Co-registration of multi-modality imaging allows for comprehensive analysis of tumor-induced bone disease.
Bone metastases are a clinically significant problem that arises in approximately 70% of metastatic breast cancer patients. Once established in the bone, tumor cells induce changes in the bone microenvironment that lead to bone destruction, pain, and significant morbidity. While much is known about the later stages of bone disease, less is known about the earlier stages or the changes in protein expression in the tumor micro-environment. Due to promising results of combining magnetic resonance imaging (MRI) and Matrix-Assisted Laser Desorption/Ionization Imaging Mass Spectrometry (MALDI IMS) ion images in the brain, we developed methods for applying these modalities to models of tumor-induced bone disease in order to better understand the changes in protein expression that occur within the tumor-bone microenvironment. Specifically, we integrated 3-dimensional-volume reconstructions of spatially resolved MALDI IMS with high-resolution anatomical and diffusion weighted MRI data and histology in an intratibial model of breast tumor-induced bone disease. This approach enables us to analyze proteomic profiles from MALDI IMS data with corresponding in vivo imaging and ex vivo histology data. To the best of our knowledge, this is the first time that these three modalities have been rigorously registered in the bone. The MALDI mass-to-charge ratio peaks indicate differential expression of calcyclin, ubiquitin, and other proteins within the tumor cells, while peaks corresponding to hemoglobin A and calgranulin A provided molecular information that aided in the identification of areas rich in red and white blood cells, respectively. This multi-modality approach will allow us to comprehensively understand the bone-tumor microenvironment and thus may allow us to better develop and test approaches for inhibiting bone metastases.
Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN, USA.
Erin H
EH
Seeley
Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA.
Kevin J
KJ
Wilson
Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA; Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Physics and Astronomy, Vanderbilt University, Nashville, TN, USA.
Thomas E
TE
Yankeelov
Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, TN, USA.
Rachelle W
RW
Johnson
Vanderbilt University Institute of Imaging Science, Vanderbilt University, Nashville, TN, USA; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN, USA; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN, USA; Physics and Astronomy, Vanderbilt University, Nashville, TN, USA.
John C
JC
Gore
Mass Spectrometry Research Center, Vanderbilt University, Nashville, TN, USA; Department of Biochemistry, Vanderbilt University, Nashville, TN, USA; Department of Chemistry, Vanderbilt University, Nashville, TN, USA; Department of Medicine, Vanderbilt University, Nashville, TN, USA.
Richard M
RM
Caprioli
Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA.
Lynn M
LM
Matrisian
Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA; Department of Veterans Affairs, Tennessee Valley Healthcare System, Vanderbilt University, Nashville, TN, USA; Vanderbilt Center for Bone Biology, Vanderbilt University, Nashville, TN, USA; Department of Medicine, Vanderbilt University, Nashville, TN, USA. Electronic address: julie.sterling@vanderbilt.edu.
Julie A
JA
Sterling
D000818:Animals; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000556:secondary*; D001943:Breast Neoplasms / Q000556:secondary; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods*; D009362:Neoplasm Metastasis / Q000175:diagnosis; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods*
Bone; Image co-registration; MALDI; MRI; Metastases