title: Integrated multimodal imaging of dynamic bone-tumor alterations associated with metastatic prostate cancer.
abstract: Bone metastasis occurs for men with advanced prostate cancer which promotes osseous growth and destruction driven by alterations in osteoblast and osteoclast homeostasis. Patients can experience pain, spontaneous fractures and morbidity eroding overall quality of life. The complex and dynamic cellular interactions within the bone microenvironment limit current treatment options thus prostate to bone metastases remains incurable. This study uses voxel-based analysis of diffusion-weighted MRI and CT scans to simultaneously evaluate temporal changes in normal bone homeostasis along with prostate bone metatastsis to deliver an improved understanding of the spatiotemporal local microenvironment. Dynamic tumor-stromal interactions were assessed during treatment in mouse models along with a pilot prospective clinical trial with metastatic hormone sensitive and castration resistant prostate cancer patients with bone metastases. Longitudinal changes in tumor and bone imaging metrics during delivery of therapy were quantified. Studies revealed that voxel-based parametric response maps (PRM) of DW-MRI and CT scans could be used to quantify and spatially visualize dynamic changes during prostate tumor growth and in response to treatment thereby distinguishing patients with stable disease from those with progressive disease (p<0.05). These studies suggest that PRM imaging biomarkers are useful for detection of the impact of prostate tumor-stromal responses to therapies thus demonstrating the potential of multi-modal PRM image-based biomarkers as a novel means for assessing dynamic alterations associated with metastatic prostate cancer. These results establish an integrated and clinically translatable approach which can be readily implemented for improving the clinical management of patients with metastatic bone disease.
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Jean-Christophe
authors: JC
authors: Brisset
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Benjamin A
authors: BA
authors: Hoff
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Thomas L
authors: TL
authors: Chenevert
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Jon A
authors: JA
authors: Jacobson
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Jennifer L
authors: JL
authors: Boes
authors: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Stefanie
authors: S
authors: Galbán
authors: Department of Radiation Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Alnawaz
authors: A
authors: Rehemtulla
authors: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Timothy D
authors: TD
authors: Johnson
authors: Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Kenneth J
authors: KJ
authors: Pienta
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Craig J
authors: CJ
authors: Galbán
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Charles R
authors: CR
authors: Meyer
authors: Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Timothy
authors: T
authors: Schakel
authors: Department of Biomedical Engineering, Eindhoven University of Technology, Eindhoven, The Netherlands.
authors: Klaas
authors: K
authors: Nicolay
authors: Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Ajjai S
authors: AS
authors: Alva
authors: Division of Hematology/Oncology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Maha
authors: M
authors: Hussain
authors: Department of Radiology, University of Michigan, Ann Arbor, Michigan, United States of America.
authors: Brian D
authors: BD
authors: Ross
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D015519:Bone Density; D001859:Bone Neoplasms / Q000175:diagnosis* / Q000556:secondary* / Q000628:therapy; D038524:Diffusion Magnetic Resonance Imaging; D004164:Diphosphonates / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D000077143:Docetaxel; D006801:Humans; D008297:Male; D051379:Mice; D064847:Multimodal Imaging / Q000379:methods*; D010006:Osteoblasts / Q000187:drug effects / Q000378:metabolism; D010014:Osteolysis / Q000175:diagnosis; D011471:Prostatic Neoplasms / Q000473:pathology*; D043823:Taxoids / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000970:Antineoplastic Agents; D004164:Diphosphonates; D043823:Taxoids; D000077143:Docetaxel