[Update: clinical imaging of cartilage-part 1 : Technical aspects]. / Update: Klinische Knorpelbildgebung ­ Teil 1 : Technische Aspekte.

BACKGROUND: In order to answer clinical therapy-oriented questions, reliable and consistent depiction of articular cartilage across technical platforms is necessary. MATERIALS AND METHODS: Technical standards and developments in cartilage imaging are summarized based on current literature and experience from clinical daily routine. RESULTS: Clinical questions that need to be answered relate to cross-sectional extent, depth, differentiating cartilaginous from bony components of a lesion and to the lesion's location within the compartment. If present, displaced fragments, concomitant meniscal, ligamentous and/or degenerative lesions should be identified. To date, magnetic resonance imaging (MRI) is the workhorse of cartilage imaging and is largely based on moderately T2-weighted and also proton-density (PD)-weighted fat-suppressed turbo-spin-echo sequences. Direct MR- and CT-arthrography are the gold standard to evaluate thin cartilage layers. Recent advances in coil and MR sequence design, increased availability of 3T-MR scanners and more and more sophisticated acceleration techniques allow for better spatial resolution and more robust image contrast at acceptable scan times. DISCUSSION: As abundant as current developments in clinical routine cartilage imaging may be, the radiologist must carefully select the approach best suited to answering the clinical questions.

[Update: Clinical imaging of cartilage-part 2 : Aspects helpul in daily clinical practice]. / Update: Klinische Knorpelbildgebung ­ Teil 2 : In der Klinik hilfreiche Aspekte.

BACKGROUND: Imaging-based analysis of articular cartilage and its defects as well as the radiologist have to live up to the more and more specific clinical questions arising from increasing experience with cartilage-dedicated therapies. MATERIALS AND METHODS: Based on the currently available literature and experience from clinical routine, imaging findings relevant for lesion analysis will be summarized and illustrated by specific pathologies. RESULTS: Local aspects and topographic distribution of bone marrow edema pattern (BMEP), careful analysis of the cartilage surface and of the subchondral plate as well as the patient's clinical and biomechanical context are essential for image analysis. Formal grading is helpful to communicate imaging findings, but in itself is not sufficient for a comprehensive analysis. Assessing the stability of a lesion is important for therapy planning. Imaging is helpful to this end, but can be challenging and requires consideration of the arthroscopic and histologic perspective especially when dealing with juvenile osteochondral lesions. DISCUSSION: In order to maximize the therapeutic and prognostic relevance of findings from cartilage imaging, radiologists need to be sensitive to-often very subtle-imaging clues but at the same time we need to be aware of the limitations of our methods.

Dormancy and activation of human oocytes from primordial and primary follicles: molecular clues to oocyte regulation.

