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Contains fulltext : 292741.pdf (Publisher’s version ) (Open Access) The post-treatment imaging surveillance of gliomas is challenged by distinguishing tumor progression (TP) from treatment-related abnormalities (TRA). Sophisticated imaging techniques, such as perfusion-weighted magnetic resonance imaging (MRI PWI) and positron-emission tomography (PET) with a variety of radiotracers, have been suggested as being more reliable than standard imaging for distinguishing TP from TRA. However, it remains unclear if any technique holds diagnostic superiority. This meta-analysis provides a head-to-head comparison of the diagnostic accuracy of the aforementioned imaging techniques. Systematic literature searches on the use of PWI and PET imaging techniques were carried out in PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and the reference lists of relevant papers. After the extraction of data on imaging technique specifications and diagnostic accuracy, a meta-analysis was carried out. The quality of the included papers was assessed using the QUADAS-2 checklist. Nineteen articles, totaling 697 treated patients with glioma (431 males; mean age ± standard deviation 50.5 ± 5.1 years) were included. The investigated PWI techniques included dynamic susceptibility contrast (DSC), dynamic contrast enhancement (DCE) and arterial spin labeling (ASL). The PET-tracers studied concerned [S-methyl-(11)C]methionine, 2-deoxy-2-[(18)F]fluoro-D-glucose ([(18)F]FDG), O-(2-[(18)F]fluoroethyl)-L-tyrosine ([(18)F]FET) and 6-[(18)F]-fluoro-3,4-dihydroxy-L-phenylalanine ([(18)F]FDOPA). The meta-analysis of all data showed no diagnostic superior imaging technique. The included literature showed a low risk of bias. As no technique was found to be diagnostically superior, the local level of expertise is hypothesized to be the most important factor for diagnostically accurate results in post-treatment glioma patients regarding the distinction of TRA from TP.

SummaryA significant number of COVID-19 patients develop ‘long COVID’, a condition defined by long-lasting debilitating, often neurological, symptoms. The pathophysiology of long COVID is unknown. Here we present in-vivo evidence of widespread neuroinflammation in long COVID, using a quantitative assessment, [18F]DPA-714 PET, in two long COVID patients. We reanalyzed historical data from three matched healthy control subjects, for comparison purposes. Both patients with long COVID had widespread increases in [18F]DPA-714 binding throughout the brain. Quantitative measures of binding (BPND values) were increased on average by 121% and 76%, respectively. This implicates profound neuroinflammation in the pathophysiology of long COVID.

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.

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.

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.

Comparing wrist shapes of different individuals requires alignment of these wrists into the same pose. Unconstrained registration of the carpal bones results in anatomically nonfeasible wrists. In this paper, we propose to constrain the registration using the shapes of adjacent bones, by keeping the width of the gap between adjacent bones constant. The registration is formulated as an optimization involving two terms. One term aligns the wrist bones by minimizing the distances between corresponding bone surfaces. The second term constrains the registration by minimizing the distances between adjacent sliding surfaces. The registration is based on the Iterative Closest Point algorithm. All bones are registered concurrently so that no bias is introduced towards any of the bones. The proposed registration method delivers anatomically correct configurations of the bones. The registration errors are in the order of the voxel size of the acquired CT data (0.3 times 0.3 times 0.3 mm3). The standard deviation in the widths of gaps between adjacent bones is in the order of 10% with an insignificant bias. This is a large improvement over the standard deviations of 30%-80% encountered in unconstrained registration. The value of this method is its capability of accurately registering joints in varying poses resulting in physiological joint configurations.

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

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 × 105 and 4 × 104 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 mm3 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. Electronic supplementary material The online version of this article (doi:10.1007/s11307-014-0799-z) contains supplementary material, which is available to authorized users.

