title: Application of surface roughness analysis on micro-computed tomographic images of bone erosion: examples using a rodent model of rheumatoid arthritis.
abstract: Quantifying the bone erosion in preclinical models of rheumatoid arthritis is valuable for the evaluation of drug treatments. This study introduces a three-dimensional method for bone surface roughness measurement from micro-computed tomographic data obtained from rats subjected to collagen-induced arthritis (CIA), in which the degree of bone erosion is related to the severity and the duration of the disease. In two studies of rat CIA, the surface roughness of the talus bone following 21 days of disease increased 559% and 486% from the control group. At 41 days following disease induction, the roughness of the bone surface increased 857% above baseline. The roughness of the control samples was similar from each study (less than 4% different), demonstrating the robustness of the algorithm. Treatment with methotrexate at 0.1 mg/kg daily demonstrated significant protection from bone erosion, whereas the 0.05 mg/kg daily dose was not efficacious (98% versus 22% inhibition of roughness-measured bone erosion). The main advantage of such an algorithm is demonstrated in the preclinical drug study of rat CIA with methotrexate treatment, indicating the immediate utility of this approach in drug development studies.
authors.affiliation: Department of Imaging Sciences, Millennium Pharmaceuticals, Inc., Cambridge, MA 02139, USA. matt.silva@mpi.com
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Silva
authors.forename: Jason
authors.initials: J
authors.lastname: Ruan
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Siebert
authors.forename: Anneli
authors.initials: A
authors.lastname: Savinainen
authors.forename: Bruce
authors.initials: B
authors.lastname: Jaffee
authors.forename: Lisa
authors.initials: L
authors.lastname: Schopf
authors.forename: Sudeep
authors.initials: S
authors.lastname: Chandra
mesh_terms: D000465:Algorithms; D000818:Animals; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging; D001842:Bone and Bones / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008953:Models, Anatomic; D019047:Phantoms, Imaging; D051381:Rats; D011917:Rats, Inbred Lew; D013499:Surface Properties; D014057:Tomography, X-Ray Computed / Q000379:methods*
chemical_list: D007166:Immunosuppressive Agents; D008727:Methotrexate