STUDY QUESTION: Do specific transcriptome dynamics in human oocytes from primordial and primary follicles identify novel pathways in oocyte activation? SUMMARY ANSWER: The transcriptomic profiles in oocytes from primordial and primary follicles, respectively, revealed several new canonical pathways as putative mediators of oocyte dormancy and activation. WHAT IS KNOWN ALREADY: Cellular signaling pathways including PI3K/AKT and AKT/mTOR as well as TGF-ß and IGF signaling are known to regulate the primordial-to-primary transition in mammalian follicle development. STUDY DESIGN, SIZE, DURATION: We performed a class comparison study on human oocytes from primordial (n = 436) and primary (n = 182) follicles donated by three women having ovarian tissue cryopreserved before chemotherapy. PARTICIPANTS/MATERIALS, SETTING, METHODS: RNA was extracted from oocytes from primordial and primary follicles isolated by Laser Capture Microdissection, and submitted to the HiSeq Illumina platform. Data mapping, quality control, filtering and expression analysis were performed using Tophat (2.0.4), Cufflinks (2.0.2), BWA (0.6.2) and software R. Modeling of complex biological systems was performed using the IPA® software. Finally, qPCR and immunohistochemistry were employed to explore expression and localization of selected genes and products in human ovarian tissue. MAIN RESULTS AND THE ROLE OF CHANCE: We found 223 and 268 genes down-regulated and up-regulated, respectively, in the oocytes during the human primordial-to-primary follicle transition (P < 0.05 and/or FPKM fold-change >2). IPA® enrichment analysis revealed known pathways ('mTOR Signaling', 'PI3K/AKT Signaling' and 'PTEN Signaling') as well as enriched canonical pathways not previously associated with human ovarian follicle development such as 'ErB Signaling' and 'NGF Signaling' in the down-regulated category and 'Regulation of eIF4 and P70S6K Signaling' and 'HER-2 Signaling in Breast Cancer' in the up-regulated group. Additionally, immunohistochemistry on human ovarian tissue explored the intraovarian localization of VASA, FOXO1 and eIF4E. LARGE SCALE DATA: http://users-birc.au.dk/biopv/published_data/ernst_2017/. LIMITATIONS, REASONS FOR CAUTION: This is a descriptive analysis and no functional studies were performed. The study was based on a limited number of patients and the experimental design could not take into account the natural biological variance in human samples. Therefore, qPCR was used to confirm selected genes alongside immunohistochemical stainings. WIDER IMPLICATIONS OF THE FINDINGS: This study shows, for the first time, a detailed molecular description of global gene transcription activities in oocytes from primordial and primary follicles, respectively. Knowing the global transcription profiles of human oocyte dormancy and activation are important in developing new clinical applications. STUDY FUNDING/COMPETING INTEREST(S): E.H.E. was supported by Health Faculty, Aarhus University and Kong Christian Den Tiendes Fond. K.H. and S.F. were supported by an MRC (UK) project grant MR/M012638/1. K.L.H. was supported by grants from Fonden til Lægevidenskabens Fremme, Kong Christian Den Tiendes Fond. K.L.H. and L.S. were supported by the IDEAS grant from Aarhus University Research Foundation (AUFF). There are no conflicts of interest.

Cyclin-dependent kinase 6 (CDK6) as a potent regulator of the ovarian primordial-to-primary follicle transition.

Introduction: Ovarian follicle development requires tight coordination between several factors to initiate folliculogenesis to generate a mature and fertile egg. Studies have shown that cell cycle factors might contribute to follicle development, hover specific knowledge on individual CDKs and follicle activation has not been investigated. Among cell cycle regulators, CDK6 is a key player through binding to cyclin D resulting DNA synthesis and genome duplication. Interestingly, the CDK6 gene is differentially expressed in oocytes and granulosa cells from human primordial and primary follicles, which suggest a potential role of CDK6 in the primordial-to-primary transition. In this study, we investigated the potential regulatory role of CDK6 in progression of primordial to primary follicle transition using BSJ-03-123 (BSJ), a CDK6-specific degrader. Methods: In mouse ovarian in vitro culture, BSJ reduced the activation of primordial follicles, and reduced follicle development. As a next step, we examined the egg maturation read-out and found that BSJ-treated follicles matured to competent MII eggs with resumption of first meiosis, comparable with the control group. Results: Noteworthy, it appears that inhibition of CDK6 did increase number of apotoptic cells, articular in the granulosa cells, but had no impact on ROS level of cultured ovaries compared to control group, indicating that the cells were not stressed. Oocyte quality thus appeared safe. Discussion: The results of this study indicate that CDK6 plays a role in the primordial-to-primary transition, suggesting that cell cycle regulation is an essential part of ovarian follicle development.

The α2 Na+/K+-ATPase isoform mediates LPS-induced neuroinflammation.

