Image quality and cancer visibility of T2-weighted magnetic resonance imaging of the prostate at 7 Tesla.

OBJECTIVES: To assess the image quality of T2-weighted (T2w) magnetic resonance imaging of the prostate and the visibility of prostate cancer at 7 Tesla (T). MATERIALS & METHODS: Seventeen prostate cancer patients underwent T2w imaging at 7T with only an external transmit/receive array coil. Three radiologists independently scored images for image quality, visibility of anatomical structures, and presence of artefacts. Krippendorff's alpha and weighted kappa statistics were used to assess inter-observer agreement. Visibility of prostate cancer lesions was assessed by directly linking the T2w images to the confirmed location of prostate cancer on histopathology. RESULTS: T2w imaging at 7T was achievable with 'satisfactory' (3/5) to 'good' (4/5) quality. Visibility of anatomical structures was predominantly scored as 'satisfactory' (3/5) and 'good' (4/5). If artefacts were present, they were mostly motion artefacts and, to a lesser extent, aliasing artefacts and noise. Krippendorff's analysis revealed an α = 0.44 between three readers for the overall image quality scores. Clinically significant cancer lesions in both peripheral zone and transition zone were visible at 7T. CONCLUSION: T2w imaging with satisfactory to good quality can be routinely acquired, and cancer lesions were visible in patients with prostate cancer at 7T using only an external transmit/receive body array coil. KEY POINTS: • Satisfactory to good T2-weighted image quality of the prostate is achievable at 7T. • Periprostatic lipids appear hypo-intense compared to healthy peripheral zone tissue at 7T. • Prostate cancer is visible on T2-weighted MRI at 7T.

[Diffusion-weighted MRI of the prostate]. / Diffusionsgewichtete MRT der Prostata.

Diffusion-weighted magnetic resonance imaging (DWI) can complement MRI of the prostate in the detection and localization of prostate cancer, particularly after previous negative biopsy. A total of 13 original reports and 2 reviews published in 2010 demonstrate that prostate cancer can be detected by DWI due to its increased cell density and decreased diffusiveness, either qualitatively in DWI images or quantitatively by means of the apparent diffusion coefficient (ADC). In the prostate, the ADC is influenced by the strength of diffusion weighting, localization (peripheral or transitional zone), presence of prostatitis or hemorrhage and density and differentiation of prostate cancer cells. Mean differences between healthy tissue of the peripheral zone and prostate cancer appear to be smaller for ADC than for the (choline + creatine)/citrate ratio in MR spectroscopy. Test quality parameters vary greatly between different studies but appear to be slightly better for combined MRI and DWI than for MRI of the prostate alone. Clinical validation of DWI of the prostate requires both increased technical conformity and increased numbers of patients in clinical studies.

Tissue culture studies in Hodgkin's disease: Morphologic, cytogenetic, cell surface, and enzymatic properties of cultures derived from splenic tumors.

Monolayer and suspension cell cultures prepared from Hodgkin's disease tumors in the spleen were examined microscopically and by cytogenetics, tested for lymphocyte and monocyte cell surface properties, and assayed for enzymes by histochemical and spectrophotometric techniques. Hodgkin's disease monolayer cultures were composed of rapidly proliferating round and polygonal cells that were capable of propagation in vitro for an indefinite period of time. Abnormal aneuploid chromosomes were found in short-term Hodgkin's disease monolayers that had been passaged 16-20 times, and in established cell lines carried in culture longer than 3 yr and passaged more than 200 times. Cells fromHodgkin's disease monolayers contained lysozyme (muramidase), fluoride-resistant alpha naphthol acetate esterase, acid and alkaline phosphatase, and chymotrypsin-like activity. The monolayers did not exhibit specific cell surface markers or phagocytosis. Suspension cultures derived from Hodgkin's disease monolayers were composed of cells with aneuploid karyotypes and similar enzymes. The Hodgkin's disease suspension culture cells had surface receptors for complement and IgGFc, lacked surface or cytoplasmic immunoglobulin, and did not form Erosettes, react with an antithymocyte serum, nor exhibit phagocytosis. Normal monolayer culture cells, derived from adult spleen and human fetal spleen and thymus, were composed of spindle cells with a diploid number of chromosomes that could be carried for only a finite period of time in vitro. Normal cultured cells contained similar esterases and phosphatases, but were devoid of lysozyme and chymotrypsin-like activity. The morphologic, cytogenetic, cell surface, and enzymatic findings indicate that our Hodgkin's disease monolayer and suspension cultures are composed of cells with many properties suggesting an origin from monocytes (macrophages) rather than lymphocytes or fibroblasts. The presence of aneuploid karyotypes is consistent with a neoplastic origin and derivation from a malignant cell of Hodgkin's disease.

Chromatographic and electrophoretic analysis of an antigen in Hodgkin's disease tissue cultures.

An antigen in tissue cultures derived from Hodgkin's disease tumors was investigated by polyacrylamide gel electrophoresis, column chromatography, and isotopic antibody techniques. Fourteen long-term, serially passaged monolayer cultures prepared from tumor nodules of Hodgkin's disease in the spleen were studied; 11 monolayers derived from normal adult spleen and human fetal spleen and thymus were used as controls. Cell-free medium from Hodgkin's disease and normal cultures were centrifuged, and the pellet fractions were sedimented in a discontinuous sucrose gradient, solubilized with dodium dodecyl sulfate, and labeled with radioiodine. Gel filtration and electrophoresis revealed a component in samples prepared from medium of Hodgkin's disease cultures that was not observed in medium from normal cultures. An antiserum made in rabbits against this component reacted by radioiodine-labeled antibody assay with an antigen on the surface on cells from Hodgkin's disease cultures that was present in very small amounts, or in a cryptic state, on normal cultured cells. This antigen, intimately associated with propagation of cells obtained from the tumor in vitro, was not demonstrable in noncultured Hodgkin's disease tissue...

