Noninvasive three-dimensional assessment of femoroacetabular impingement

A CT-based method ("HipMotion") for the noninvasive three-dimensional assessment of femoroacetabular impingement (FAI) was developed, validated, and applied in a clinical pilot study. The method allows for the anatomically based calculation of hip range of motion (ROM), the exact location of the impingement zone, and the simulation of quantified surgical maneuvers for FAI. The accuracy of HipMotion was 0.7 +/- 3.1 degrees in a plastic bone setup and -5.0 +/- 5.6 degrees in a cadaver setup. Reliability and reproducibility were excellent [intraclass correlation coefficient (ICC) > 0.87] for all measures except external rotation (ICC = 0.48). The normal ROM was determined from a cohort of 150 patients and was compared to 31 consecutive hips with FAI. Patients with FAI had a significantly decreased flexion, internal rotation, and abduction in comparison to normal hips (p < 0.001). Normal hip flexion and internal rotation are generally overestimated in a number of orthopedic textbooks. HipMotion is a useful tool for further assessment of impinging hips and for appropriate planning of the necessary amount of surgical intervention, which represents the basis for future computer-assisted treatment of FAI with less invasive surgical approaches, such as hip arthroscopy.

Three-dimensional consensus structure of sst2-selective somatostatin (SRIF) antagonists by NMR

The three-dimensional NMR structures of seven octapeptide analogs of somatostatin (SRIF), based on octreotide, with the basic sequence H-Cpa/Phe2-c[DCys3-Xxx7-DTrp/DAph(Cbm)8-Lys9-Thr10-Cys14]-Yyy-NH2 (the numbering refers to the position in native SRIF), with Xxx7 being Aph(Cbm)/Tyr/Agl(NMe,benzoyl) and Yyy being Nal/DTyr/Thr, are presented here. Most of these analogs exhibit potent and highly selective binding to sst2 receptors, and all of the analogs are antagonists inhibiting receptor signaling. Based on their consensus 3D structure, the pharmacophore of the sst2-selective antagonist has been defined. The pharmacophore involves the side chains of Cpa2, DTrp/DAph(Cbm)8, and Lys9, with the backbone for most of the sst2-selective antagonists comprised a Type-II' beta-turn. Hence, the sst2-selective antagonist pharmacophore is very similar to the sst2-selective agonist pharmacophore previously described.

Experimental model to evaluate in vivo and in vitro cartilage MR imaging by means of histological analyses

OBJECTIVES: Implementation of an experimental model to compare cartilage MR imaging by means of histological analyses. MATERIAL AND METHODS: MRI was obtained from 4 patients expecting total knee replacement at 1.5 and/or 3T prior surgery. The timeframe between pre-op MRI and knee replacement was within two days. Resected cartilage-bone samples were tagged with Ethi((R))-pins to reproduce the histological cutting course. Pre-operative scanning at 1.5T included following parameters for fast low angle shot (FLASH: TR/TE/FA=33ms/6ms/30 degrees , BW=110kHz, 120mmx120mm FOV, 256x256 matrix, 0.65mm slice-thickness) and double echo steady state (DESS: TR/TE/FA=23.7ms/6.9ms/40 degrees , BW=130kHz, 120x120mm FOV, 256x256 matrix, 0.65mm slice-thickness). At 3T, scan parameters were: FLASH (TR/TE/FA=12.2ms/5.1ms/10 degrees , BW=130kHz, 170x170mm FOV, 320x320, 0.5mm slice-thickness) and DESS (TR/TE/FA=15.6ms/4.5ms/25 degrees , BW=200kHz, 135mmx150mm FOV, 288x320matrix, 0.5mm slice-thickness). Imaging of the specimens was done the same day at 1.5T. MRI (Noyes) and histological (Mankin) score scales were correlated using the paired t-test. Sensitivity and specificity for the detection of different grades of cartilage degeneration were assessed. Inter-reader and intra-reader reliability was determined using Kappa analysis. RESULTS: Low correlation (sensitivity, specificity) was found for both sequences in normal to mild Mankin grades. Only moderate to severe changes were diagnosed with higher significance and specificity. The use of higher field-strengths was advantageous for both protocols with sensitivity values ranging from 13.6% to 93.3% (FLASH) and 20.5% to 96.2% (DESS). Kappa values ranged from 0.488 to 0.944. CONCLUSIONS: Correlating MR images with continuous histological slices was feasible by using three-dimensional imaging, multi-planar-reformat and marker pins. The capability of diagnosing early cartilage changes with high accuracy could not be proven for both FLASH and DESS.

A rare anomaly of the anterior communicating artery complex hidden by a large broad-neck aneurysm and disclosed by three-dimensional rotational angiography

Double fenestration of the anterior communicating artery (ACoA) complex associated with an aneurysm is a very rare finding and is usually caused by ACoA duplication and the presence of a median artery of the corpus callosum (MACC). We present a patient in whom double fenestration was not associated with ACoA duplication or even with MACC, representing therefore, a previously unreported anatomic variation. A 43 year old woman experienced sudden headache and the CT scans showed subarachnoid haemorrhage (SAH). On admission, her clinical condition was consistent with Hunt and Hess grade II. Conventional digital subtraction angiography (DSA) was performed and revealed multiple intracranial aneurysms arising from both middle cerebral arteries (MCA) and from the ACoA. Three-dimensional rotational angiography (3D-RA) disclosed a double fenestration of the ACoA complex which was missed by DSA. The patient underwent a classic pterional approach in order to achieve occlusion of both left MCA and ACoA aneurysms by surgical clipping. The post-operative period was uneventful. A rare anatomical variation characterised by a double fenestration not associated with ACoA duplication or MACC is described. The DSA images missed the double fenestration which was disclosed by 3D-RA, indicating the importance of 3D-RA in the diagnosis and surgical planning of intracranial aneurysms.

