The impact of reconstruction algorithms and time of flight information on PET/CT image quality

Background

The aim of the study was to explore the influence of various time-of-flight (TOF) and non-TOF reconstruction algorithms on positron emission tomography/computer tomography (PET/CT) image quality.

Materials and methods.

Measurements were performed with a triple line source phantom, consisting of capillaries with internal diameter of ∼ 1 mm and standard Jaszczak phantom. Each of the data sets was reconstructed using analytical filtered back projection (FBP) algorithm, iterative ordered subsets expectation maximization (OSEM) algorithm (4 iterations, 24 subsets) and iterative True-X algorithm incorporating a specific point spread function (PSF) correction (4 iterations, 21 subsets). Baseline OSEM (2 iterations, 8 subsets) was included for comparison. Procedures were undertaken following the National Electrical Manufacturers Association (NEMA) NU-2-2001 protocol.

Results

Measurement of spatial resolution in full width at half maximum (FWHM) was 5.2 mm, 4.5 mm and 2.9 mm for FBP, OSEM and True-X; and 5.1 mm, 4.5 mm and 2.9 mm for FBP+TOF, OSEM+TOF and True-X+TOF respectively. Assessment of reconstructed Jaszczak images at different concentration ratios showed that incorporation of TOF information improves cold contrast, while hot contrast only slightly, however the most prominent improvement could be seen in background variability - noise reduction.

Conclusions

On the basis of the results of investigation we concluded, that incorporation of TOF information in reconstruction algorithm mostly affects reduction of the background variability (levels of noise in the image), while the improvement of spatial resolution due to incorporation of TOF information is negligible. Comparison of traditional and modern reconstruction algorithms showed that analytical FBP yields comparable results in some parameter measurements, such as cold contrast and relative count error. Iterative methods show highest levels of hot contrast, when TOF and PSF corrections were applied simultaneously.     

