Three-dimensional magnetic resonance observation of cartilage repair tissue (MOCART) score assessed with an isotropic three-dimensional true fast imaging with steady-state precession sequence at 3.0 Tesla

INTRODUCTION: Cartilage defects are common pathologies and surgical cartilage repair shows promising results. In its postoperative evaluation, the magnetic resonance observation of cartilage repair tissue (MOCART) score, using different variables to describe the constitution of the cartilage repair tissue and the surrounding structures, is widely used. High-field magnetic resonance imaging (MRI) and 3-dimensional (3D) isotropic sequences may combine ideal preconditions to enhance the diagnostic performance of cartilage imaging.Aim of this study was to introduce an improved 3D MOCART score using the possibilities of an isotropic 3D true fast imaging with steady-state precession (True-FISP) sequence in the postoperative evaluation of patients after matrix-associated autologous chondrocyte transplantation (MACT) as well as to compare the results to the conventional 2D MOCART score using standard MR sequences. MATERIAL AND METHODS: The study had approval by the local ethics commission. One hundred consecutive MR scans in 60 patients at standard follow-up intervals of 1, 3, 6, 12, 24, and 60 months after MACT of the knee joint were prospectively included. The mean follow-up interval of this cross-sectional evaluation was 21.4 +/- 20.6 months; the mean age of the patients was 35.8 +/- 9.4 years. MRI was performed at a 3.0 Tesla unit. All variables of the standard 2D MOCART score where part of the new 3D MOCART score. Furthermore, additional variables and options were included with the aims to use the capabilities of isotropic MRI, to include the results of recent studies, and to adapt to the needs of patients and physician in a clinical routine examination. A proton-density turbo spin-echo sequence, a T2-weighted dual fast spin-echo (dual-FSE) sequence, and a T1-weighted turbo inversion recovery magnitude (TIRM) sequence were used to assess the standard 2D MOCART score; an isotropic 3D-TrueFISP sequence was prepared to evaluate the new 3D MOCART score. All 9 variables of the 2D MOCART score were compared with the corresponding variables obtained by the 3D MOCART score using the Pearson correlation coefficient; additionally the subjective quality and possible artifacts of the MR sequences were analyzed. RESULTS: The correlation between the standard 2D MOCART score and the new 3D MOCART showed for the 8 variables "defect fill," "cartilage interface," "surface," "adhesions," "structure," "signal intensity," "subchondral lamina," and "effusion"-a highly significant (P < 0.001) correlation with a Pearson coefficient between 0.566 and 0.932. The variable "bone marrow edema" correlated significantly (P < 0.05; Pearson coefficient: 0.257). The subjective quality of the 3 standard MR sequences was comparable to the isotropic 3D-TrueFISP sequence. Artifacts were more frequently visible within the 3D-TrueFISP sequence. CONCLUSION: In the clinical routine follow-up after cartilage repair, the 3D MOCART score, assessed by only 1 high-resolution isotropic MR sequence, provides comparable information than the standard 2D MOCART score. Hence, the new 3D MOCART score has the potential to combine the information of the standard 2D MOCART score with the possible advantages of isotropic 3D MRI at high-field. A clear limitation of the 3D-TrueFISP sequence was the high number of artifacts. Future studies have to prove the clinical benefits of a 3D MOCART score.

Diagnostic performance and accuracy of 3-D spoiled gradient-dual-echo MRI with water- and fat-signal separation in liver-fat quantification: comparison to liver biopsy

To prospectively evaluate a 3-dimensional spoiled gradient-dual-echo (3D SPGR-DE) magnetic resonance imaging (MRI) sequence for the qualitative and quantitative analysis of liver fat content (LFC) in patients with the suspicion of fatty liver disease using histopathology as the standard of reference.