Na+/K+-ATPase is a transmembrane ion pump that is essential for the maintenance of ion gradients and regulation of multiple cellular functions. Na+/K+-ATPase has been associated with nuclear factor kappa B (NFκB) signalling, a signal associated with lipopolysaccharides (LPSs)-induced immune response in connection with activated Toll-like receptor 4 (TLR4) signalling. However, the contribution of Na+/K+-ATPase to regulating inflammatory responses remains elusive. We report that mice haploinsufficient for the astrocyte-enriched α2Na+/K+-ATPase isoform (α2+/G301R mice) have a reduced proinflammatory response to LPS, accompanied by a reduced hypothermic reaction compared to wild type litter mates. Following intraperitoneal injection of LPS, gene expressions of Tnf-α, Il-1ß, and Il-6 was reduced in the hypothalamus and hippocampus from α2+/G301R mice compared to α2+/+ littermates. The α2+/G301R mice experienced increased expression of the gene encoding an antioxidant enzyme, NRF2, in hippocampal astrocytes. Our findings indicate that α2Na+/K+-ATPase haploinsufficiency negatively modulates LPS-induced immune responses, highlighting a rational pharmacological target for reducing LPS-induced inflammation.

Mild versus definite osteoporosis: comparison of bone densitometry techniques using different statistical models.

The purpose of this investigation was to determine the ability of three bone densitometry techniques to discriminate subjects with mild vertebral deformities from those with definite compression fractures. We determined bone mineral density (BMD) in 68 postmenopausal women by quantitative computed tomography (QCT) and dual-photon absorptiometry (DPA) of the spine, as well as single-photon absorptiometry (SPA) of the radius. Forty four individuals were classified as having mild deformities of the spine and 24 were considered to have definite vertebral compressions. Several statistical approaches were used to compare these subgroups and to estimate the relative risk of vertebral fracture. Included among these were percent decrements and zeta-scores, ROC curves, odds ratio estimations, and logistic regression analysis. Individuals with definite vertebral fractures had lower bone mineral density at all sites, but measurement of radial compact bone by SPA failed to reach significance. Using ROC analysis to distinguish mild deformities from true compressions, we found that measurement of spinal trabecular bone by QCT to be the most sensitive discriminator; although measurement of spinal integral bone by DPA also gave satisfactory discrimination, whereas assessment of radial compact bone did not adequately differentiate patients with mild deformities from those with definite compressions. Likewise, we found determination of spinal trabecular bone to be the most robust predictor of relative risk of definite fracture using either odds ratios or logistic regression analysis. Measurement of BMD in the peripheral cortical skeleton offered no predictive power for true vertebral fracture. We concluded that direct assessment of the spine, particularly of the trabecular portion, offered the strongest discrimination and relative risk prediction for definite osteoporotic fractures compared with milder forms of this condition.

Magnetic resonance imaging of the female pelvis. New circularly polarized body array coil versus standard body coil.

RATIONALE AND OBJECTIVES: The authors compare the value of a new circularly polarized body array coil (BAC) system with a standard body coil (BC) for high-resolution magnetic resonance imaging of the female pelvis. METHODS: Twenty patients with cervical cancer were examined with a BC and BAC. Imaging parameters were kept constant (sagittal T2-weighted turbo spin-echo: repetition time = 4000 mseconds; effective echo time = 99 mseconds; 160 x 160 mm field of view; 256 x 256 matrix; 0.63 x 0.63 mm pixel size; 4-mm slice thickness). Images were scored for lesion-to-organ delineation and overall image quality/ artifacts using a scale from 5 to 1 (excellent to poor). Signal-to-noise (S/N) ratios for different tissues (tumor, uterus, vagina, rectum, muscle, and fat) as well as contrast-to-noise (C/N) ratios between tumor and (1) uterus, (2) vagina, and (3) rectum were calculated. Magnetic resonance tumor staging was performed according to the International Federation of Gynecology and Obstetrics (FIGO) classification. RESULTS: Using the BAC, S/N and C/N ratios increased significantly compared with the BC (S/N: 2.7-3.4-fold increase for all organs evaluated, P < 0.001: C/N: tumor versus uterus 2.4-fold, P < 0.01; tumor versus vagina 6.1-fold, P < 0.001; tumor versus rectum 3.1-fold, P < 0.01). This resulted in an improved overall image quality (average ratings: BAC-4.3 points; BC-2.6 points; P < 0.001). Lesion-to-organ delineation (average ratings: BAC 4.3-4.1 points, BC 3.5-2.7 points for all organs evaluated; P < 0.001) was increased noticeably on BAC images. No significant difference was found for staging accuracy. CONCLUSIONS: Circularly polarized BAC provide superior S/N and C/N ratios and improve lesion conspicuity compared with standard BC.

