Statistical image reconstruction from correlated data with applications to PET

Most statistical reconstruction methods for emission tomography are designed for data modeled as conditionally independent Poisson variates. In reality, due to scanner detectors, electronics and data processing, correlations are introduced into the data resulting in dependent variates. In general, these correlations are ignored because they are difficult to measure and lead to computationally challenging statistical reconstruction algorithms. This work addresses the second concern, seeking to simplify the reconstruction of correlated data and provide a more precise image estimate than the conventional independent methods. In general, correlated variates have a large non-diagonal covariance matrix that is computationally challenging to use as a weighting term in a reconstruction algorithm. This work proposes two methods to simplify the use of a non-diagonal covariance matrix as the weighting term by (a) limiting the number of dimensions in which the correlations are modeled and (b) adopting flexible, yet computationally tractable, models for correlation structure. We apply and test these methods with simple simulated PET data and data processed with the Fourier rebinning algorithm which include the one-dimensional correlations in the axial direction and the two-dimensional correlations in the transaxial directions. The methods are incorporated into a penalized weighted least-squares 2D reconstruction and compared with a conventional maximum a posteriori approach.     

Humoral immune responses during experimental infection with <Emphasis Type="Italic">Fascioloides magna</Emphasis> and <Emphasis Type="Italic">Fasciola hepatica</Emphasis> in goats and comparison of their excretory/secretory products

This study investigated the humoral immune responses of goats experimentally infected with Fascioloides magna and Fasciola hepatica to F. magna excretory/secretory products (FmESP) or F. hepatica excretory/secretory products (FhESP), respectively. An enzyme-linked immunosorbent assay (ELISA) was used to determine serum antibody responses and for possible discrimination of F. magna and F. hepatica infections in goats. Comparison of ESPs of both flukes and evaluation of ESP antigenicity was also studied applying immunoblotting techniques. In all infected goats, antibody level was significantly increased (against negative control) since 2 weeks post infection (WPI). However, the dynamics of antibodies varied between F. magna and F. hepatica groups during the course of the infection. The cross-reaction of antibodies developed against F. magna and F. hepatica with ESP proteins was recorded by ELISA. The species-specific proteins 40, 120 kDa from FmESP and 80, 160 kDa from FhESP (with no antibody cross-reaction) were detected by two dimensional electrophoresis and immunoblot as the potential immunodiagnostic markers. Our results suggest that F. magna and F. hepatica infection could be distinguished by common immunological techniques based on species-specific antigen–antibodies interaction.     

CCR2 regulates development of Theiler's murine encephalomyelitis virus-induced demyelinating disease

Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a murine model for multiple sclerosis, involves recruitment of T cells and macrophages to the CNS after infection. We hypothesized that CCR2, the only known receptor for CCL2, would be required for TMEV-induced demyelinating disease development because of its role in macrophage recruitment. TMEV-infected SJL CCR2 knockout (KO) mice showed decreased long-term clinical disease severity and less demyelination compared with controls. Flow cytometric data indicated that macrophages (CD45(high) CD11b(+) ) in the CNS of TMEV-infected CCR2 KO mice were decreased compared with control mice throughout disease. CD4(+) and CD8(+) T cell percentages in the CNS of TMEV-infected control and CCR2 KO mice were similar over the course of disease. There were no apparent differences between CCR2 KO and control peripheral immune responses. The frequency of interferon-gamma-producing T cells in response to proteolipid protein 139-151 in the CNS was also similar during the autoimmunity stage of TMEV-induced demyelinating disease. These data suggest that CCR2 is important for development of clinical disease by regulating macrophage accumulation after TMEV infection.     

Behavioural and ERP indices of response inhibition during a Stop-signal task in children with two subtypes of Attention-Deficit Hyperactivity Disorder.

