Objective: To examine 11C-methyl methionine (MET) accumulation on positron emission tomographic (PET) imaging of glioblastoma multiforme to determine the distribution of metabolic abnormality ...compared with magnetic resonance imaging (MRI). Methods: Contemporaneous MRI was superimposed on corresponding MET-PET images in 10 patients with newly diagnosed glioblastoma multiforme before treatment. Differences between the extended area of MET accumulation on PET imaging (MET area), the gadolinium (Gd) enhanced area on T1 weighted images (Gd area), and the abnormal high signal intensity area on T2 weighted images (T2-high area) were assessed. Results: The MET area was larger than the Gd area and included the entire Gd area. The discrepancy in volume between the MET and Gd areas became greater with increasing tumour diameter. On average, 58.6% of the MET area was located within the Gd area, 90.1% within 10 mm outside the Gd area, 98.1% within 20 mm, and 99.8% within 30 mm. A newly developed Gd area had emerged in five of the 10 cases up to the time of study. In three of the five cases this was in the MET area even after complete surgical resection of the Gd area on the initial MRI; in the remaining two it originated in the residual Gd area after surgery. In all cases, the T2-high area was larger than the MET area. The MET area extended partly beyond the T2-high area in nine cases, and was completely within it in one. Conclusions: Glioblastoma multiforme cells may extend over the Gd area and more widely with increasing tumour size on Gd-MRI. The T2-high area includes the greater part of the tumour but not its entire area. The methods reported may be useful in planning surgical resection, biopsy, or radiosurgery.
It remains unclear how the immune system affects leukemia development. To clarify the significance of the presence of immune systems in leukemia development, we transferred MLL/ENL leukemia cells ...into immune-competent or immune-deficient mice without any preconditioning including irradiation. The wild-type mice did not develop leukemia, whereas all the Rag2(-/-)γc(-/-) mice lacking both adaptive immune cells and natural killer (NK) cells developed leukemia, indicating that leukemia cells were immunologically rejected. Interestingly, leukemia cells were also rejected in 60% of the Rag2(-/-) mice that lacked adaptive immune cells but possessed NK cells, suggesting that NK cells play a substantial role in the rejection of leukemia. Moreover, engraftment of leukemia cells was enhanced by NK cell depletion in Rag2(-/-) recipients and inhibited by transfer of NK cells into Rag2(-/-)γc(-/-) recipients. Upregulation of NKG2D (NK group 2, member D) ligands in MLL/ENL leukemia cells caused elimination of leukemia cells by NK cells. Finally, we found that leukemia cells resistant to elimination by NK cells had been selected during leukemia development in Rag2(-/-) recipients. These results demonstrate that NK cells can eradicate MLL/ENL leukemia cells in vivo in the absence of adaptive immunity, thus suggesting that NK cells can play a potent role in immunosurveillance against leukemia.
Developmental and seizure outcomes in patients with cryptogenic West syndrome are variable. Our aim was to clarify the relationship between FDG-PET findings in infancy and long-term seizure and ...developmental outcome in cryptogenic West syndrome.
From 1991 to 1999, we prospectively performed FDG-PET from the onset of cryptogenic West syndrome in 27 patients. PET was performed at onset and at 10 months of age. In 2012, we evaluated the educational status, psychomotor development, and seizure outcome in 23 of the 27 patients (13-22 years of age). The correlation between PET findings and outcome was evaluated.
At onset, PET showed hypometabolism in 13 patients (57%). The second PET after the initial treatment revealed cortical hypometabolism in 7 patients (30%). While hypometabolism at onset disappeared on the second PET in 9 patients, it was newly revealed in 3 patients on the second PET. In 2012, seven patients had persistent or recurrent seizures. Eight patients had intellectual impairment. The first PET did not correlate with seizure or developmental outcome. Five of 7 patients (71%) with hypometabolism seen on the second PET had persistent or recurrent seizures, while 14 of 16 (88%) patients with normal findings on the second PET were free of seizures. Five of 7 patients (71%) showing hypometabolism on the second PET had intellectual impairment. Thirteen of 16 (81%) patients with normal findings on the second PET showed normal intelligence. A significant correlation was found between the second PET and long-term seizure (P = .01) or developmental outcome (P = .03).
Cortical hypometabolism is not permanent; it changes with clinical symptoms. Hypometabolism after initial treatment predicts long-term seizures and poor developmental outcome.