Minimally invasive surgeries are approaching 50% of all interventional procedures in the US, yet there is a lack of objective tools to assist surgeons in this limited sensing environment. In this preliminary work, we present a novel proof of concept implementation of Single Snapshot of Optical Properties (SSOP) imaging through a rigid endoscope. In this embodiment, a stereo rigid endoscope is used with one channel to project spatially modulated illumination and the second channel to image the diffuse reflectance onto a CCD sensor. Optical property maps are then obtained for various tissue simulating phantoms and validated against standard wide-field spatial frequency domain imaging (SFDI). The implementation of endoscopic SSOP creates potential for practical use of endoscopic tissue constituent quantification. The results show good agreement (within 5%) for endoscopic SSOP versus wide-field SFDI. However, endoscopic SSOP acquisition allows for video-rate imaging, limited only by the exposure time of image capture. These results show promise for an objective endoscopic tissue viability assessment tool being achievable in a clinical setting.

To provide plasma-physics scientists with worldwide access to historical and current measurement data from the Textor-94 Tokamak experiment, we developed a new architecture: the "WebUmbrella." It uses HTTP to transfer data in (X)HTML, plain text, or other MIME-type documents. We provide a single point of access to our servers via HTTP redirection. Server implementations for several data stores are already present, and the first user tests are positive. In particular, we present one server implementation that provides access to already existing common object request broker architecture (CORBA) servers. It uses the Apache Web server and the Tomcat Servlets engine, and consists of Java Servlets that convert HTTP requests into CORBA requests for the existing interface. These developments are the aftermath of an earlier experience with CORBA interface definition language (IDL) interfaces between user clients and several data servers, which provide access to-the different data stores. The interfaces were developed in a telematics application program project, "Dynacore." After the evaluation of this demonstrator, we designed a new system to improve the service. Because of the positive experience, we inherited the data representation, the data-browsing features, and the single access point for clients to several data stores. We tried to eliminate the obligatory use of CORBA, as its added value did not weigh up against,the problems we faced using it: CORBA is difficult to understand for scientists inexperienced in object-oriented design and difficult to access with simple analysis tools like IDL or MATLAB. We also did not find a suitable CORBA implementation for Virtual Address eXtension/Virtual Memory System (VAX/VMS) with C/Fortran bindings. Finally, WebUmbrella's transport protocol, contrary to CORBA's, does not suffer from firewall and access problems.

BackgroundThe 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.MethodsIn 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.FindingsIn 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.InterpretationThe 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.

Fluorescence loss in photobleaching (FLIP) is a method to study compartment connectivity in living cells. A FLIP sequence is obtained by alternatively bleaching a spot in a cell and acquiring an image of the complete cell. Connectivity is estimated by comparing fluorescence signal attenuation in different cell parts. The measurements of the fluorescence attenuation are hampered by the low signal to noise ratio of the FLIP sequences, by sudden sample shifts and by sample drift. This paper describes a method that estimates the attenuation by modeling photobleaching as exponentially decaying signals. Sudden motion artifacts are minimized by registering the frames of a FLIP sequence to target frames based on the estimated model and by removing frames that contain deformations. Linear motion (sample drift) is reduced by minimizing the entropy of the estimated attenuation coefficients. Experiments on 16 in vivo FLIP sequences of muscle cells in Drosophila show that the proposed method results in fluorescence attenuations similar to the manually identified gold standard, but with standard deviations of approximately 50 times smaller. As a result of this higher precision, cell compartment edges and details such as cell nuclei become clearly discernible. The main value of this method is that it uses a model of the bleaching process to correct motion and that the model based fluorescence intensity and attenuation estimates can be interpreted easily. The proposed method is fully automatic, and runs in approximately one minute per sequence, making it suitable for unsupervised batch processing of large data series.

