Background: Traumatic brachial plexus (BP) injuries may cause loss of elbow flexion. After nerve surgery active elbow flexion often remains insufficient. Muscle strength improvement via cell therapy would be a potential option and could avoid muscle transfer surgery. The primary objective of this pilot study was to assess the safety and feasibility of autologous bone marrow (BM)-derived mononuclear cell (MNC) injection in partly denervated m. biceps brachii of BP patients. Secondary, this study has focused on the myogenic potential of BM-derived MNC by assessing the morphological and functional improvement of the biceps.

Methods: Nine adult BP patients with insufficient force recovery of elbow flexion were included. Three escalating doses (0.9, 4 and 8 * 108) of MNCs were injected in the m. biceps brachii (group A, B and C). In group A, BM was aspirated under local anesthesia (60 ml). In group B and C, BM was aspirated in combination with a muscle tendon transfer (Steindler flexorplasty) under general anesthesia (350 and 650 ml respectively). A muscle biopsy was performed before and 3 months after transplantation. Furthermore, quantitative needle EMG, CT-scan and clinical function was obtained at pre-transplantation and at 3 and 6 months follow-up. The EMG and CT-scan data were blinded during analysis.

Results: No negative side effects were observed. Biopsies showed an increase of 80% in myofiber diameter (P = 0.007), 51% in satellite cells (P = 0.045), 83% in capillary to myofiber ratio (P < 0.001) and a decrease of 51% in fibrosis (P = 0.012). Histological changes were most apparent in group B with an increase of 126% in myofiber diameter (P = 0.019), 100% in capillary to myofiber ratio (P = 0.027), and a decrease of 70% in fibrosis (P = 0.023). EMG demonstrated an increase of 36% in amplitude (P = 0.045), 29% in duration (P = 0.005) and 29% in number of phases of the motor unit potentials (P = 0.002). CT-scan analysis showed a decrease of 48% in mean muscle density (P = 0.009).

Discussion: This study shows that BM-derived MNC transplantation in a partly denervated muscle of traumatic PB patients is safe and feasible. Muscle improvement was observed in muscle biopsies. Furthermore, changes in EMGs and CT-scans were also suggestive for muscle regeneration. The BM dose applied in group B could represent the optimal dose to enhance partly denervated muscles. The results of the present study require confirmation in a placebo-controlled study.

Model-based Roentgen Stereophotogrammetric Analysis (RSA) measures micromotion of an orthopaedic implant with respect to its surrounding bone, without the use of markers on the implant. In previous studies with a total knee prosthesis, Model-based RSA showed to be very accurate. In this study, Model-based RSA is validated in a phantom experiment of a total hip prosthesis.

A metal backed, elliptical shaped EP-FIT PLUS ®cup was used in combination with a SL-PLUS ® hip-stem from PLUS Endoprothetik AG. In vivo conditions were simulated by using sawbones and perspex plates to mimic the bones and soft tissue. Virtual projections of the CAD models of the implant were fitted on the automatically detected contours in nine RSA radiographs and the error inmigration calculation was determined.

The standard deviations of the error in translation for the cup were: 0.03, 0.05, and 0.21 mm. (x, y, z-direction) The standard deviations of the error in orientation were respectively 0.56, 0.48, and 0.18 degrees (n = 10). For the stem, the standard deviations of the error in translation are: 0.09, 0.11, and 0.29 mm and for the orientation: 0.63, 2.03, and 0.24 degrees (n = 0).

The results for the cup are satisfactory, and make Model-based RSA a good alternative for conventional RSA. Especially for this type of metal backed, non hemispherical cup for which no markerless alternative is available. The error in orientation around the y-axis of the stem is of concern. Experiments with models from Reversed Engineering had similar low accuracy. We expect that the cause of these inaccuracies is the rectangular cross sectional shape of this specific hip stem, and we expect better results from experiments with differently shaped stems. The results of this study make very clear that Model-based RSA is avaluable and accurate technique, but phantom studies are always necessary to validate the accuracy for a specific implant shape.

Early micromotion of joint prostheses with respect to the bone can be assessed very accurately by a method called Roentgen Stereophotogrammetric Analysis (RSA); a method that uses two simultaneous X-ray exposures of the joint and has an accuracy of 0.1 mm for translations and 0.3 degree for rotations [1]. In order to reach this accuracy, metallic markers are inserted into the bone and attached to the surface of the prosthesis. These markers can then be identified automatically in the two radiographs [2]. Since the adjustments to the prosthesis are difficult, time-consuming and expensive, RSA has only been applied in a limited number of clinical trials.

In a previous study we have developed a Model-based RSA algorithm, which does not require the attachment of markers to the prosthesis [3]. This algorithm is based on minimisation of the non-overlapping area (NOA) between the automatically detected contour of the prosthesis from the roentgen image, with the virtually projected contour of a three-dimensional model of the prosthesis.

Because the accuracy of this NOA algorithm was not as high as the accuracy of the currently used Marker-based RSA, we have studied alternative algorithms for Model-based RSA. From a simulation study in which we used models of the Interax Total Knee Prosthesis (Stryker-Howmedica) and the G2 Hip Prosthesis (Johnson & John-son), we found that the results of the NOA algorithm can be improved substantially. The newly developed Model-based RSA algorithm is based on minimisation of the mean distance between the points of the actual contour and the virtually projected contour. The simulation study shows that the new algorithm is superior to the NOA-algorithm in situations where part of the contour is occluded, as well as in situations where the contour is distorted by noise. With the new algorithm, the residual position error can be reduced to 0.1 mm. and also the residual orientation error can be reduced to 0.3 degree, making Model-based RSA a future alternative to Marker-based RSA.

To measure micromotion of an orthopaedic implant with respect to its surrounding bone, Roentgen Stereo-photogrammetric Analysis (RSA) was developed. A disadvantage of conventional RSA is that it requires the implant to be marked with tantalum beads. This disadvantage can potentially be resolved with model-based RSA, whereby a 3D model of the implant is used for matching with the actual images and the assessment of position and rotation of the implant. In this study, an improved model-based RSA algorithm is presented and validated in phantom experiments. This algorithm is capable to process projection contours that contain drop-outs. To investigate the influence of the accuracy of the implant models that were used for model-based RSA, we studied both Computer Aided Design (CAD) models as well as models obtained by means of Reversed Engineering (RE) of the actual implant.

The results demonstrate that the RE-models provide more accurate results than the CAD models. If these RE models are derived from the very same implant, it is possible to achieve a maximum standard deviation of the error in the migration calculation of 0.06 mm for translations in x- and y-direction and 0.14 mm for the out of plane z-direction, respectively. For rotations about the y-axis, the standard deviation was about 0.1 degree and for rotations about the x- and z-axis 0.05 degree. For the femur component, it was also possible to reach these accurate results for non-scanned components. The results show that the new algorithm is an improvement with respect to a study we presented earlier [1].

Studies with clinical RSA-radiographs must prove that these results can also be reached in a clinical setting, making model-based RSA a possible alternative for marker-based RSA.