TIPS bilateral noise reduction in 4D CT perfusion scans produces high-quality cerebral blood flow maps

Cerebral computed tomography perfusion (CTP) scans are acquired to detect areas of abnormal perfusion in patients with cerebrovascular diseases. These 4D CTP scans consist of multiple sequential 3D CT scans over time. Therefore, to reduce radiation exposure to the patient, the amount of x-ray radiation that can be used per sequential scan is limited, which results in a high level of noise. To detect areas of abnormal perfusion, perfusion parameters are derived from the CTP data, such as the cerebral blood flow (CBF). Algorithms to determine perfusion parameters, especially singular value decomposition, are very sensitive to noise. Therefore, noise reduction is an important preprocessing step for CTP analysis. In this paper, we propose a time-intensity profile similarity (TIPS) bilateral filter to reduce noise in 4D CTP scans, while preserving the time-intensity profiles (fourth dimension) that are essential for determining the perfusion parameters. The proposed TIPS bilateral filter is compared to standard Gaussian filtering, and 4D and 3D (applied separately to each sequential scan) bilateral filtering on both phantom and patient data. Results on the phantom data show that the TIPS bilateral filter is best able to approach the ground truth (noise-free phantom), compared to the other filtering methods (lowest root mean square error). An observer study is performed using CBF maps derived from fifteen CTP scans of acute stroke patients filtered with standard Gaussian, 3D, 4D and TIPS bilateral filtering. These CBF maps were blindly presented to two observers that indicated which map they preferred for (1) gray/white matter differentiation, (2) detectability of infarcted area and (3) overall image quality. Based on these results, the TIPS bilateral filter ranked best and its CBF maps were scored to have the best overall image quality in 100% of the cases by both observers. Furthermore, quantitative CBF and cerebral blood volume values in both the phantom and the patient data showed that the TIPS bilateral filter resulted in realistic mean values with a smaller standard deviation than the other evaluated filters and higher contrast-to-noise ratios. Therefore, applying the proposed TIPS bilateral filtering method to 4D CTP data produces higher quality CBF maps than applying the standard Gaussian, 3D bilateral or 4D bilateral filter. Furthermore, the TIPS bilateral filter is computationally faster than both the 3D and 4D bilateral filters.     

Pre-existent vertebral rotation in the human spine is influenced by body position

Both the humans as well as the quadrupedal spine have been shown to exhibit a pattern of pre-existent rotation that is similar in direction to what is found in the most common types of idiopathic scoliosis. It has been postulated that human bipedalism introduces forces to the spine that increase a tendency of the vertebrae to rotate. The objective of this study was to examine the effect of body position on vertebral rotation in vivo. Thirty asymptomatic volunteers underwent magnetic resonance imaging scanning of the spine (T2–L5) in three different body positions; upright, quadrupedal-like (on hands-and-knees) and supine. Vertebral rotation in the local transverse plane was measured according to a pre-established method and compared at different spinal levels between the three body positions. It was shown that in all three positions the mid- and lower thoracic vertebrae were predominantly rotated to the right. However, vertebral rotation was significantly less in the quadrupedal position than in both the standing upright and supine positions.     

Two cases of Robertsonian translocations in oligozoospermic males and their consequences for pregnancies induced by intracytoplasmic sperm injection

Two case histories are presented documenting structural chromosome abnormalities in infertile males. The abnormalities were detected only after application of intracytoplasmic sperm injection (ICSI) was repeatedly unsuccessful or resulted in an abnormal pregnancy. A mosaic Robertsonian translocation 45,XY,der(13;13)(q10; q10)/46,XY,t(13;13)(p10;p10), der(13p;13p) incompatible with normal offspring was found in a male with extreme oligozoospermia after three subsequent ICSI treatments were unsuccessful and one had resulted in a spontaneous abortion. A second case involved a Robertsonian translocation 45,XY,der(13;14)(q10;q10) which was detected in a male with extreme oligozoospermia after ultrasound abnormalities were found in an ICSI-induced twin pregnancy. Amniocentesis showed an unbalanced 46,XY,+13,der(13;14)(q10;q10) karyotype in one twin and a Robertsonian 45,XX,der(13;14)(q10;q10) karyotype in the other twin. Chromosome analysis of males with abnormal sperm characteristics is advised prior to ICSI.      

Bispecific-armed, interferon gamma-primed macrophage-mediated phagocytosis of malignant non-Hodgkin's lymphoma