Previous research has shown that children with Attention-Deficit Hyperactivity Disorder of the Combined Type (AD/HDcom) have problems with response inhibition, with poorer task performance and atypical inhibition-related ERPs relative to control subjects, while little is known about response inhibition in children with Attention-deficit Hyperactivity Disorder of the Predominantly Inattentive Type (AD/HDin). In this study children with AD/HDin (N=12), AD/HDcom (N=13) and age-matched controls (N=13) aged between 8 and 14 years completed a Stop-signal task, with visual Go and auditory Stop-signal stimuli, while EEG was recorded. The results indicated that the groups did not differ on any inhibitory task performance measure, but the AD/HD groups showed more errors of omission to Go stimuli than controls. ERPs to the visual Go stimuli differed between children with AD/HDin and controls (increased central N1 and N2, decreased central P2 and increased parietal P3), while the AD/HDcom group showed only minor scalp distribution differences for N2 and P3. The AD/HDin group showed amplitude differences from controls to Stop signals (larger central N1 and parietal P3; reduced midline N2) and did not show a Successful vs. Failed inhibition effect for P3. The AD/HDcom group showed reduced parietal P3 to Stop signals, with the Trial Type effect present for N2 but not P3. These data suggest that the apparent atypical inhibitory processing at N2 and P3 may stem, at least in part, from atypical early sensory/alerting processing of all stimuli in children with AD/HDin.     

Kutane B-Zell-Lymphome

Primary cutaneous B-cell lymphomas include cutaneous follicle centre lymphoma (PCFCL), cutaneous marginal zone B-cell lymphoma (PCMZL) and cutaneous diffuse large B-cell lymphoma (PCLBCL) "leg type" which are the three main types in the new WHO-EORTC classification for cutaneous lymphomas. PCFCL and PCMZL are indolent lymphomas with an excellent prognosis while PCLBCL shows an aggressive clinical course. All three types must be distinguished from a secondary skin involvement by systemic lymphomas. Since histological and immunohistochemical findings are not decisive, making this distinction requires appropriate staging procedures. In contrast, the pathologist can make an important contribution to the differential diagnosis between neoplastic and reactive cutaneous lymphoproliferations.     

Characterization of Anaplasma phagocytophilum major surface protein 5 and the extent of its cross-reactivity with A. marginale

Major surface protein 5 (Msp5) of Anaplasma marginale is highly conserved in the genus Anaplasma and the antigen used in a commercially available competitive enzyme-linked immunosorbent assay (cELISA) for serologic identification of cattle with anaplasmosis. This study analyzes the degrees of conservation of Msp5 among various isolates of Anaplasma phagocytophilum and the extent of serologic cross-reactivity between recombinant Msp5 (rMsp5) of Anaplasma marginale and A. phagocytophilum. The msp5 genes from various isolates of A. phagocytophilum were sequenced and compared. rMsp5 proteins of A. phagocytophilum and A. marginale were used separately in an indirect ELISA to detect cross-reactivity in serum samples from humans and dogs infected with A. phagocytophilum and cattle infected with A. marginale. Serum samples were also tested with a commercially available competitive ELISA that uses monoclonal antibody ANAF16C1. There were 100% sequence identities in the msp5 genes among all of the A. phagocytophilum isolates from the United States and a horse isolate from Sweden. Sheep isolates from Norway and dog isolates from Sweden were 99% identical to one another but differed in 17 base pairs from the United States isolates and the horse isolate. Serologic cross-reactivity was identified when serum samples from cattle infected with A. marginale were reacted with rMsp5 of A. phagocytophilum and when serum samples from humans and dogs infected with A. phagocytophilum were reacted with rMsp5 of A. marginale in an indirect-ELISA format. Serum samples from dogs or humans infected with A. phagocytophilum did not cross-react with rMsp5 of A. marginale when tested with the commercially available cELISA. These results suggest that rMsp5 of A. phagocytophilum is highly conserved among United States and European isolates and that serologic distinction between A. phagocytophilum and A. marginale infections cannot be accomplished if rMsp5 from either organism is used in an indirect ELISA.     