The Cherenkov Telescope Array (CTA) consortium aims to build the next-generation ground-based very-high-energy gamma-ray observatory. The array will feature different sizes of telescopes allowing it ...to cover a wide gamma-ray energy band from about 20GeV to above 100TeV. The highest energies, above 5TeV, will be covered by a large number of Small-Sized Telescopes (SSTs) with a field-of-view of around 9°. The Gamma-ray Cherenkov Telescope (GCT), based on Schwarzschild–Couder dual-mirror optics, is one of the three proposed SST designs. The GCT is described in this contribution and the first images of Cherenkov showers obtained using the telescope and its camera are presented. These were obtained in November 2015 in Meudon, 2http://www.cta-observatory.orgFrance.
Neuropsychologic deficits are well-known sequelae of traumatic brain injury. However, the cerebral correlates of these deficits are still unclear. The aim of the present study was to elucidate the ...regions of cerebral dysfunction correlated with such neuropsychologic deficits after traumatic brain injury.
Sets of fluorine-18 fluorodeoxyglucose-positron-emission tomography (FDG-PET) images in the resting state were obtained from 12 patients with neuropsychologic deficits after diffuse axonal injury and from 32 healthy volunteers. The cortical metabolic activity of each subject's PET image sets was extracted using 3D stereotactic surface projection (3D-SSP). A "normal" data base was created using the extracted datasets of the healthy subjects. The patients' datasets were compared with the normal data base by calculating a statistical Z-score on a pixel-by-pixel basis in searches for focal metabolic abnormalities.
Group comparisons revealed hypometabolism in the cingulate gyrus with additional involvement of the lingual gyrus and cuneus. Individual case-by-case analyses disclosed differences in the site and extent of the hypometabolism in the cingulate gyrus of each case. Predominant hypometabolism was found in the anterior cingulate gyrus of 6 patients, the middle cingulate gyrus of 2 patients, and the posterior cingulate gyrus of 4 patients.
Interpretation of FDG-PET using 3D-SSP facilitates the identification of regional hypometabolism in the cerebral cortex of patients after diffuse axonal injury. Dysfunction of the cingulate gyrus, lingual gyrus, and cuneus may play a crucial role in neuropsychologic deficits after traumatic brain injury.
The transcription factor, interferon regulatory Factor 3 (IRF-3) plays a critical role in the activation of an antiviral innate immune response. However the transcriptional activity of IRF-3 is ...tightly regulated by a proteosome mediated degradation. We describe here a novel mechanism by which the activity of IRF-3 is stabilized in infected cells. We have shown that both interferon treatment and NDV infection profoundly increase conjugation of interferon induced ubiquitin- like protein ISG15 to cellular proteins. ISGylated IRF-3 could be detected both in interferon treated and virus-infected cells. ISG15, subverts the ubiquitin mediated degradation of IRF-3 in NDV infected 2fTGH cells and enhances the NDV mediated transactivation of interferonbeta promoter and the translocation of activated IRF-3 to the nucleus. The relative levels of IRF-3 were significantly lower in NDV infected ISG15 null MEF, than in wt MEF. While ISG15 null MEF were more permissive to VSV replication their sensitivity to the antiviral effect of interferon was not modulated. These results reveal that virus mediated subversion of the antiviral response by proteolysis of IRF-3 is counteracted by induction of ISG15 expression and that ISGylation provides a feedback mechanism, which enhances the host innate antiviral response via IRF-3 stabilization.
Light collection efficiency from BGO crystal scintillators of various sizes and shapes was measured by reading them using 1×1cm2 avalanche photo diodes. When the crystals have simple geometry, the ...light collection efficiency was found to depend on their size, shape and the read-out position through a rather well-defined empirical scaling relation. The light collection efficiency of tapered crystals was seen to depend on both the position of γ-ray irradiation, and the read-out position of the avalanche photo diodes. Using optical Monte-Carlo simulations, the relation was reproduced assuming plausible proper parameters for surface conditions and the attenuation length. This results were reproduced with a reasonable accuracy by optical Monte-Carlo simulations. Simple physical explanations are given to these geometrical effects.
•We studied light output of different shapes and size BGO crystals with an APD.•With a Monte-Carlo simulation, we successfully reproduced measured light outputs of BGO.•We derived a scaling law of a rectangle crystal volume and surface area APD attached.•We measured a dependence of the light output on a position with non-rectangle crystal.