To show that macrophages can be effectively targeted against malignant B cells, bispecific antibodies (BsAb) were constructed from two antibodies having specificity for the high-affinity Fc receptor for IgG (Fc gamma RI/CD64) and the B-cell differentiation antigens CD19 and CD37. Using a flow cytometry-based assay and confocal imaging, we show that these constructs mediated significant phagocytosis of B lymphocytes by macrophages that could be enhanced with interferon gamma (IFN gamma) and IFN gamma in combination with macrophage colony- stimulating factor. BsAb-dependent phagocytosis was triggered through Fc gamma RI and could be blocked only by using F(ab')2 fragments from the parent molecule or by cross-linking Fc gamma RI. BsAb-dependent phagocytosis was not blocked by antibodies to the other Fc receptors, Fc gamma RII and Fc gamma RIII. Because these antibody constructs bind to an epitope outside the Fc gamma RI ligand binding site, we show that autologous serum, polyclonal IgG, and monomeric IgG1 did not block BsAb- dependent phagocytosis, whereas autologous serum and the IgG fractions blocked parent molecule monoclonal antibody-dependent phagocytosis due to the avid binding of monomeric IgG to Fc gamma RI. Finally, BsAb- mediated phagocytosis was effective against the malignant B cells of patients with mantle cell lymphoma, prolymphocytic leukemia, and chronic lymphocytic leukemia. Based on these studies, we propose that BsAbs may provide an effective means of immunomodulation for patients with B-cell malignancies.     

Helicobacter pylori stimulates inducible nitric oxide synthase expression and activity in a murine macrophage cell line

BACKGROUND & AIMS: Helicobacter pylori uniquely colonizes the human stomach and produces gastric mucosal inflammation. High-output nitric oxide production by inducible nitric oxide synthase (iNOS) is associated with immune activation and tissue injury. Because mononuclear cells comprise a major part of the cellular inflammatory response to H. pylori infection, the ability of H. pylori to induce iNOS in macrophages was assessed. METHODS: H. pylori preparations were added to RAW 264.7 murine macrophages, and iNOS expression was assessed by Northern blot analysis, enzyme activity assay, and NO2- release. RESULTS: Both whole H. pylori and French press lysates induced concentration-dependent NO2- production, with peak levels 20-fold above control. These findings were paralleled by marked increases in iNOS messenger RNA and enzyme activity levels. iNOS expression was synergistically increased with interferon gamma, indicating that the H. pylori effect can be amplified by other macrophage-activating factors. Studies of lipopolysaccharide (LPS) content and polymyxin B inhibition of LPS suggested that the H. pylori effect was attributable to both LPS- dependent and -independent mechanisms. CONCLUSIONS: iNOS expression in macrophages is activated by highly stable H. pylori products and may play an important role in the pathogenesis of H. pylori-associated gastric mucosal disease. (Gastroenterology 1996 Dec;111(6):1524-33)     

What radiation dose for DLA-identical canine marrow grafts? [published erratum appears in Blood 1989 Feb;73(2):624]

In view of reported attempts at marrow grafting after nuclear accidents with a broad range of radiation exposures, the present study explored the total-body irradiation (TBI) conditions needed for engraftment in a canine model by using marrow from DLA-identical littermates. Previous studies have shown that such grafts are consistently successful when recipients are exposed to 920 cGy of TBI delivered at a rate of 7 cGy/min from opposing dual cobalt sources. The present TBI doses were all in the lethal range. Five dogs were administered 450 cGy; seven dogs, 600 cGy; five dogs, 700 cGy; and five dogs, 800 cGy of TBI administered at 7 cGy/min. They received a median of 3.3 x 10(8) marrow cells/kg intravenously after completion of radiation. Results showed transient allogeneic marrow engraftment in all dogs administered the lowest dose of TBI studied (450 cGy). Importantly, transient grafts permitted four of five dogs to live long enough for autologous marrow recovery to occur. At increasing radiation doses, 600, 700, and 800 cGy, the risk of graft failure lessened, with 3 of 7, 2 of 5, and 1 of 5 dogs, respectively, showing graft rejection. Fewer dogs survived with autologous marrow recovery, and more showed sustained allogeneic engraftment (4 of 7, 3 of 5, and 4 of 5 dogs, respectively). We conclude that DLA-identical littermate marrow grafts are beneficial in the setting of otherwise lethal radiation exposures, with most dogs either experiencing sustained allogeneic engraftment or surviving with autologous marrow recovery due to the extended support provided by a transient allogeneic graft.     

In vitro regulation of immunoglobulin synthesis after marrow transplantation. I. T-cell and B-cell deficiencies in patients with and without chronic graft-versus-host disease

Twenty-four patients with aplastic anemia or acute leukemia were treated by marrow grafts from HLA-identical donors after conditioning with high doses of cyclophosphamide and/or today body irradiation. They were studied between 4 and 63 mo (median 14.2) after transplantation. Seventeen patients had chronic graft-versus-host disease (C-GVHD) and 7 were healthy. They were studied for defects in their T- and B-cell function using and indirect hemolytic plaque assay for Ig production after 6 days of culture in the presence of pokeweek mitogen. T or B cells from the patients with or without C-GVHD were cocultured with T or B cells from their HLA-identical marrow donors or unrelated normal controls. Intrinsic B-cell defects, lack of helper T-cell activity, and suppressor T-cell activity were more frequently found in patients with C-GVHD than in healthy patients. Fifteen of the 17 patients with C-GVHD showed on or more defects in their T-and B-cell function compared to only 3 of the 7 patients without C-GVHD. None of the healthy controls, including the marrow donors, showed defects in their T- and B-cell functions. These in vitro findings may be helpful in assessing the process of immune reconstitution and the immunologic aberration found after human marrow transplantation.