Effects of three different doses of a bolus injection of gadodiamide: assessment of regional cerebral blood volume maps in a blinded reader study.

BACKGROUND AND PURPOSE: Reconstruction of first-pass bolus information to derive regional cerebral blood volume (rCBV) maps is commonly performed in many centers; however, various protocols with different doses of paramagnetic contrast injections have been reported. We evaluated the dose dependency of rCBV maps in a brain tumor population by using three different doses of gadodiamide injection to evaluate their diagnostic accuracy in blinded reader sessions. METHODS: Eighty-three patients with intraaxial brain tumors (72 gliomas) were studied at three centers and randomized to receive a bolus injection of 0.1, 0.2, or 0.3 mmol/kg per body weight of gadodiamide. rCBV maps were generated from T2*-weighted gradient-echo echoplanar sequences at 1.5 T. Data processing was performed according to the indicator dilution theory. RESULTS: The mean contrast-to-noise ratio (CNR) was significantly different between gadodiamide doses of 0.1 and 0.2 mmol/kg (CNR = 8.7 and 15.7) and between 0.1 and 0.3 mmol/kg (CNR = 17.7). No significant difference was found between doses of 0.2 and 0.3 mmol/kg. Sensitivity for the differentiation of benign and malignant brain tumors was 80%, 95%, and 91%, and specificity was 45%, 54%, and 43% by blinded readings at 0.1, 0.2, and 0.3 mmol/ kg, respectively, as compared with histologic findings. Nonblinded readings had a sensitivity of 83%, 100%, and 90% and a specificity of 82%, 100%, and 73% at 0.1, 0.2, and 0.3 mmol/kg, respectively. CONCLUSION: A dose of 0.2 mmol/kg of gadodiamide is recommended for reconstruction of rCBV maps if data are acquired with the T2*-weighted protocol described.

Fluoresceinthiocarbamyl-insulin: a potential analytical tool for the assay of disulfide bond reduction.

We describe the synthesis of fluorescent derivatives of bovine pancreas insulin and its use as substrates of disulfide bond reduction in a spectrofluorometric assay. Amino groups of insulin were chemically modified with fluorescein isothiocyanate and proteins bearing one, two and three fluorescent groups were purified by ion-exchange chromatography. Upon incubation with dithiothreitol, di- and tri-fluoresceinthiocarbamyl-insulin evinced the highest and the lowest enhancement of fluorescence emission, whereas the mono-substituted protein had intermediate enhancement. Using di-fluoresceinthiocarbamyl-insulin, the reliability of this novel feature for the estimation of disulfide bond cleavage was assessed by (i) the separation of two fluorescent bands using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, (ii) the linear response of the fluorescence signal within a range from 0.04 to 1 microM, and (iii) the correlation of the rate of fluorescence enhancement with concentrations of dithiothreitol ranging from 0.1 to 5 mM. Moreover, di-fluoresceinthiocarbamyl-insulin was a sensitive oxidant when the catalytic capacity of thioredoxin and protein disulfide isomerase was analyzed in the presence of dithiothreitol or glutathione, as reductants. On this basis, di-fluoresceinthiocarbamyl-insulin constitutes an analytical tool to test the capacity of biochemical preparations in the reduction of disulfide bonds.

Imaging of the hand: degeneration, impingement and overuse.