Direct imaging of ligament damage in the wrist remains a challenge. Still, such damage can be assessed indirectly through the analysis of changes in wrist pose and motion pattern. For this purpose we built a statistical reference model that describes healthy motion patterns. We show that such a model can also be used to detect and quantify pathologies. A model that only describes the global translations and rotations of the carpal bones is insufficiently accurate due to size and shape variations of the bones. We present a local statistical motion model that minimizes the influence of size and shape differences by analyzing the coordinate differences of pairs of points on adjacent bone surfaces. These differences are determined in a set of 14 healthy example wrists imaged in a range of poses by means of 4D-RX imaging. The distribution of the differences as a function of the pose form the local statistical-motion model (LSMM). Translations of 2 mm and rotations of 20 degrees with respect to the healthy example wrists are detected as outliers in the point pair distributions. An evaluation involving wrists with a damaged ligament between scaphoid and lunate shows that not only joint space widenings can be detected, but also shifts of congruent bone surfaces. The LSMM is also used to perform a virtual reconstruction of the most likely healthy wrist after a simulated perturbation of bones. The reconstruction precision is shown to be about 1 mm. Therefore, the presented 4D statistical model of wrist bone movement may become a valuable clinical tool for diagnosis and surgical planning

Udgivelsesdato: 2010-Apr-28 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 degrees extension, and 40 degrees 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 degrees and a small (less than 1 mm) radial, distal, and dorsal translation of the distal pole in 30 degrees 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.

Polymorphisms in the dopamine transporter (DAT) gene SLC6A3 are associated with human striatal DAT expression, but the exact effects on DAT expression are not clear. A variable number of tandem repeats (VNTR) in the 3' untranslated region of the DAT gene was previously investigated in relation to striatal DAT availability, but the results were inconclusive. Other polymorphisms in the DAT gene were not extensively studied. Therefore, we investigated whether polymorphisms in both 3' and 5' ends of the DAT gene show association with in vivo striatal DAT expression. METHODS: The subjects were an ethnically homogeneous group of 79 healthy young adults. Striatal DAT availability was measured with (123)I-(2-beta-carbomethoxy-3-beta(4-iodophenyl)-tropane) ((123)I-beta-CIT) SPECT. The 40-base-pair VNTR in the 3' untranslated region of the DAT gene and the 2 single nucleotide polymorphisms (SNPs) rs2652511 and rs2937639 in the 5' end of the DAT gene were genotyped. Multiple-regression analysis was performed for each of the 3 polymorphisms. Analysis of the combination of the polymorphisms (haplotype analysis) was conducted for the triad rs2652511-rs2937639-VNTR. RESULTS: For the VNTR, the 9-repeat (9R) allele was associated with significantly higher striatal DAT expression than was the 10-repeat (10R) allele (P = 0.002). Subanalysis suggested a dominant effect for the 9R allele. Neither SNP rs2652511 nor SNP rs2937639 was associated with striatal DAT availability. The haplotype T-A-9R (rs2652511-rs2937639-VNTR) was significantly more associated with higher striatal DAT expression than were the other haplotypes (P = 0.009). CONCLUSION: The DAT VNTR 9R carriers have higher striatal DAT availability than do 10R homozygotes. This finding replicates former studies that included healthy subjects and also used (123)I-beta-CIT SPECT. Our haplotype analysis identified a subgroup of 9R carriers, the T-A-9R, which appears to be mainly responsible for the association with higher striatal DAT availability. Thus, a combination of polymorphisms in both the 3' and the 5' ends of the DAT gene is associated with in vivo striatal DAT expression. This finding in healthy subjects may contribute to research on DAT availability and genotype in neuropsychiatric disorders

Current diagnosis of wrist joint problems is hampered by poor understanding of wrist joint functioning. To gain insight into the relationship between function and anatomy we aim at building a statistical shape model of the wrist. As a basis for the statistical model we intend to use CT scans of different individuals that are mutually registered to a common pose. Unconstrained registration of individual bones does not lead to an anatomically feasible arrangement of the carpal bones. We propose to use a constrained 3D registration, where bone movements are based on bone geometry and joint kinematics. Constrained co-registration of wrists from different individuals in different postures demonstrates that our method finds anatomically feasible wrists in the same posture that are therefore a sound basis for a statistical shape model