Quantitative evaluation of block-iterative reconstruction image in PET: comparison of the dynamic RAMLA algorithm and OSEM algorithm

PURPOSE: Iterative reconstruction has been successfully used in whole-body PET imaging because of reductions in noise and scanning time. However, there are plural algorithms for image reconstruction such as OSEM, RAMLA and Dynamic RAMLA. Dynamic RAMLA (DRAMA) is an iterative algorithm similar to RAMLA, but the relaxation parameter is controlled in such a way that the propagation of noise from projection data to the reconstructed image. The purpose of this study was to investigate differences in the DRAMA and OSEM algorithms, in terms of real space and frequency space. METHOD: A whole-body torso phantom (NEMA image-quality phantom) filled with F-18 was scanned with a dedicated PET scanner. The smallest four spheres, with internal diameters of 10, 13, 17, and 22 mm, were filled with F-18 at an 8:1 concentration with respect to the background. The two largest spheres, with diameters of 28 and 37 mm, were not filled with water (empty). The emission scan for a 50 cm axial range varied from 5-20 minutes, to examine the effect of the count statistics on the quality of the reconstructed images. The images were reconstructed with OSEM by changing the number of subsets from 1 to 128 in each study. As to the number of iterations, both iterative reconstruction algorithms were one. As a reference standard, images with maximum counts (60 minutes) were reconstructed with a filtered-back projection method. The quality of the reconstructed images was evaluated in terms of contrast, background variability, and two-dimensional power spectrum analysis. RESULTS: As for the real space results, OSEM with more than 32 subsets decreased contrast because of images with checkerboard noise. The DRAMA algorithm provided stable contrast even when count statistics were poor. A two-dimensional power spectrum analysis also revealed that the OSEM algorithm enhanced noise components in reconstruction with more than 32 subsets. CONCLUSION: Our preliminary data suggested that the OSEM algorithm requires few iterations with a small number of subsets for whole-body imaging. However, the DRAMA algorithm provides a reasonable signal-to-noise ratio with satisfactory spatial resolution even with one iteration. Especially in clinical whole-body PET, DRAMA was most useful because of its fast convergence and small computer burden.     

The sinusoidal pressure during ischemia-reperfusion injury in perfused mouse liver pretreated with or without L-NAME

BACKGROUND: Hepatic ischemia-reperfusion (I/R) is accompanied by liver weight gain and ascites formation possibly caused by an increase in the sinusoidal pressure, a determinant of hepatic transvascular fluid movement. However, changes in the sinusoidal pressure during hepatic I/R in mice are not known. It is also controversial whether nitric oxide (NO) exerts a beneficial or detrimental effect on hepatic I/R injury. We determined the changes in hepatic sinusoidal pressure and liver weight, and the effect of a NO synthase inhibitor, N(G)-nitro-L-arginine methyl ester (L-NAME) on I/R injury of isolated mouse liver. MATERIALS AND METHODS: Isolated liver from 20 male outbred ddY mice was perfused portally with diluted blood (Hct 3%). After pretreatment with L-NAME (100 microm) or D-NAME (100 microm), ischemia was induced at room temperature by occlusion of the inflow line of the portal vein for 1 h followed by 1-h reperfusion in a recirculating manner. The sinusoidal pressure was assessed by the double vascular occlusion pressure (Pdo), and pre- and postsinusoidal resistance was determined. Liver injury was assessed by blood levels of alanine aminotransferase (ALT). RESULTS: In the d-NAME group (n=7), immediately after reperfusion, the portal pressure increased by 2.8 +/- 0.1 (SE) mmHg, which was accompanied by an increase in Pdo of 1.5 +/- 0.1 mmHg, indicating increases in pre- and postsinusoidal resistance to a similar degree. Then, presinusoidal, but not postsinusoidal, resistance sustained increased until 60 min after reperfusion. Liver weight increased to 0.14 +/- 0.04 g/g liver after reperfusion, followed by a gradual return to baseline. Blood ALT levels increased at 60 min after reperfusion. There were no significant differences in changes in the variables between the D- and L-NAME (n=7) groups. In the time-matched non- I/R control group (n=6), no changes in variables were observed for 2 h. CONCLUSIONS: Mouse hepatic I/R causes marginal liver weight gain associated with a small and transient increase in the sinusoidal pressure, and nitric oxide does not play any significant roles in this injury.     

Age at time of corticosteroid administration is a risk factor for osteonecrosis in pediatric patients with systemic lupus erythematosus: A prospective magnetic resonance imaging study

Objective

To clarify whether age at the time of the initial administration of corticosteroids is a risk factor for corticosteroid‐associated osteonecrosis in children with systemic lupus erythematosus (SLE), using magnetic resonance imaging (MRI).

