Bone shape difference between control and osteochondral defect groups of the ankle joint.

OBJECTIVE: The etiology of osteochondral defects (OCDs), for which the ankle (talocrural) joint is one of the common sites, is not yet fully understood. In this study, we hypothesized that bone shape plays a role in development of OCDs. Therefore, we quantitatively compared the morphology of the talus and the distal tibia between an OCD group and a control group. METHODS: The shape variations of the talus and distal tibia were described separately by constructing two statistical shape models (SSMs) based on the segmentation of the bones from ankle computed tomography (CT) scans obtained from control (i.e., 35 CT scans) and OCD (i.e., 37 CT scans) groups. The first five modes of shape variation for the SSM corresponding to each bone were statistically compared between control and OCD groups using an analysis of variance (ANOVA) corrected with the Bonferroni for multiple comparisons. RESULTS: The first five modes of variation in the SSMs respectively represented 49% and 40% of the total variance of talus and tibia. Less than 5% of the variance per mode was described by the higher modes. Mode 5 of the talus (P = 0.004) primarily describing changes in the vertical neck angle and Mode 1 of the tibia (P < 0.0001) representing variations at the medial malleolus, showed statistically significant difference between the control and OCD groups. CONCLUSION: Shape differences exist between control and OCD groups. This indicates that a geometry modulated biomechanical behavior of the talocrural joint may be a risk factor for OCD.

EpCAM as multi-tumour target for near-infrared fluorescence guided surgery.

BACKGROUND: Evaluation of resection margins during cancer surgery can be challenging, often resulting in incomplete tumour removal. Fluorescence-guided surgery (FGS) aims to aid the surgeon to visualize tumours and resection margins during surgery. FGS relies on a clinically applicable imaging system in combination with a specific tumour-targeting contrast agent. In this study EpCAM (epithelial cell adhesion molecule) is evaluated as target for FGS in combination with the novel Artemis imaging system. METHODS: The NIR fluorophore IRDye800CW was conjugated to the well-established EpCAM specific monoclonal antibody 323/A3 and an isotype IgG1 as control. The anti-EpCAM/800CW conjugate was stable in serum and showed preserved binding capacity as evaluated on EpCAM positive and negative cell lines, using flow cytometry and cell-based plate assays. Four clinically relevant orthotopic tumour models, i.e. colorectal cancer, breast cancer, head and neck cancer, and peritonitis carcinomatosa, were used to evaluate the performance of the anti-EpCAM agent with the clinically validated Artemis imaging system. The Pearl Impulse small animal imaging system was used as reference. The specificity of the NIRF signal was confirmed using bioluminescence imaging and green-fluorescent protein. RESULTS: All tumour types could clearly be delineated and resected 72 h after injection of the imaging agent. Using NIRF imaging millimetre sized tumour nodules were detected that were invisible for the naked eye. Fluorescence microscopy demonstrated the distribution and tumour specificity of the anti-EpCAM agent. CONCLUSIONS: This study shows the potential of an EpCAM specific NIR-fluorescent agent in combination with a clinically validated intraoperative imaging system to visualize various tumours during surgery.

Characterization and evaluation of the artemis camera for fluorescence-guided cancer surgery.

PURPOSE: Near-infrared (NIR) fluorescence imaging can provide the surgeon with real-time visualization of, e.g., tumor margins and lymph nodes. We describe and evaluate the Artemis, a novel, handheld NIR fluorescence camera. PROCEDURES: We evaluated minimal detectable cell numbers (FaDu-luc2, 7D12-IRDye 800CW), preclinical intraoperative detection of sentinel lymph nodes (SLN) using indocyanine green (ICG), and of orthotopic tongue tumors using 7D12-800CW. Results were compared with the Pearl imager. Clinically, three patients with liver metastases were imaged using ICG. RESULTS: Minimum detectable cell counts for Artemis and Pearl were 2 × 10(5) and 4 × 10(4) cells, respectively. In vivo, seven SLNs were detected in four mice with both cameras. Orthotopic OSC-19-luc2-cGFP tongue tumors were clearly identifiable, and a minimum FaDu-luc2 tumor size of 1 mm(3) could be identified. Six human malignant lesions were identified during three liver surgery procedures. CONCLUSIONS: Based on this study, the Artemis system has demonstrated its utility in fluorescence-guided cancer surgery.

Geometrical adaptation in ulna and radius of cerebral palsy patients: measures and consequences.

