subjects without bone disease. Calcif Tissue Int, (1): p Rawlinson, S.C., et al., Adult rat bones maintain distinct regionalized expression of markers associated with their development. PLoS One, (12): p. e8358. Mazess, R.B., Errors in measuring trabecular bone by computed tomography due to marrow and bone composition. Calcif Tissue Int, (2): p Kalender, W., E. Klotz, and C. Suess, Vertebral bone mineral analysis: an integrated approach with CT. Radiology, (2): p

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