Role of interleukin-6 in a glucan-induced model of granulomatous vasculitis

The role of interleukin-6 (IL-6) in granulomatous vasculitis is not well understood. To investigate its involvement in this type of vasculitis a model of glucan-induced pulmonary vasculitis employed interleukin-6 deficient (IL-6-/-) mice. Briefly, IL-6-/- mice and C57B/J6 wild type (IL-6+/+) mice were injected intravenously with a suspension of glucan isolated from the cell wall of bakers yeast which results in a granulomatous vasculitis primarily in the pulmonary vasculature. Histological examination demonstrated no significant difference in the number of infiltrating leukocytes between the IL-6+/+ and IL-6-/- glucan-injured mice. Similar numbers of granulomas were noted in both the IL-6+/+ and IL-6-/- injured animals, while no granulomas were seen in saline injected control mice. Cells recovered from the bronchoalveolar lavage (BAL) fluid were differentially stained and counted. While there was a significant increase in infiltrating leukocytes recovered from the BAL following glucan-induced injury, there was no significant difference between the IL-6+/+ and IL-6-/- mice. In addition, no difference was demonstrated in total protein content in the BAL fluid between IL-6+/+ and IL-6-/- mice. However, myeloperoxidase (MPO) activity in the lungs of the IL-6-/- mice was less than in their IL-6+/+ counterparts suggesting that these animals have a partial defect in their ability to recruit neutrophils in this model. Studies done to look for levels of other cytokines/chemokines in these animals to compensate for the loss of IL-6 revealed that only IL-10 in the sera (p<0.016) and BAL fluid (p<0.05) of IL-6-/- mice was significantly higher then their IL-6+/+-injured counterparts. These studies suggest that IL-6, while possibly involved in early neutrophil accumulation in this model does not appear critical to the development of the TH-2 mediated granulomatous vasculitis.     

The relationship between historical aspirin-induced asthma and severity of asthma induced during oral aspirin challenges

BACKGROUND: Historical aspirin- or nonsteroidal anti-inflammatory drug (NSAID)-induced reactions might provide predictive information about the severity of reactions in patients with aspirin-exacerbated respiratory disease (AERD) undergoing oral aspirin challenge (OAC). OBJECTIVE: We sought to assess the relationship between historical aspirin- or NSAID-induced bronchial reactions and the severity of bronchial reactions during OAC in patients with AERD. METHODS: Data regarding the provoking doses, treatments, and treatment settings of historical aspirin/NSAID-induced reactions were recorded, analyzed, and compared with the provoking doses, maintenance regimens, and observed decreases in FEV(1) that occurred during OAC in 210 consecutive patients referred with suspected AERD. RESULTS: Of 147 patients who reported seeking acute medical care for their historical aspirin/NSAID-induced asthma attacks, 101 (69%) were treated in an emergency department and released, and 46 (31%) required hospitalization. During OAC in these 147 subjects, 23 (16%) had a 20% to 29% decrease and 14 (10%) had a 30% or greater decrease in FEV(1) values from baseline. Of the 46 patients previously hospitalized for aspirin/NSAID-induced asthma attacks, 9 (20%) had a 20% to 29% decrease and 6 (13%) had a 30% or greater decrease in FEV(1) during OAC. By contrast, of the 63 patients who treated their prior aspirin/NSAID-induced reactions at home, 5 (8%) had a 20% to 29% decrease and 5 (8%) had a 30% or greater decrease in FEV(1) during OAC (P = not significant for both). CONCLUSION: The severity of the historical aspirin/NSAID-induced asthma attack was not predictive of asthma severity during OAC. CLINICAL IMPLICATIONS: These data provide further reassurance regarding the safety of outpatient aspirin desensitization.     

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE epsilon4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-epsilon4 and 12 epsilon4 subjects. The epsilon4 group displayed greater activation than the non-epsilon4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE epsilon4-related deficiencies associated with verbal episodic memory encoding and consolidation.