Iterative reconstruction algorithm improves the image quality without affecting quantitative measurements of computed tomography perfusion in the upper abdomen.

OBJECTIVE: To investigate differences between reconstruction algorithms in quantitative perfusion values and time-attenuation curves in computed tomography perfusion (CTP) examinations of the upper abdomen. METHODS: Twenty-six CTP examinations were reconstructed with filtered back projection and an iterative reconstruction algorithm, advanced modeled iterative reconstruction (ADMIRE), with different levels of noise-reduction strength. Using the maximum-slope model, quantitative measurements were obtained: blood flow (mL/min/100 mL), blood volume (mL/100 mL), time to peak (s), arterial liver perfusion (mL/100 mL/min), portal venous liver perfusion (mL/100 mL/min), hepatic perfusion index (%), temporal maximum intensity projection (Hounsfield units (HU)) and temporal average HU. Time-attenuation curves for seven sites (left liver lobe, right liver lobe, hepatocellular carcinoma, spleen, gastric wall, pancreas, portal vein) were obtained. Mixed-model analysis was used for statistical evaluation. Image noise and the signal:noise ratio (SNR) were compared between four reconstructions, and statistical analysis of these reconstructions was made with a related-samples Friedman's two-way analysis of variance by ranks test. RESULTS: There were no significant differences for quantitative measurements between the four reconstructions for all tissues. There were no significant differences between the AUC values of the time-attenuation curves between the four reconstructions for all tissues, including three automatic measurements (portal vein, aorta, spleen). There was a significant difference in image noise and SNR between the four reconstructions. CONCLUSIONS: ADMIRE did not affect the quantitative measurements or time-attenuation curves of tissues in the upper abdomen. The image noise was lower, and the SNR higher, for iterative reconstructions with higher noise-reduction strengths.

Vaccination with tumor cells pulsed with foreign peptide induces immunity to the tumor itself.

EMT-6 mammary carcinoma and B16 melanoma (B16M) cells are lethal and barely immunogenic in syngeneic BALB/c and C57BL/6 mice, respectively. We show that mice vaccinated with tumor cells pulsed with a MHC class I-restricted peptide develop a T cell response, not only to the peptide, but also to the unpulsed tumor. These mice display protective immunity against the unpulsed tumor, and their T cells adoptively transfer tumor-specific protection to immunodeficient SCID mice. Our data have implications for cancer vaccine strategies. Grafting a single well-defined foreign peptide on tumor cells might suffice to trigger anti-tumor immunity.

T cell immunity induced by live, necrotic, and apoptotic tumor cells.

The rules that govern the engagement of antitumor immunity are not yet fully understood. Ags expressed by tumor cells are prone to induce T cell tolerance unless the innate immune system is activated. It is unclear to what extent tumors engage this second signal link by the innate immune system. Apoptotic and necrotic (tumor) cells are readily recognized and phagocytosed by the cells of the innate immune system. It is unknown how this affects the tumor's immunogenicity. Using a murine melanoma (B16m) and lymphoma (L5178Y-R) model, we studied the clonal sizes and cytokine signatures of the T cells induced by these tumors in syngeneic mice when injected as live, apoptotic, and necrotic cells. Both live tumors induced a type 2 CD4 cell response characterized by the prevalent production of IL-2, IL-4, and IL-5 over IFN-gamma. Live, apoptotic, and necrotic cells induced CD4 (but no CD8) T cells of comparable frequencies and cytokine profiles. Therefore, live tumors engaged the second signal link, and apoptotic or necrotic tumor cell death did not change the magnitude or quality of the antitumor response. A subclone of L5178Y-R, L5178Y-S cells, were found to induce a high-frequency type 1 response by CD4 and CD8 cells that conveyed immune protection. The data suggest that the immunogenicity of tumors, and their characteristics to induce type 1 or type 2, CD4 or CD8 cell immunity is not primarily governed by signals associated with apoptotic or necrotic cell death, but is an intrinsic feature of the tumor itself.

Protective efficacy of anti-Helicobacter pylori immunity following systemic immunization of neonatal mice.

Helicobacter pylori infection of the gastric mucosa is a significant cause of morbidity and mortality because of its etiologic role in symptomatic gastritis, peptic ulcer disease, and gastric adenocarcinoma. Infection occurs in young children; therefore, a prophylactic vaccine would have to be administered within the first year of life, a period thought to be immunologically privileged. We investigated vaccine formulations administered by different routes to confer protective anti-H. pylori immunity in neonatal mice. Neonatal mice immunized with a single dose of vaccine in complete Freund's adjuvant (CFA) generated antigen-specific gamma interferon-, interleukin-2 (IL-2)-, IL-4-, and IL-5-secreting T cells in numbers similar to those in immunized adult mice, while vaccine administered to neonates in incomplete Freund's adjuvant (IFA) induced such cells in reduced numbers compared to those in adult mice. Both IFA and CFA, however, provided partial protection from a challenge with infectious H. pylori when the vaccine was administered subcutaneously. Neonatal immunized mice also had reduced bacterial loads when immunized intraperitoneally with CFA. In all cases, protection was equivalent to that achieved when adult counterparts were immunized. These studies suggest that an efficacious vaccine might be successfully administered to very young children to prevent perinatal infection of H. pylori.