Methods

From 1986 to 2007, MRI was used to prospectively study 676 joints, including 72 joints (36 hips and 36 knees) in 18 pediatric patients with SLE (<15 years old), 100 joints (50 hips and 50 knees) in 25 adolescent patients with SLE (15–20 years old), and 504 joints (252 hips and 252 knees) in 126 adult patients with SLE (>20 years old), beginning just after corticosteroid administration, for at least 1 year. The followup rate was 100%.

Results

In pediatric patients, osteonecrosis developed in 4 joints (6%; all hips). In adolescent patients, osteonecrosis developed in 49 joints (49%; 18 hips and 31 knees). In adult patients, osteonecrosis developed in 207 joints (41%; 95 hips and 112 knees). The rate of osteonecrosis was significantly lower in pediatric patients than in adolescent or adult patients (P = 0.0001). Logistic regression analysis revealed that adolescent and adult patients had a significantly higher risk for osteonecrosis compared with pediatric patients, with an odds ratio of 10.3 (P < 0.0001). The youngest patients with osteonecrosis in the hip and knee were 14.9 years old and 15.5 years old, respectively. Osteonecrosis did not develop in patients younger than age 14 years.

Conclusion

Our results suggest that age at the time of the initial administration of corticosteroids is associated with osteonecrosis in pediatric patients with SLE.

     

Development, worsening, and improvement of diabetic microangiopathy in older people: six-year prospective study of patients under intensive diabetes control

OBJECTIVES: To examine retinopathy and nephropathy in elderly patients with diabetes mellitus (DM) under intensive multifactorial DM control. DESIGN: Six-year interventional observation study. SETTING: Multicenter study including four hospitals. PARTICIPANTS: Four hundred thirteen elderly (> or = 65) patients with type 2 DM attending each hospital for 1 year or longer; those receiving hemodialysis or with uncured malignancy were excluded. MEASUREMENTS: Development, worsening, and improvement of retinopathy and nephropathy and respective risk factors. RESULTS: The mean baseline hemoglobin (HbA1c), blood pressure (BP), and total cholesterol were 6.8%, 137/74 mmHg, and 5.13 mmol/L, respectively. Retinopathy developed in 45 of 168 (27%) patients and, of 63 with nonproliferative retinopathy, worsened and improved in 11 (17%) and 23 (37%), respectively. Nephropathy developed in 53 of 227 (23%) patients and improved in 13 of 51 (25%) having it baseline. The mean change in glomerular filtration rate (DeltaGFR, baseline GFR-GFR at the end of the study period) in those with nephropathy at baseline was 21.5 mL/min. HbA1c was related to development of retinopathy (P=.001, odds ratio (OR)=1.91), and serum creatinine (P=.03, OR=1.02), systolic BP (SBP) (P=.03, OR=1.22), and prior stroke (P=.005, OR=3.21) were related to development of nephropathy. In patients with nephropathy at baseline, SBP (P=.03, Spearman's rho (rho)=0.310), total cholesterol (P=.01, rho=0.361), and low-density lipoprotein cholesterol (P=.03, rho=0.322) were correlated with DeltaGFR. CONCLUSION: In elderly patients under intensive control for DM, the outcome of microangiopathy is favorable. Modifiable risk factors were hyperglycemia for development of retinopathy and hypertension and hypercholesterolemia for development or worsening of nephropathy; prior stroke was an unmodifiable risk factor for development of nephropathy.     

Activin A Causes Cancer Cell Aggressiveness in Esophageal Squamous Cell Carcinoma Cells

BACKGROUND: Expression of activin A is associated with lymph node metastasis and clinical stage in esophageal cancer. METHODS: To clarify the aggressive behavior of tumors with high activin A expression, we used the beta subunit of activin A to establish stable activin betaA (Act-betaA)-transfected carcinoma cells in two human esophageal carcinoma cell lines, KYSE110 and KYSE140. The biological behavior of these cells was compared with that in mock-transfected cells from the same cell lines. We focused our attention on cell growth and tumorigenesis, and proliferation and apoptosis. RESULTS: Both Act-betaA-transfected carcinoma cell lines showed a higher growth rate than the mock-transfected carcinoma cells. In an in vitro invasion assay and a xenograft analysis, the Act-betaA-transfected carcinoma cells showed far higher proliferation in vitro and a higher potency for tumorigenesis in vivo, respectively. Moreover, in an analysis of apoptosis via Fas stimulation, the Act-betaA-transfected carcinoma cells showed a higher tolerance to apoptosis compared with the mock-transfected carcinoma cells. Moreover, anti-activin-neutralizing antibody-treated squamous cell cancer cell lines inhibited their migration. CONCLUSIONS: Collectively, these data indicate that continuous high expression of activin A in esophageal carcinoma cells is not related to tumor suppression, but rather to tumor progression in vitro and in vivo. The inhibition of activin might be one of the methods to attenuate tumor aggressiveness.     