Degenerative and overuse diseases as well as impingement syndromes of the hand are illustrated and discussed in this review article. Osteoarthritis of the interphalangeal joints as described by Heberden and Bouchard is a ubiquitous articular disease often associated with synovitis and erosive joint destruction. Osteoarthritis of the trapeziometacarpal joint is classified into four stages for proper indication of operation. Overuse can result in stenosing tenosynovitis around the wrist and in synovitis with or without impingement of the flexor or extensor tendons of the digitis or ruptures of the annular and cruciform pulleys. Although diagnosis of these entities is usually made by history and clinical investigation, ultrasound and MRI can be helpful tools in imaging of these diseases. Scapholunate advanced collapse (SLAC) and scaphoid nonunion advanced collapse (SNAC) are the characteristic degeneration pattern of the wrist and represent the degeneration mechanisms in scapholunate insufficiency and nonunion of the scaphoid. SLAC wrist is a gradual degeneration classified in three stages and found in posttraumatic scapholunate rupture, calcium pyrophosphate dehydrate deposition disease (CPPD), rheumatoid arthritis, neuropathic diseases, trauma, and beta 2-microglobulin associated amyloid deposition. Ulna impaction syndrome is increasingly recognized as a cause of ulnar sided pain and exhibits a characteristic MRI appearance.

Imaging in sports medicine: hand and wrist.

Sports-related injuries of the hand and wrist include lesions of the bones, joints, ligaments, tendons and muscles. In many cases, radiologic imaging procedures are indispensible for the depiction, localization and accurate diagnosis of these lesions. This article reviews the role and potential of current imaging modalities such as conventional radiography, fluoroscopic examinations, arthrography, computed tomography (CT), ultrasound, and magnetic resonance (MR) imaging for the diagnostic work-up of typical osseous and soft tissue injuries in sports medicine.

[Computed tomographic assessment of breathing-induced "pseudo" pneumoperitoneum]. / Computertomographische Beurteilung des beatmungsinduzierten "Pseudo"-Pneumoperitoneums.

The differentiation between a "pseudo" pneumoperitoneum and a pneumoperitoneum due to a perforation may be difficult in unconscious or ventilated patients. The use of CT for differentiating between extraperitoneal and intraperitoneal air is demonstrated by three examples in whom air below the diaphragm was shown by conventional radiographs. CT can prove the extraperitoneal position of an air crescent below the diaphragm in cases of "pseudo" pneumoperitoneum. CT will also show that extraperitoneal air does not rise in the way that true peritoneal air will do when the patient is supine. In this position the viscera therefore do not fall backwards in the presence of a "pseudo" pneumoperitoneum.

[Value of MR for the diagnosis, differential diagnosis and therapy follow-up of Perthes' disease]. / Die Wertigkeit der MR für Diagnostik, Differential-diagnostik und Therapiekontrolle des Morbus Perthes.

59 children were examined by MR, including 31 with Perthes' disease, 7 with subluxating Perthes' disease and 12 with hip pain of unknown origin; the results were compared with conventional radiological findings. MR was superior for the early recognition and for the exact determination of the extent and localisation of juvenile femoral epiphyseal necrosis. It was also of great help in differential diagnosis. It appears to be a suitable method for judging the effect of therapy at an early stage.

[Imaging of epiphyseolysis of the femur head in the magnetic resonance tomogram]. / Die Darstellung der Epiphyseolysis capitis femoris (ECF) im Magnetresonanztomogramm (MRT).

The diagnosis of epiphyseolysis of the femoral head in its early stages is often unclear when using conventional radiography. In order to obtain additional information, we examined seven patients by means of MRT. In all cases the T1-weighted sequences showed widened, ill-defined epiphyseal plates. The epiphyseal displacement was shown accurately by sections of the sagittal plane. T2-weighted sequences showed the presence of an effusion in the hip joints of five patients. In all patients there was increased signal intensity in the metaphysis and in the femoral neck and head. The increased signal intensity appears to be an early sign for the presence of an epiphyseolysis.

[Computed tomographic morphometry of the normal pancreas in adults]. / Computertomographische Morphometrie des normalen Pankreas bei Erwachsenen.

