Attenuation correction in cardiac PET/CT with three different CT protocols: a comparison with conventional PET

Purpose CT-based attenuation correction may influence cardiac PET owing to its higher susceptibility to misalignment compared with conventional ⁶⁸Ge transmission scans. The aims of this study were to evaluate whether CT attenuation correction leads to changes in tracer distribution compared with conventional cardiac PET and to determine a suitable CT protocol. Methods A total of 27 patients underwent PET/CT and subsequently a PET scan. Twenty patients received a low-dose CT (LDCT group; 120 kV, 26 mA, 8-s scan time), seven patients a slow CT (SCT group; 120 kV, 99 mA, 46-s scan time) and ten patients an ultra-low-dose CT (ULDCT group; 80 kV, 13 mA, 5-s scan time) as the transmission scan in PET/CT. Polar maps were divided into 17 segments and regression analysis was computed in every scan pair (CT attenuation corrected–⁶⁸Ge attenuation corrected). Correlation coefficient (r), the slope (s) and the offset (os) of the regression line were determined. Visual assessment of misalignment between the transmission and emission data was performed. The effective dose of the different transmission scans was calculated. Results Overall, there was a moderate correlation between the mean values measured in all segments on PET/CT and on PET when using LDCT (r=0.78, p<0.0001), SCT (r=0.79, p<0.0001) and ULDCT (r=0.82, p<0.0001). No differences were observed when comparing the scores assigned in the visual misalignment assessment in the three groups (p=0.12). The differences between the results from the regression analysis observed in the respective groups were not statistically significant (Kruskal-Wallis p=0.11 for r, p=0.67 for s and p=0.27 for os). The effective dose was lowest for the ULDCT. Conclusion Our study shows that CT-based attenuation correction is feasible for cardiac PET imaging. The results indicate that ultra-low-dose CT is the preferable choice for transmission scanning.     

The Evolving Systemic and Local Biomarker Milieu at Different Stages of Disease Progression in Rat Adjuvant-Induced Arthritis

Introduction  Rats with adjuvant-induced arthritis (AIA) were necropsied on 14 occasions during preclinical, acute clinical and chronic clinical stages of AIA progression to characterize local (joint protein extracts) and systemic (serum) levels of mediators regulating inflammation and bone erosion in conjunction with lymphoid tissue-specific leukocyte kinetics. Results  Systemic increases in alpha1 acid glycoprotein, tumor necrosis factor-α (TNFα), interleukin (IL)-17, transforming growth factor beta (TGFβ), and chemokine (C–C motif) ligand 2 (CCL2) together with local IL-1α/β and TGFβ enrichment and local lymphoid hyperplasia preceded the onset of clinical disease and joint damage. Systemic upregulation of TNFα, IL-6, IL-17, TGFβ, IL-18, CCL2, receptor activator of nuclear factor-κβ ligand (RANKL), and prostaglandin E₂ during acute and/or chronic AIA coincided with systemic leukocytosis and CD4+ T cell increase in blood and spleen. In contrast, progression of joint erosions during clinical AIA was associated with intra-articular increases in IL-1α/β, IL-6, RANKL, IL-17, TGFβ, CCL2, and KC/GRO and also a dramatic decline in osteoprotegerin. Conclusion  These data indicate that systemic and local events in inflammatory arthritis are discrete processes, driven by multiple cellular and humoral mediators with distinct kinetic profiles.     

Effective activation alleviates the replication block of CCR5-tropic HIV-1 in chimpanzee CD4+ lymphocytes

Human immunodeficiency virus type 1 (HIV-1) originated in chimpanzees; yet, several previous studies have shown that primary HIV-1 isolates replicate poorly in chimpanzee CD4+ T lymphocytes in vitro and in vivo. The reasons for this apparent restriction are not understood. Here, we describe a new activation protocol that led to a reproducible expansion and activation of chimpanzee CD4+ T lymphocytes in vitro. Using this protocol, we uncovered species-specific differences in the activation profiles of human and chimpanzee CD4+ T-cells, including HLA-DR and CD62L. Moreover, we found that improved activation facilitated the replication of both CXCR4 and CCR5-tropic HIV-1 in CD4+ T-cell cultures from over 30 different chimpanzees. Thus, the previously reported “replication block” of CCR5-tropic HIV-1 in chimpanzee lymphocytes appears to be due, at least in large part, to suboptimal T-cell activation.     

Acquired Immunity to Malaria

Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.     

3q29 interstitial microdeletion syndrome: An inherited case associated with cardiac defect and normal cognition

An inherited, interstitial subtelomere deletion of approximately 1.3–1.4 Mb at 3q29 was identified in a patient and his father utilizing BAC array comparative genomic hybridization (a-CGH). The imbalance was located within the common 3q29 microdeletion syndrome region and shared the distal breakpoint with prior published cases. However, our patient was developmentally normal at 6 months of age and his father is a functional adult, who had mild developmental delay in childhood. They presented with congenital cardiac defects including patent ductus arteriosus. In addition, the patient had subvalvular aortic stenosis and his father had pulmonic stenosis. These defects were not present in most of the previously reported 3q29 microdeletion cases. This case expands the phenotypic findings associated with 3q29 microdeletion syndrome, suggesting an association with cardiac defect. It also raises the possibility of normal cognition in adulthood.