Nonlytic viral spread enhanced by autophagy components

The cell-to-cell spread of cytoplasmic constituents such as nonenveloped viruses and aggregated proteins is usually thought to require cell lysis. However, mechanisms of unconventional secretion have been described that bypass the secretory pathway for the extracellular delivery of cytoplasmic molecules. Components of the autophagy pathway, an intracellular recycling process, have been shown to play a role in the unconventional secretion of cytoplasmic signaling proteins. Poliovirus is a lytic virus, although a few examples of apparently nonlytic spread have been documented. Real demonstration of nonlytic spread for poliovirus or any other cytoplasmic constituent thought to exit cells via unconventional secretion requires demonstration that a small amount of cell lysis in the cellular population is not responsible for the release of cytosolic material. Here, we use quantitative time-lapse microscopy to show the spread of infectious cytoplasmic material between cells in the absence of lysis. siRNA-mediated depletion of autophagy protein LC3 reduced nonlytic intercellular viral transfer. Conversely, pharmacological stimulation of the autophagy pathway caused more rapid viral spread in tissue culture and greater pathogenicity in mice. Thus, the unconventional secretion of infectious material in the absence of cell lysis is enabled by components of the autophagy pathway. It is likely that other nonenveloped viruses also use this pathway for nonlytic intercellular spread to affect pathogenesis in infected hosts.Viruses have traditionally been classified as “nonlytic” (capable of exiting host cells without killing them) and “lytic” (exiting the host cell with concomitant cell lysis). Enveloped viruses such as hepatitis C, SARS coronavirus, and HIV acquire their envelopes and envelope proteins by budding through the ER, Golgi, and plasma membranes, respectively (1–3). After these budding events, the viral particles are either in a luminal compartment from which they reach the extracellular milieu via the conventional cellular secretion pathway or released directly outside of the cell.Nonenveloped viruses such as adenovirus, SV40, and picornaviruses assemble in nonlumenal compartments and would thus seem to have no exit pathway besides dismantling the host cell membrane. However, data consistent with nonlytic spread of such viruses (4, 5) and of other cytoplasmic aggregates continue to accumulate. Among picornaviruses, the spread of Theiler’s virus from infected neurons to surrounding glial cells occurs even in wlds mice, whose neurons are highly refractory to destruction (6). Both coxsackievirus B3 and hepatitis A virus (HAV) can spread between cells in the presence of neutralizing antibodies (7, 8). In fact, it is generally thought that HAV is released nonlytically (reviewed in ref. 9). Recently, the existence of infectious HAV particles within extracellular vesicles has been observed and shown to be dependent on proteins ALIX and VPS4B of the multivesicular body (MVB) pathway and independent of TSG101 or HRS from the MVB pathway as well Beclin-1 of the autophagy pathway (8). Finally, the release of cytoplasmic aggregates of huntingtin protein provides a nonviral example of potentially nonlytic spread (10). Documentation that such events are truly nonlytic, however, requires rigorous demonstration that no cell lysis occurred.Unconventional secretion, the release of cytoplasmic constituents without involvement of the Golgi apparatus or apparent lysis of the cell, can occur by several different mechanisms (reviewed in ref. 11). Nonvesicular routes include the direct exit of mammalian fibroblast growth factor 2 and yeast a-factor across the plasma membrane (12–14). Vesicle-mediated pathways of unconventional secretion include the release of cargo into the extracellular milieu from secretory lysosomes (15) or the budding of cytoplasmic constituents into the lumen of endosomal compartments using machinery from the endosomal complexes required for transport (ESCRT), from which they can subsequently be secreted as exosomes (reviewed in 16). Interestingly, a requirement for autophagy proteins (Atg 5, 7, 8, 11, and 12) was shown for the secretion of Dictyostelium discoideum and Saccharomyces cerevisiae sporulation pheromone (17, 18) and of mammalian IL-1β (19).We have hypothesized (20, 21) that poliovirus infection can spread via a route that employs elements of the autophagy pathway and the double-membraned topology of virus-induced cytoplasmic vesicles. Similarities between the membranous vesicles induced during infection with poliovirus and cellular autophagosomes include their ultrastructure, with two lipid bilayers surrounding lumen that contains cytosolic contents (22–24), and the colocalization of lipidated LC3, late endosomal LAMP-1, and lysosomal cathepsin (25). As part of their maturation, poliovirus-induced vesicles, like autophagosomes, become degradative due to fusion with endosomes and lysosomes (25). For autophagosomes, the subsequent destruction of the inner membrane is known to allow the pooling of luminal and cytoplasmic contents. We have reported previously that, for poliovirus, stimulation of autophagic processes by rapamycin increases both the intracellular yield and extracellular release of virus (20, 21). We proposed a mechanism by which viral release could be accomplished nonlytically: If an immature double-membraned vesicle that had entrapped virus-containing cytoplasm were to fuse with the plasma membrane, a membranous bleb that contained virus would be released. If the inner membrane had been degraded, the pooled luminal and cytoplasmic contents, including virus, would be released unbounded (Fig. 1A). We have termed this hypothesis “AWOL” (autophagosome-mediated exit without lysis) (21). However, it has been difficult to test this and other hypotheses concerning unconventional secretion because the use of cell populations makes it nearly impossible to exclude the possibility that lysis of a few cells is responsible for the release of cytoplasmic constituents (26). Here, we used live imaging of poliovirus-infected cells to show direct transfer of infection between living cells and a role for autophagic constituents in this nonlytic spread.Open in a separate windowFig. 1.Live-cell imaging of poliovirus-infected cells. (A) Proposed modes of spread for poliovirus. For most cell lines in tissue culture, lysis occurs 10–12 h after infection. The nonlytic route of viral spread proposed, a form of unconventional secretion, would result in the release of a few virus particles from a living cell, either from intact or ruptured inner compartments of autophagosome-like vesicles induced during infection. Pink cytoplasm indicates infection by PV-DsRed virus. The nucleus in the ruptured infected cell is blue, reflecting the use of the live-dead indicator in the experiments presented. The diffuse green in the uninfected cell represents the cytoplasmic form of GFP-LC3, whereas green puncta indicate the lipidation and membrane localization of GFP-LC3 in infected cells. (B) Single-cell images from Movie S1 of Huh7-A-1/GFP-LC3 cells infected with 2A-144-DsRed poliovirus (PV-DsRed) at a multiplicity of infection (MOI) of 0.1 PFU per cell and imaged every 12 min for 48 h, comparing GFP-LC3 puncta in uninfected (Upper) and infected (Lower). (C) Quantification of time-lapse imaging showing the percentage of cells with GFP-LC3 puncta over 48 h. For each time point, ∼100 cells were scored; data from two replicates are shown. (D) Time course data from one movie showing the percent of infected cells over time. Formation of GFP-LC3 puncta coincided with DsRed expression. (Scale bars: 25 μm.) ****P < 0.0001. (E) Single-cell images of Huh7-A-1/GFP-LC3 cells over 24 h of infection, showing both DsRed expression (Upper) and GFP-LC3 distribution (Lower). Arrows identify individual cells as GFP-LC3 puncta develop and viral infection progresses.     

前囊抛光对白内障术后视觉质量的影响

目的：评价前囊抛光对白内障超声乳化术后视觉质量的影响。

方法：前瞻性随机对照研究。纳入2021-11/2022-06于应急总医院眼科行白内障超声乳化联合人工晶状体(IOL)植入术的年龄相关性白内障患者65例73眼,随机分为抛光组(30例35眼,术中行前后囊联合抛光)和对照组(35例38眼,术中仅行后囊抛光)。观察术后1wk,1、3、6mo最佳矫正视力,术后3、6mo测量前囊口面积,并使用Pentacam三维眼前节系统评估后囊膜混浊程度(P评分)、IOL倾斜度和偏心量,使用OPD-Scan Ⅲ光程差分析系统评估波前像差、点扩散函数(PSF)的斯特列尔比(SR)和调制传递函数(MTF)。