An in vivo effect of the metabolites L-alanine and glycyl-L-leucine on the properties of lysyl-tRNA synthetase from Escherichia coli K-12. I. Influence on subunit composition and molecular weight distribution.

Lysyl-tRNA synthetase was purified to 70-90% of homogeneity from Escherichia coli K-12. The enzyme was purified from wild-type cells grown in minimal medium, or minimal medium containing either 20 mM L-alanine or 3 mM glycly-L-leucine. The synthetase was similarly purified from a mutant strain grown in minimal medium plus 20 mM L-alanine. Results based on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, gel filtration, and trypsin inactivation studies indicate (A) that the presence of L-alanine of glycyl-L-leucine in the culture medium alters the properties of the wild-type enzyme; (B) that the alteration of the synthetase by l-alanine and glycyl-L-leucine is different; and (c) that the molecular weight of lysyl-tRNA synthetase is at least 135000--140000. The results suggest that most likely the metabolites modify the structure of lysyl-tRNA synthetase, but the possibility that the metabolites induce the synthesis of a new lysyl-tRNA synthetase cannot be completely eliminated.

Diadenosine 5',5'''-P1,P4-tetraphosphate, a potential antithrombotic agent.

Diadenosine tetraphosphate (AP4A), a competitive inhibitor of ADP-induced platelet aggregation, was tested as an antithrombotic agent in a rabbit intracarotid thrombosis model previously shown to be sensitive to antiplatelet agents. Eighty-four percent of control rabbits formed clots. The infusion of AP4A at a dose of 50 mg/kg over 2 hours reduced the incidence of thrombosis to 56% (p less than 0.05). Blood AP4A increased 125-fold at the end of infusion, but was completely cleared within 10 minutes. Plasma ATP showed bimodal early and late increases. Platelets recovered from AP4A-treated rabbits exhibited a pattern of reduced reactivity to ADP, but not to collagen, similar to platelets exposed to AP4A in vitro. This study shows that AP4A may be a potentially useful antithrombotic agent.

Diagnosis of storage pool deficiency by determination of diadenosine 5', 5'''-P1,P4-tetraphosphate in whole blood.

Platelets from cat and cattle with Chediak-Higashi disease were found completely devoid of Ap4A as measured by high performance liquid chromatography. Using a very sensitive firefly biolumnescence method 6% of the normal content of Ap4A was, however, found in platelets from sick animals. A content of Ap A of 1.90 +/- 0.11 X 10 M (means +/- SEM, n = 10) was found in whole normal human blood as measured by firefly bioluminescense method in trichloroacetic acid extracts of the blood samples. This concentration corresponds to the contribution from the platelets, thus the contribution of Ap4A from erythrocytes and the "buffy-coat" is negligible. Using the same method an Ap4A contents in platelets of 0.063 and 0.021 nmol/mg of protein compared to the normal content of 0.42 nmol/mg of protein (1) was found in two patients with severe myeloproliferative disorder calculated in this way on basis of platelet counts and on the assumption that 10(11) platelets contain 189 mg of protein (2). Comparison of these figures with parallel HPLC analyses on acid extracts of platelets isolated from the same patient were in agreement. The storage pool deficiency of adenine nucleotides in this disease found by others on basis of release experiments (3) can thus be diagnosed by rapid and simple measurements of Ap4A in whole blood using the advantage of Ap4A being a specific components stored in dense granules.

History of antisense oligonucleotides.

Biological science is a rapidly flowing experimental stream, at times encountering a dam that impedes further progress. At such a pomt, a single crack may induce a major breakthrough Discovery of the double helical structure of DNA in 1953 (1) caused such an event, with flooding of new information into the area now known as molecular biology.

A new contrast in MR mammography by means of chemical exchange saturation transfer (CEST) imaging at 3 Tesla: preliminary results.

PURPOSE: To evaluate the feasibility to detect and delineate malignant breast lesions in human patients by chemical exchange saturation transfer (CEST) as an MR imaging technique without the need for contrast agent administration. MATERIALS AND METHODS: Six female patients referred for pre-surgical staging due to histologically confirmed breast cancer were examined with MR at 3 T. The routine breast protocol included T (2w), STIR, T (1w)-DCE and contrast-enhanced T (1w) imaging with SPAIR fat suppression. For CEST imaging, a 3D RF-spoiled gradient echo (GRE) sequence with an optimized saturation pulse train was applied. To assess the diagnostic value of the technique, CEST effects observed between frequency offsets of 1.2 to 1.8 ppm from the bulk water resonance were compared to pharmacokinetic parameter maps (k (ep)) obtained by DCE-MRI. RESULTS: In 3 of 6 patients, regions with high CEST signal intensity correlated well with tumor areas as determined by DCE-MRI. Analysis of signal intensities from ROIs in tumor, fibroglandular, adipose, and muscle tissue revealed significantly higher CEST values in tumor tissue compared to fibroglandular tissue. The detection of lesions was equally well possible with DCE-MRI and CEST-MRI. In the three other patients, the tumor regions could not be delineated based on the CEST image due to artifacts, which were most likely caused by a high content of fat tissue within the ROIs. CONCLUSION: The results of this initial feasibility study indicate a significant potential of CEST-MRI to discriminate cancer from fibroglandular tissue in the human breast by a CEST contrast generated by endogenous solute molecules.