Conformationally homogeneous heterocyclic pseudotetrapeptides as three-dimensional scaffolds for rational drug design: receptor-selective somatostatin analogues

A would-be amide: A 1,4-disubstituted 1,2,3-triazole was used as a surrogate for a trans amide bond to create a library of 16 diastereomeric pseudotetrapeptides as beta-turn mimetics. High-resolution structural analysis indicated that these scaffolds adopt distinct, rigid, conformationally homogeneous beta-turn-like structures (see example), some of which bind somatostatin receptor subtypes selectively, and some of which show broad-spectrum activity.

Feasibility of T2* mapping for the evaluation of hip joint cartilage at 1.5T using a three-dimensional (3D), gradient-echo (GRE) sequence: a prospective study

This study defines the feasibility of utilizing three-dimensional (3D) gradient-echo (GRE) MRI at 1.5T for T(2)* mapping to assess hip joint cartilage degenerative changes using standard morphological MR grading while comparing it to delayed gadolinium-enhanced MRI of cartilage (dGEMRIC). MRI was obtained from 10 asymptomatic young adult volunteers and 33 patients with symptomatic femoroacetabular impingement (FAI). The protocol included T(2)* mapping without gadolinium-enhancement utilizing a 3D-GRE sequence with six echoes, and after gadolinium injection, routine hip sequences, and a dual-flip-angle 3D-GRE sequence for dGEMRIC T(1) mapping. Cartilage was classified as normal, with mild changes, or with severe degenerative changes based on morphological MRI. T(1) and T(2)* findings were subsequently correlated. There were significant differences between volunteers and patients in normally-rated cartilage only for T(1) values. Both T(1) and T(2)* values decreased significantly with the various grades of cartilage damage. There was a statistically significant correlation between standard MRI and T(2)* (T(1)) (P < 0.05). High intraclass correlation was noted for both T(1) and T(2)*. Correlation factor was 0.860 to 0.954 (T(2)*-T(1) intraobserver) and 0.826 to 0.867 (T(2)*-T(1) interobserver). It is feasible to gather further information about cartilage status within the hip joint using GRE T(2)* mapping at 1.5T.

A comparison between two-dimensional and three-dimensional cephalometry on frontal radiographs and on cone beam computed tomography scans of human skulls

The aim of this study was to evaluate whether measurements performed on conventional frontal radiographs are comparable to measurements performed on three-dimensional (3D) models of human skulls derived from cone beam computed tomography (CBCT) scans and if the latter can be used in longitudinal studies. Cone beam computed tomography scans and conventional frontal cephalometric radiographs were made of 40 dry human skulls. From the CBCT scan a 3D model was constructed. Standard cephalometric software was used to identify landmarks and to calculate ratios and angles. The same operator identified 10 landmarks on both types of cephalometric radiographs, and on all images, five times with a time interval of 1 wk. Intra-observer reliability was acceptable for all measurements. There was a statistically significant and clinically relevant difference between measurements performed on conventional frontal radiographs and on 3D CBCT-derived models of the same skull. There was a clinically relevant difference between angular measurements performed on conventional frontal cephalometric radiographs, compared with measurements performed on 3D models constructed from CBCT scans. We therefore recommend that 3D models should not be used for longitudinal research in cases where there are only two-dimensional (2D) records from the past.

BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium-derived progenitor cells cultured in three-dimensional alginate hydrogel

OBJECTIVE: According to recent reports, the synovial membrane may contain mesenchymal stem cells with the potential to differentiate into chondrocytes under appropriate conditions. In order to assess the usefulness of synovium-derived progenitor cells for the purposes of cartilage tissue engineering, we explored their requirements for the expression of chondrocyte-specific genes after expansion in vitro. DESIGN: Mesenchymal progenitor cells were isolated from the synovial membranes of bovine shoulder joints and expanded in two-dimensions on plastic surfaces. They were then seeded either as micromass cultures or as single cells within alginate gels, which were cultured in serum-free medium. Under these three-dimensional conditions, chondrogenesis is known to be supported and maintained. Cell cultures were exposed either to bone morphogenetic protein-2 (BMP-2) or to isoforms of transforming growth factor-beta (TGF-beta). The levels of mRNA for Sox9, collagen types I and II and aggrecan were determined by RT-PCR. RESULTS: When transferred to alginate gel cultures, the fibroblast-like synovial cells assumed a rounded form. BMP-2, but not isoforms of TGF-beta, stimulated, in a dose-dependent manner, the production of messenger RNAs (mRNAs) for Sox9, type II collagen and aggrecan. Under optimal conditions, the expression levels of cartilage-specific genes were comparable to those within cultured articular cartilage chondrocytes. However, in contrast to cultured articular cartilage chondrocytes, synovial cells exposed to BMP-2 continued to express the mRNA for alpha1(I) collagen. CONCLUSIONS: This study demonstrates that bovine synovium-derived mesenchymal progenitor cells can be induced to express chondrocyte-specific genes. However, the differentiation process is not complete under the chosen conditions. The stimulation conditions required for full transformation must now be delineated.