Effects of anatomic conformation on three-dimensional motion of the caudal lumbar and lumbosacral portions of the vertebral column of dogs

OBJECTIVE: To determine the association between the 3-dimensional (3-D) motion pattern of the caudal lumbar and lumbosacral portions of the canine vertebral column and the morphology of vertebrae, facet joints, and intervertebral disks. SAMPLE POPULATION: Vertebral columns of 9 German Shepherd Dogs and 16 dogs of other breeds with similar body weights and body conditions. PROCEDURE: Different morphometric parameters of the vertebral column were assessed by computed tomography (CT) and magnetic resonance imaging. Anatomic conformation and the 3-D motion pattern were compared, and correlation coefficients were calculated. RESULTS: Total range of motion for flexion and extension was mainly associated with the facet joint angle, the facet joint angle difference between levels of the vertebral column in the transverse plane on CT images, disk height, and lever arm length. CONCLUSIONS AND CLINICAL RELEVANCE: Motion is a complex process that is influenced by the entire 3-D conformation of the lumbar portion of the vertebral column. In vivo dynamic measurements of the 3-D motion pattern of the lumbar and lumbosacral portions of the vertebral column will be necessary to further assess biomechanics that could lead to disk degeneration in dogs.

Evaluation of magnetic resonance colonography at 3.0 Tesla regarding diagnostic accuracy and image quality

OBJECTIVES: To assess magnetic resonance (MR)-colonography (MRC) for detection of colorectal lesions using two different T1w three-dimensional (3D)-gradient-recalled echo (GRE)-sequences and integrated parallel data acquisition (iPAT) at a 3.0 Tesla MR-unit. MATERIALS AND METHODS: In this prospective study, 34 symptomatic patients underwent dark lumen MRC at a 3.0 Tesla unit before conventional colonoscopy (CC). After colon distension with tap water, 2 high-resolution T1w 3D-GRE [3-dimensional fast low angle shot (3D-FLASH), iPAT factor 2 and 3D-volumetric interpolated breathhold examination (VIBE), iPAT 3] sequences were acquired without and after bolus injection of gadolinium. Prospective evaluation of MRC was performed. Image quality of the different sequences was assessed qualitatively and quantitatively. The findings of the same day CC served as standard of reference. RESULTS: MRC identified all polyps >5 mm (16 of 16) in size and all carcinomas (4 of 4) correctly. Fifty percent of the small polyps 0.6). CONCLUSIONS: MRC using 3D-GRE-sequences and iPAT is feasible at 3.0 T-systems. The high-resolution 3D-FLASH was slightly preferred over the 3D-VIBE because of better image quality, although both used sequences showed no statistical significant difference.

Quantitative comparison of 3 enamel-stripping devices in vitro: how precisely can we strip teeth?

INTRODUCTION In this in-vitro study, we aimed to investigate the predictability of the expected amount of stripping using 3 common stripping devices on premolars. METHODS One hundred eighty extracted premolars were mounted and aligned in silicone. Tooth mobility was tested with Periotest (Medizintechnik Gulden, Modautal, Germany) (8.3 ± 2.8 units). The selected methods for interproximal enamel reduction were hand-pulled strips (Horico, Hapf Ringleb & Company, Berlin, Germany), oscillating segmental disks (O-drive-OD 30; KaVo Dental, Biberach, Germany), and motor-driven abrasive strips (Orthofile; SDC Switzerland, Lugano-Grancia, Switzerland). With each device, the operator intended to strip 0.1, 0.2, 0.3, or 0.4 mm on the mesial side of 15 teeth. The teeth were scanned before and after stripping with a 3-dimensional laser scanner. Superposition and measurement of stripped enamel on the most mesial point of the tooth were conducted with Viewbox software (dHal Software, Kifissia, Greece). The Wilcoxon signed rank test and the Kruskal-Wallis test were applied; statistical significance was set at alpha ≤ 0.05. RESULTS Large variations between the intended and the actual amounts of stripped enamel, and between stripping procedures, were observed. Significant differences were found at 0.1 mm of intended stripping (P ≤ 0.05) for the hand-pulled method and at 0.4 mm of intended stripping (P ≤ 0.001 to P = 0.05) for all methods. For all scenarios of enamel reduction, the actual amount of stripping was less than the predetermined and expected amount of stripping. The Kruskal-Wallis analysis showed no significant differences between the 3 methods. CONCLUSIONS There were variations in the stripped amounts of enamel, and the stripping technique did not appear to be a significant predictor of the actual amount of enamel reduction. In most cases, actual stripping was less than the intended amount of enamel reduction.

Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway

Adaptive immune responses are characterized by substantial restructuring of secondary lymphoid organs. The molecular and cellular factors responsible for virus-induced lymphoid remodeling are not well known to date. Here we applied optical projection tomography, a mesoscopic imaging technique, for a global analysis of the entire 3-dimensional structure of mouse peripheral lymph nodes (PLNs), focusing on B-cell areas and high endothelial venule (HEV) networks. Structural homeostasis of PLNs was characterized by a strict correlation between total PLN volume, B-cell volume, B-cell follicle number, and HEV length. After infection with lymphocytic choriomeningitis virus, we observed a substantial, lymphotoxin (LT) beta-receptor-dependent reorganization of the PLN microarchitecture, in which an initial B-cell influx was followed by 3-fold increases in PLN volume and HEV network length on day 8 after infection. Adoptive transfer experiments revealed that virus-induced PLN and HEV network remodeling required LTalpha(1)beta(2)-expressing B cells, whereas the inhibition of vascular endothelial growth factor-A signaling pathways had no significant effect on PLN expansion. In summary, lymphocytic choriomeningitis virus-induced PLN growth depends on a vascular endothelial growth factor-A-independent, LT- and B cell-dependent morphogenic pathway, as revealed by an in-depth mesoscopic analysis of the global PLN structure.

Critical roles for Rac GTPases in T-cell migration to and within lymph nodes

Naive T cells continuously recirculate between secondary lymphoid tissue via the blood and lymphatic systems, a process that maximizes the chances of an encounter between a T cell and its cognate antigen. This recirculation depends on signals from chemokine receptors, integrins, and the sphingosine-1-phosphate receptor. The authors of previous studies in other cell types have shown that Rac GTPases transduce signals leading to cell migration and adhesion; however, their roles in T cells are unknown. By using both 3-dimensional intravital and in vitro approaches, we show that Rac1- and Rac2-deficient T cells have multiple defects in this recirculation process. Rac-deficient T cells home very inefficiently to lymph nodes and the white pulp of the spleen, show reduced interstitial migration within lymph node parenchyma, and are defective in egress from lymph nodes. These mutant T cells show defective chemokine-induced chemotaxis, chemokinesis, and adhesion to integrin ligands. They have reduced lateral motility on endothelial cells and transmigrate in-efficiently. These multiple defects stem from critical roles for Rac1 and Rac2 in transducing chemokine and sphingosine-1-phosphate receptor 1 signals leading to motility and adhesion.

Feasibility of image-guided radiotherapy based on tomotherapy for the treatment of locally advanced anal carcinoma

The standard of care for locally advanced anal cancer has been concurrent chemoradiation. However, conventional treatment with 3-dimensional radiotherapy is associated with significant toxicity. The feasibility of new radiotherapy techniques such as image-guided radiotherapy (IGRT) in combination with chemotherapy for the treatment of this malignancy was assessed.

Computer-assisted femoral head-neck osteochondroplasty using a surgical milling device an in vitro accuracy study

Surgical navigation might increase the safety of osteochondroplasty procedures in patients with femoroacetabular impingement. Feasibility and accuracy of navigation of a surgical reaming device were assessed. Three-dimensional models of 18 identical sawbone femora and 5 cadaver hips were created. Custom software was used to plan and perform repeated computer-assisted osteochondroplasty procedures using a navigated burr. Postoperative 3-dimensional models were created and compared with the preoperative models. A Bland-Altmann analysis assessing α angle and offset ratio accuracy showed even distribution along the zero line with narrow confidence intervals. No differences in α angle and offset ratio accuracy (P = 0.486 and P = 0.2) were detected between both observers. Planning and conduction of navigated osteochondroplasty using a surgical reaming device is feasible and accurate.

Statistical modeling of the eye for multimodal treatment planning for external beam radiation therapy of intraocular tumors

Ocular anatomy and radiation-associated toxicities provide unique challenges for external beam radiation therapy. For treatment planning, precise modeling of organs at risk and tumor volume are crucial. Development of a precise eye model and automatic adaptation of this model to patients' anatomy remain problematic because of organ shape variability. This work introduces the application of a 3-dimensional (3D) statistical shape model as a novel method for precise eye modeling for external beam radiation therapy of intraocular tumors.

