# An Anatomical-Based Subject-Specific Model of In-Vivo Knee Joint 3D Kinematics From Medical Imaging
## 4 Discussions
The sensitivity of the model results with respect to the techniques used for MRI-CT and CT-3 DV registration was not analysed. For instance, fiducial points were used in this study for MRI-CT registration, since they are standard, simple, and applied in many clinical procedures, in particular when aligning bony landmarks. However, many other techniques have been proposed, like mutual information and iterative-closest-point techniques [31; 33]. The use of fiducial points for MRI-CT registration showed a good accuracy in a previous investigation [31], with a mean distance between corresponding surfaces lower than 2 mm, consistent with the accuracy of the medical imaging techniques used in the present study. Since one of the scopes of geometry optimization is to limit the influence of both the segmentation and registration inaccuracies, the effect of a different registration technique on the results is believed to be small. The joint model is rigid (i.e., no deformation is allowed to the ligaments) since it relies on the isometric behaviour observed for the ligaments during the joint natural motion [4; 8; 9; 10; 11]. However, rigid models are often considered in multibody simulations to reduce computational and numerical issues in dynamic analyses [2]. Moreover, as far as ligament elongation is of interest to discern the different joint behaviours under changing loading conditions, ligament and contact compliance can still be easily added in the model in a simple and computationally efficient way [42]. The joint natural motion was used as a reference for the model definition. It is indeed a simple and repeatable motion that can be easily performed within a fluoroscope. Moreover, it proved to be a good reference to represent also other physiologically loaded motions [43]. Finally, the proposed procedure required a measure of a reference motion for the model definition. However, it is firstly remarkable that the model is still able to describe the experimental motion with good accuracy despite the anatomical constraints are rigid and very close to the measured anatomy. Secondly, this is actually one of the features of the proposed procedure: it extends the standard method which imposes a given motion at the joint, by adding also information on the subject articular constraints in a simple and computationally efficient way. In conclusion, the proposed procedure allows the definition in vivo of a subject-specific spatial model of the knee, including also the patello-femoral joint, which reproduces both the anatomical constraints and the natural joint motion of the subject. The accuracy and the overall validation were determined on a volunteer. The result is valuable since it allows the development of a methodological procedure to specialize the model on a specific patient, to be exploited in the future for personalized prosthesis design and medical procedures, as well as for the definition of more detailed, reliable and customized musculoskeletal models of the lower limb. **Author Contributions:** Each author contribution to the article is subdivided as follows: conceptualization, N.S. and V.P.-C.; methodology, N.S., F.N., C.B. V.P.-C. and A.L. ; software, F.N., N.S and M.C. ; validation, F.N. and C.B. ; formal analysis, N.S. and F.N. and M.C. ; investigation, F.N., C.B., N.S., V.P.-C., A.L. and S.D. ; resources, V.P.-C. and A.L. ; writing-original draft preparation, F.N. ; writing-review and editing, N.S., C.B., A.L. and M.C. ; visualization, F.N. ; supervision, V.P and A.L. ; project administration, V.P.-C. and A.L. ; funding acquisition, V.P.-C. and A.L. All authors have read and agreed to the published version of the manuscript. **Funding:** This research received no external funding. **Conflicts of Interest:** None of the authors have any conflict of interest with the subject matter of this manuscript.