Downbeat positioning nystagmus is a common clinical feature despite variable phenotypes in an FHM1 family

Clinical examinations and mutational analyses were carried out in three patients of a Japanese familial hemiplegic migraine (FHM) pedigree. Each affected member demonstrated a broad clinical spectrum that included hemiplegic migraine with progressive cerebellar ataxia, migraine without aura, and episodic ataxia. Despite this variability, all members exhibited marked downbeat positioning nystagmus, and magnetic resonance images (MRI) all showed cerebellar atrophy predominantly of the cerebellar vermis. All affected members had a T666M missense mutation in the protein encoded by the CACNA1A gene (calcium channel, voltage-dependent, P/Q type, alpha 1A subunit). Although clinical features associated with the T666M CACNA1A mutation are highly variable, downbeat positioning nystagmus may be an important clinical feature of this disease.     

Hypermethylation of MCAM gene is associated with advanced tumor stage in prostate cancer

BACKGROUND: DNA methylation has emerged as a promising biomarker for prostate cancer detection. In this report, we screened 36 candidate genes generated by a bioinformatic analysis of the human genome, and found that the melanoma cell adhesion molecule (MCAM) was an excellent candidate for cancer-specific methylation in prostate cancer. METHODS: Direct sequencing of bisulfite-treated genomic DNA, conventional methylation-specific PCR (MSP), real-time quantitative methylation-specific PCR, immunohistochemistry, colony formation assay, and statistical analysis. RESULTS: We found that the melanoma cell adhesion molecule (MCAM) gene promoter was specifically methylated in prostate cancer cell lines and primary prostate cancer (PCa) but not in non-neoplastic prostate (BPH) tissues by direct sequencing of bisulfite-treated genomic DNA and conventional methylation-specific PCR (MSP). Further analysis with quantitative MSP showed greater hypermethylation of the MCAM promoter (80%, 70/88) in primary prostate cancer compared to 12.5% (3/24) in BPH. Prostatic intraepithelial neoplasias (PIN), potential precursors of prostate carcinoma, showed an intermediate methylation rate of 23% (7/30). We further observed that MCAM promoter methylation was directly correlated with tumor stage (pT3+pT4) (P = 0.001) and Gleason score (P = 0.018) in primary prostate carcinoma. CONCLUSIONS: Our results suggest that MCAM promoter hypermethylation deserves further attention as a potential diagnostic prostatic DNA marker in human prostate cancer.     

Lymph Node Metastasis Density and Growth Pattern as Independent Prognostic Factors in Advanced Esophageal Squamous Cell Carcinoma

BACKGROUND: Esophageal cancer is one of the leading types of cancer, and it is a particularly deadly form of malignancy. TNM classification is the most common staging system, but it has been reported that prognosis is not reflected adequately by this classification. The purpose of this study was to clarify independent prognostic factors in esophageal squamous cell carcinoma (ESCC), a dominant type of esophageal cancer in Japan, to broaden the staging system to improve its predictive value. Thus staging could be expanded to make the prognosis a valuable clinical tool, and to improve knowledge of the biological traits of advanced ESCC. METHODS: The present study included 121 patients with advanced ESCC (stage II to IVA) treated by esophagectomy between 1990 and 2003 at the Kitasato University Higashi Hospital. RESULTS: Univariate prognostic analysis of the disease-specific survival revealed that TNM stage (p < 0.0001), lymph node metastasis density over 10% (ND10; p < 0.0001), R-category (p = 0.003), intramural metastasis within the esophagus (IM; p = 0.009), growth pattern (p = 0.01), and size of tumor (p = 0.02) were significantly associated with a poor outcome in advanced ESCC. Multivariate analysis confirmed that growth pattern (p = 0.02, HR = 3.1) and ND10 (p = 0.02, HR = 2.0) were finally remnant prognostic factors independent of TNM stage. Growth pattern was prominent in stage II, whereas ND10 was directly proportional to stage progression and characteristics to stage IV disease. Interestingly, ND20, the most malignant phenotype of ESCC, was the only prognostic determinant, even in stage IV disease. CONCLUSIONS: From the present study, we concluded that progression of lymph node density is characteristic of a life-threatening phenotype of advanced ESCC, and it should be employed as a therapeutic target to improve patient survival. Growth pattern is an alternative target characteristic of less advanced ESCC. Both of these parameters may be applied as useful clinical tools in the management of patients with advanced esophageal cancer.