DOCK8 is a Cdc42 activator critical for interstitial dendritic cell migration during immune responses

To migrate efficiently through the interstitium, dendritic cells (DCs) constantly adapt their shape to the given structure of the extracellular matrix and follow the path of least resistance. It is known that this amoeboid migration of DCs requires Cdc42, yet the upstream regulators critical for localization and activation of Cdc42 remain to be determined. Mutations of DOCK8, a member of the atypical guanine nucleotide exchange factor family, causes combined immunodeficiency in humans. In the present study, we show that DOCK8 is a Cdc42-specific guanine nucleotide exchange factor that is critical for interstitial DC migration. By generating the knockout mice, we found that in the absence of DOCK8, DCs failed to accumulate in the lymph node parenchyma for T-cell priming. Although DOCK8-deficient DCs migrated normally on 2-dimensional surfaces, DOCK8 was required for DCs to crawl within 3-dimensional fibrillar networks and to transmigrate through the subcapsular sinus floor. This function of DOCK8 depended on the DHR-2 domain mediating Cdc42 activation. DOCK8 deficiency did not affect global Cdc42 activity. However, Cdc42 activation at the leading edge membrane was impaired in DOCK8-deficient DCs, resulting in a severe defect in amoeboid polarization and migration. Therefore, DOCK8 regulates interstitial DC migration by controlling Cdc42 activity spatially.

Evaluation of radial distribution of cartilage degeneration and necessity of pre-contrast measurements using radial dGEMRIC in adults with acetabular dysplasia

Background The purpose of the present study was to investigate the radial distribution patterns of cartilage degeneration in dysplastic hips at different stages of secondary osteoarthritis (OA) by using radial delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC), and to assess whether pre-contrast measurements are necessary. Methods Thirty-five hips in 21 subjects (mean age ± SD, 27.6 ± 10.8 years) with acetabular dysplasia (lateral CE angle < 25°) were studied. Severity of OA was assessed on radiographs using Tönnis grading. Pre- (T1pre) and post-contrast T1 (T1Gd) values were measured at 7 sub-regions on radial reformatted slices acquired from a 3-dimensional (3D) T1 mapping sequence using a 1.5 T MR scanner. Values of radial T1pre, T1Gd and ΔR1 (1/T1Gd - 1/T1pre) of subgroups with different severity of OA were compared to those of the subgroup without OA using nonparametric tests, and bivariate linear Pearson correlations between radial T1Gd and ΔR1 were analyzed for each subgroup. Results Compared to the subgroup without OA, the subgroup with mild OA was observed with a significant decrease in T1Gd in the anterosuperior to superior sub-regions (mean, 476 ~ 507 ms, p = 0.026 ~ 0.042) and a significant increase in ΔR1 in the anterosuperior to superoposterior and posterior sub-regions (mean, 0.93 ~ 1.37 s-1, p = 0.012 ~ 0.042). The subgroup with moderate to severe OA was observed with a significant overall decrease in T1Gd (mean, 404 ~ 452 ms, p = 0.001 ~ 0.020) and an increase in ΔR1 (mean, 1.17 ~1.69 s-1, p = 0.001 ~ 0.020). High correlations were observed between radial T1Gd and ΔR1 for all subgroups (r = −0.869 ~ −0.944, p < 0.001). Conclusions Radial dGEMRIC without pre-contrast measurements is useful for evaluating different patterns of cartilage degeneration in the entire hip joint of patients with hip dysplasia, particularly for those in early stages of secondary OA.

Automatic extraction of the mid-facial plane for cranio-maxillofacial surgery planning

Recently developed computer applications provide tools for planning cranio-maxillofacial interventions based on 3-dimensional (3D) virtual models of the patient's skull obtained from computed-tomography (CT) scans. Precise knowledge of the location of the mid-facial plane is important for the assessment of deformities and for planning reconstructive procedures. In this work, a new method is presented to automatically compute the mid-facial plane on the basis of a surface model of the facial skeleton obtained from CT. The method matches homologous surface areas selected by the user on the left and right facial side using an iterative closest point optimization. The symmetry plane which best approximates this matching transformation is then computed. This new automatic method was evaluated in an experimental study. The study included experienced and inexperienced clinicians defining the symmetry plane by a selection of landmarks. This manual definition was systematically compared with the definition resulting from the new automatic method: Quality of the symmetry planes was evaluated by their ability to match homologous areas of the face. Results show that the new automatic method is reliable and leads to significantly higher accuracy than the manual method when performed by inexperienced clinicians. In addition, the method performs equally well in difficult trauma situations, where key landmarks are unreliable or absent.

