Chronic inflammation is accompanied by impaired T-cell immunity. In the mouse, myeloid cell-associated arginase accounts for the suppression of immune reactivity in various models of tumor growth and chronic infections. Here we show that arginase I is liberated from human granulocytes, and very high activities accumulate extracellularly during purulent inflammatory reactions. Human granulocyte arginase induces a profound suppression of T-cell proliferation and cytokine synthesis. This T-cell phenotype is due to arginase-mediated depletion of arginine in the T-cell environment, which leads to CD3 chain down-regulation but does not alter T-cell viability. Our study therefore demonstrates that human granulocytes possess a previously unanticipated immunosuppressive effector function. Human granulocyte arginase is a promising pharmacologic target to reverse unwanted immunosuppression.
Multimodality imaging and, more specifically, the combination of PET and CT has matured into an important diagnostic tool. During the same period, concepts for PET scanners integrated into an MR tomograph have emerged. The excellent soft-tissue contrast of MRI and the multifunctional imaging options it offers, such as spectroscopy, functional MRI, and arterial spin labeling, complement the molecular information of PET. The development of a fully integrated PET/MRI system is technologically challenging. It requires not only significant modifications of the PET detector to make it compact and insensitive to magnetic fields but also a major redesign of the MRI hardware.Key Words: clinical multimodality imaging; PET; CT; PET/CT; arterial spin labeling (ASL); fMRI; spectroscopy; magnetic resonance tomograph (MRT); PET/MRI; positron emission tomography; MR/PET J Nucl Med 2010; 51: 333-336 DOI: 10.2967/jnumed.109.061853 Over the last 20 years, PET and MRI systems have evolved slowly but steadily. The photomultiplier-based PET detectors have remained more or less unchanged, ensuring stable operation and good signal performance despite bulk and high sensitivity to even the smallest magnetic fields. Improvements in PET technology were achieved with faster and low-noise electronics, faster and brighter scintillation crystals, optimized light-sharing schemes for the scintillation crystal arrangements, and smaller crystals (1). These adaptations led to PET scanners with whole-body scan times as short as 10 min, yielding-together with improved reconstructions, attenuation-and scatter-correction algorithms-low-noise PET images. Advances paved the way to implementing the idea of time-of-flight PET in clinical scanners (2). Without a doubt, the most important step toward the establishment of PET as a clinically viable tool was the introduction of combined PET/ CT in 1998 by David Townsend and Ronald Nutt (3-5). Nevertheless, many physicians of that time remained skeptical about the advantages of this dual-modality imaging system over stand-alone PET and CT.Clinical MRI evolved toward higher fields, faster imaging sequences, and whole-body imaging capabilities. Especially for brain imaging, 3-T MRI is now the standard. Novel coil concepts combined with parallel acquisition techniques helped shorten examination times while maintaining high imaging quality (6). PET/MRI: TECHNICAL EVOLUTIONThe idea to combine PET and MRI arose as early as the mid 1990s, even before PET/CT was introduced. Simon Cherry and Paul Marsden saw the need for PET/MRI in small-animal imaging studies to add anatomic landmarks with high softtissue contrast to the molecular information delivered by PET (7). Preclinical PET/MRI work was followed by immediate commercial interest in combining PET and MRI, probably driven by the limited sensitivity of MRI to trace biomarkers or to reveal metabolites.The PET/MRI combination requires 3 risky technologic steps that modify state-of-the-art PET and MRI. First, the photomultiplier technology must be replaced with magn...
Simultaneous PET and MRI using new hybrid PET/MRI systems promises optimal spatial and temporal coregistration of structural, functional, and molecular image data. In a pilot study of 10 patients with intracranial masses, the feasibility of tumor assessment using a PET/MRI system comprising lutetium oxyorthosilicate scintillators coupled to avalanche photodiodes was evaluated, and quantification accuracy was compared with conventional PET/CT datasets. Methods: All measurements were performed with a hybrid PET/MRI scanner consisting of a conventional 3-T MRI scanner in combination with an inserted MRI-compatible PET system. Attenuation correction of PET/MR images was computed from MRI datasets. Diagnoses at the time of referral were low-grade astrocytoma (n 5 2), suspicion of low-grade astrocytoma (n 5 1), anaplastic astrocytoma (World Health Organization grade III; n 5 1), glioblastoma (n 5 2), atypical neurocytoma (n 5 1), and meningioma (n 5 3). In the glial tumors, 11 C-methionine was used for PET; in the meningiomas, 68 Ga-DOTATOC was administered. Tumor-togray matter and tumor-to-white matter ratios were calculated for gliomas, and tracer uptake of meningiomas was referenced to nasal mucosa. PET/MRI was performed directly after clinically indicated PET/CT examination. Results: In all patients, the PET datasets showed similar diagnostic image quality on the hybrid PET/MRI and the PET/CT studies; however, slight streak artifacts were visible in coronal and sagittal sections when using the higher intrinsic resolution of the PET/MRI insert. Prefiltering of images with a 4-mm gaussian filter at a resolution comparable to that of the PET/CT system virtually eliminated these artifacts. Although acquisition of the PET/MR images started at 30-60 min after PET/CT (20.4-min half-life of 11 C) acquisition, the signal-to-noise ratio was good enough, thus underlining the high sensitivity of the PET insert, compared with whole-body PET systems. The computed tumor-to-reference tissue ratios exhibited an excellent accordance between the PET/MRI and PET/CT systems, with a Pearson correlation coefficient of 0.98. Mean paired relative error was 7.9% 6 12.2%. No significant artifacts or distortions were detected in the simultaneously acquired MR images using the PET/MRI scanner. Conclusion: Structural, functional, and molecular imaging in patients with brain tumors is feasible with diagnostic imaging quality using simultaneous hybrid PET/MR image acquisition.
• Combination of PET and MRI is a new emerging imaging technology. • Evaluated brain PET/MRI enables uncompromised imaging performance. • PET/MRI aims to provide multiparametric imaging allowing acquisition of morphology and metabolism.
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