The relationship of the morphology of the normal pancreas, as seen on CT, and age was studied in 200 normal people aged between 19 and 87 years. The A.P. diameter, vertebral body/pancreas ratio, cranio-caudal diameter, contour and structure of the pancreas were analysed. The most marked age-related changed occurred in the vertebral body/pancreas ratio, but all other measurements showed a reduction dependent on age. With increasing age, the contour of the pancreas becomes more lobulated and, at the same time, the structure changes from an homogeneous to an inhomogeneous appearance. These findings correspond with pathological-anatomical observations.

[Imaging of femur head necrosis using MR tomography]. / Die Darstellung der Femurkopfnekrose in der MR-Tomographie.

Magnetic resonance tomography (MR) was used to examine the femoral heads of 20 normals and of 56 patients with diseases of the femoral head, including Perthe's disease (four cases), adult necrosis of the femoral head (39 cases) and pain of unknown cause (13 cases). Femoral head necrosis and Perthe's disease regularly produce reduced signal intensity. The localisation of the areas of necrosis can be determined accurately in the coronary and sagittal plane. In 11 femoral heads, necrosis could be demonstrated unequivocally by MR in the presence of normal radiographic findings. Follow-up of nine patients with negative MR findings and indefinite symptoms confirmed the absence of necrosis.

[MR functional diagnosis of the cervical spine after strain injury]. / MR-Funktionsdiagnostik der Halswirbelsäule nach Schleudertrauma.

50 patients with a history of distortion injury of the cervical spine were examined with static and functional MRI. Functional MRI consisted of different patient's positions from maximal extension to maximal flexion (30 degrees, 0 degrees, 25 degrees, 40 degrees, 50 degrees). T2*-weighted gradient echo sequences were performed in a sagittal view for the different positions. Ligamentous instabilities and disc protrusions were seen only in functional MRI in 17 patients. These findings correlated with the neurological symptoms. Two patients were treated by operative fusion because of these findings.

[MRI in osteochondrosis dissecans]. / MRI bei der Osteochondrosis dissecans.

The osseous manifestations of osteochondrosis dissecans are well demonstrated by conventional and computerised tomography. Beyond that, magnetic resonance imaging (MRI) is effective in evaluating the vitality and loosening of an osseous dissecate. Subchondral cavities and cartilaginous defects are detected with high accuracy. Further, MRI seems to be a useful method in childhood to differentiate a variant irregularity of the osseous articular surface from definite osteochondrosis dissecans.

[Magnetic resonance tomography of the shoulder. Possibilities of over interpretation of normal findings]. / Magnetresonanztomographie (MRT) der Schulter. Möglichkeiten der Uberinterpretation von Normalbefunden.

In order to test the criteria for abnormalities of the shoulder as seen on MR, 30 normal shoulders were examined. The examination included T1, proton and T2-weighted SE sequences and T2*-weighted FE sequences, using transverse, oblique coronary and oblique sagittal planes. In 57% there was increased signal intensity in the tendon of the rotator cuff; this might have been interpreted as a rupture of the cuff or tendinitis. Anatomical examination suggests that the finding is due to a normal layer between the long head of the biceps and the tendon joint complex. The anterior glenoid labrum could not be clearly delineated in 57% and the posterior labrum in 5%. In two cases there was a superior, postero-lateral defect in the head of the humerus. The currently accepted criteria for the MRT diagnosis of shoulder abnormalities need to be critically re-evaluated.

[DSA of the pulmonary vessels during endobronchial laser- and afterloading therapy of malignant bronchial stenoses]. / DSA der Pulmonalgefässe bei endobronchialer Laser- und Afterloadingtherapie maligner Bronchusstenosen.

The findings are reported of the DSA examination of the pulmonary vessels in 16 patients with malignant bronchial stenoses, for whom laser or after-loading therapy was being considered. In these patients an improvement of dyspnoea can be expected only of there is adequate perfusion of the involved lung segment. DSA demonstrated stenoses or occlusions of main pulmonary or lobar arteries in six patients. Ten patients had a normal pulmonary circulation. In most cases the result of the DSA examination was important in determining treatment.