Ex vivo assessment of chemotherapy-induced apoptosis and associated molecular changes in patient tumor samples

BACKGROUND: There are inherent conceptual problems in investigating the pharmacodynamics of cancer drugs in vivo. One of the few possible approaches is serial biopsies in patients. However, this type of research is severely limited by methodological and ethical constraints. MATERIALS AND METHODS: A modified 3-dimensional tissue culture technique was used to culture human tumor samples, which had been collected during routine cancer operations. Twenty tumor samples of patients with non-small cell lung cancer (NSCLC) were cultured ex vivo for 120 h and treated with mitomycin C, taxotere and cisplatin. The cytotoxic activity of the anticancer agents was quantified by assessing the metabolic activity of treated tumor cultures and various assays of apoptosis and gene expression were performed. RESULTS: The proliferative activity of the tissue was maintained in culture as assessed by Ki-67 staining. Mitomycin C, cisplatin and taxotere reduced the metabolic activity of the tumor tissue cultures by 51%, 29% and 20%, respectively, at 120 h. The decrease in metabolic activity corresponded to the induction of apoptosis as demonstrated by the typical morphological changes, such as chromatin condensation and nuclear fragmentation. In addition, activated caspase-3 could be verified in apoptotic cells by immunohistochemistry. To verify functional aspects of apoptosis, the induction of chemotherapy-induced cell death was inhibited with the caspase inhibitor z-VAD.fmk. RNA was extracted from the tissue cultures after 120 h of ex vivo drug treatment and was of sufficient quality to allow quantitative PCR. CONCLUSION: The 3-dimensional ex vivo culture technique is a useful method to assess the molecular effects of pharmacological interventions in human cancer samples in vitro. This culture technique could become an important tool for drug development and for the prediction of in vivo drug efficacy.

Activation of T cells by carbamazepine and carbamazepine metabolites

BACKGROUND: T-cell-mediated hypersensitivity is a rare but serious manifestation of drug therapy. OBJECTIVES: To explore the mechanisms of drug presentation to T cells and the possibility that generation of metabolite-specific T cells may provoke cross-sensitization between drugs. METHODS: A lymphocyte transformation test was performed on 13 hypersensitive patients with carbamazepine, oxcarbazepine, and carbamazepine metabolites. Serial dilution experiments were performed to generate drug (metabolite)-specific T-cell clones to explore the structural basis of the T-cell response and mechanisms of antigen presentation. 3-Dimensional energy-minimized structures were generated by using computer modeling. The role of drug metabolism was analyzed with 1-aminobenzotriazole. RESULTS: Lymphocytes and T-cell clones proliferated with carbamazepine, oxcarbazepine, and some (carbamazepine 10,11 epoxide, 10-hydroxy carbamazepine) but not all stable carbamazepine metabolites. Structure activity studies using 29 carbamazepine (metabolite)-specific T-cell clones revealed 4 patterns of drug recognition, which could be explained by generation of preferred 3-dimensional structural conformations. T cells were stimulated by carbamazepine (metabolites) bound directly to MHC in the absence of processing. The activation threshold for T-cell proliferation varied between 5 minutes and 4 hours. 1-Aminobenzotriazole, which inhibits cytochrome P450 activity, did not prevent carbamazepine-related T-cell proliferation. Substitution of the terminal amine residue of carbamazepine with a methyl group diminished T-cell proliferation. CONCLUSION: These data show that carbamazepine and certain stable carbamazepine metabolites stimulate T cells rapidly via a direct interaction with MHC and specific T-cell receptors. CLINICAL IMPLICATIONS: Some patients with a history of carbamazepine hypersensitivity possess T cells that cross-react with oxcarbazepine, providing a rationale for cross-sensitivity between the 2 drugs.