BACKGROUND: The presence of significant forearm bone torsion might affect planning and evaluating treatment regimes in cerebral palsy patients. We aimed to evaluate the influence of longstanding wrist flexion, ulnar deviation, and forearm pronation due to spasticity on the bone geometries of radius and ulna. Furthermore, we aimed to model the hypothetical influence of these deformities on potential maximal moment balance for forearm rotation. METHODS: Geometrical measures were determined in hemiplegic cerebral palsy patients (n=5) and healthy controls (n=5). Bilateral differences between the spastic arm and the unaffected side were compared to bilateral differences between the dominant and non-dominant side in the healthy controls. Hypothetical effects of bone torsion on potential maximal forearm rotation moment were calculated using an existing anatomical muscle model. FINDINGS: Patients showed significantly smaller (radius: 41.6%; ulna: 32.9%) and shorter (radius: 9.1%; ulna: 8.4%) forearm bones in the non-dominant arm than in the dominant arm compared to controls (radius: 2.4%; ulna 2.5% and radius: 1.5%; ulna: 1.0% respectively). Furthermore, patients showed a significantly higher torsion angle difference (radius: 24.1°; ulna: 26.2°) in both forearm bones between arms than controls (radius: 2.0°; ulna 1.0°). The model predicted an approximate decrease of 30% of potential maximal supination moment as a consequence of bone torsion. INTERPRETATION: Torsion in the bones of the spastic forearm is likely to influence potential maximal moment balance and thus forearm rotation function. In clinical practice, bone torsion should be considered when evaluating movement limitations especially in children with longstanding spasticity of the upper extremity.

In-vivo dynamic and static three-dimensional joint space distance maps for assessment of cartilage thickness in the radiocarpal joint.

BACKGROUND: The assessment of the joint space thickness is an important clinical parameter for diagnosing osteoarthritis. The accuracy of joint space thickness evaluation from radiographs is limited due to anatomical complexity of the wrist. We propose using distance maps estimated from 3-dimensional and 4-dimensional images reflecting joint space thickness distribution over the relevant part of the articular surface. METHODS: In this paper we investigate the difference between joint space thicknesses acquired from dynamic distance maps to static distance maps. A dynamic distance map gives for every point on a subchondral bone surface the shortest distance to the opposing subchondral bone surface during wrist motion. We hypothesize that the joint space thickness calculated from dynamic distance maps provide a better reflection of the functional joint space thickness. The diagnostic potential of the dynamic joint space thickness measurement is illustrated by comparing data from distance maps of osteoarthritic wrists with normal wrists. FINDINGS: In 10 healthy wrists which are examined, dynamic joint space thickness is smaller than static acquired joint space thickness suggesting that dynamic distance maps provide a better estimate of the measured joint space thickness than joint space thickness based on a static joint space thickness. In 3 examined osteoarthritic wrists the joint space thickness is smaller than in healthy individuals. Moreover, the difference between dynamic and static joint space thickness is smaller in pathological joint parts. INTERPRETATION: The method presented in this paper demonstrates the feasibility of in vivo dynamic distance maps to detect joint space thickness in the radiocarpal joint of healthy individuals.

A three-dimensional analysis of osteoarthritic changes in the thumb carpometacarpal joint.

The purpose of this study is to gain a better understanding of the changes due to osteoarthritis (OA) occurring in the thumb carpometacarpal (CMC) joint by comparing quantitative geometrical measurements in computed tomography scans of healthy and pathological joints in various stages of OA. The measurements were (1) the subluxation of the metacarpal on the trapezium, (2) distance from the scaphoid centre to the metacarpal base, and (3) distance from the metacarpal base to the articulating surface of the trapezium. The three-dimensional position of three characteristic points on the metacarpal, trapezium, and scaphoid were detected in each of the 90 wrists we scanned. The distances between the points were compared by statistical analysis. With high accuracy, we have been able to confirm and quantify that subluxation occurs in the dorso-radial direction. A significant difference in trapezium height and joint space width was found between the OA and control groups. The results indicate how to restore the centre of rotation in surgical treatment of OA with total joint arthroplasty, but the clinical relevance of these findings has to be tested in further clinical studies.

Scaphoid kinematics before and after scaphotrapeziotrapezoidal ligament section. Assessment by radiostereometric analysis and computed tomography in a cadaver study.

The purpose of this study was to measure changes in scaphoid kinematics after division of scaphotrapeziotrapezoidal ligaments, with the intention of determining a clinical measure that could be detected by computed tomography. Twelve freshly frozen cadaver upper extremities were marked with tantalum beads and fixed in positions of neutral, 30° extension, and 40° ulnar deviation. Stereoradiographs for bone migration analysis by radiostereometric analysis and computed tomography scans for visible assessment were obtained before and after scaphotrapeziotrapezoidal ligament section. After ligament resection there was a scaphoid supination of 5° and a small (less than 1 mm) radial, distal, and dorsal translation of the distal pole in 30° of wrist extension. In computed tomography reconstructions, the ligament section appeared as a 1 to 2 mm gap in the scaphotrapeziotrapezoidal corner, with loss of articulation between the distal scaphoid pole and the trapezoid bone and increased scaphoid flexion.