结果：术后1wk,1、3、6mo,抛光组患者最佳矫正视力均优于对照组(P<0.05)。术后3、6mo,两组患者前囊口面积、后囊膜混浊程度(P评分)、IOL偏心量、PSF的SR值和MTF均无差异(P>0.05)。术后3mo,两组患者IOL倾斜度、波前像差均无差异(P>0.05),但术后6mo,抛光组IOL倾斜度小于对照组\〖(1.65±0.60)° vs(2.34±0.43)°,P<0.001)\〗,波前像差也小于对照组(0.03±0.01μm vs 0.06±0.03μm,P<0.001)。

结论：白内障超声乳化吸除术中行 360°抛光前后囊膜能提高术后最佳矫正视力,且术后IOL倾斜度更低、波前像差更小,视觉质量更好。     

Apparent Fibre Density: a novel measure for the analysis of diffusion-weighted magnetic resonance images

This article proposes a new measure called Apparent Fibre Density (AFD) for the analysis of high angular resolution diffusion-weighted images using higher-order information provided by fibre orientation distributions (FODs) computed using spherical deconvolution. AFD has the potential to provide specific information regarding differences between populations by identifying not only the location, but also the orientations along which differences exist. In this work, analytical and numerical Monte-Carlo simulations are used to support the use of the FOD amplitude as a quantitative measure (i.e. AFD) for population and longitudinal analysis. To perform robust voxel-based analysis of AFD, we present and evaluate a novel method to modulate the FOD to account for changes in fibre bundle cross-sectional area that occur during spatial normalisation. We then describe a novel approach for statistical analysis of AFD that uses cluster-based inference of differences extended throughout space and orientation. Finally, we demonstrate the capability of the proposed method by performing voxel-based AFD comparisons between a group of Motor Neurone Disease patients and healthy control subjects.A significant decrease in AFD was detected along voxels and orientations corresponding to both the corticospinal tract and corpus callosal fibres that connect the primary motor cortices. In addition to corroborating previous findings in MND, this study demonstrates the clear advantage of using this type of analysis by identifying differences along single fibre bundles in regions containing multiple fibre populations.     

产妇经血传播疾病检测对助产士职业暴露预防的意义

目的探讨产妇产前经血传播疾病检测对助产士职业暴露在医院感染控制中的意义。方法对2007年10月至2009年10月间的产妇进行乙型肝炎表面抗原（HBsAg）、丙型肝炎抗体（抗HCV）、艾滋病抗体（抗HIV）、甲苯胺红不加热血清试验（TRUST）检测,并对助产士在这两年间所发生的职业暴露进行统计分析。结果检出HBsAg阳性521例,阳性牢16．35％抗-HCV阳性4例,阳性率0．13％;抗-HIV阳性1例,阳性率0．03％;TRUST阳性12例,阳性率0．38％;助产士发生职业暴露5例,暴露率7．9％;经过随防一年,未发生医院院内感染。结论产前检测经血传播性疾病可事先知晓产妇经血传播疾病的感染情况,使助产士更严格遵循安全的操作流程,规范操作,自觉加强防护,对助产士职业暴露防治、对医院感染控制、对提高职业防护的依从性和执行率有着重要意义,大大降低助产士职业暴露的风险。     

Escherichia coli O157 infection and secondary spread, Scotland, 1999-2008

To determine the proportion of Escherichia coli O157 cases in Scotland attributable to secondary spread, we analyzed data obtained through entire-population enhanced surveillance. We identified 11% of cases as secondary. Secondary cases in single households were younger than secondary cases in outbreaks affecting >1 household and had similar risk for hemolytic uremic syndrome.     

双通道视觉质量分析系统可靠性评价及相关影响因素分析

目的 比较不同低阶像差矫正方式对双通道视觉质量分析系统测量结果影响,并分析影响其测量的相关因素.方法 在无其他眼病的67例单纯性屈光不正志愿者左右眼中随机选择一眼共67眼,分别使用传统框架眼镜矫正与双通道客观成像质量分析系统内置矫正方法进行光学成像质量和散射情况测量.比较两者MTF截止空间频率(MTF cutoff)、斯特列尔比值(strehl ratio,SR)、客观散射指数(objective scattering index,OSI)值差异,并分析造成两者测量差异原因.结果 传统框架眼镜矫正法与OQAS仪器内置矫正法测得的MTFcutoff值分别为(39.83±9.11)c· deg-1、(40.34±10.02)c·deg-1(t=-0.59,P=0.56);SR值分别为(0.22±0.06)c·deg-1、(0.22±0.06)c·deg-1(t=-0.90,P=0.37);OSI值分别为(0.50±0.06)c· deg-1、(0.40±0.05)c·deg-1(t=-2.96,P=0.004);两种矫正方法的最佳聚焦点等效球镜差值为(0.02 ±0.39)D,等效球镜度数符合率(相差≤0.50 D)为91％ (61/67).OSI差值与最佳聚焦点等效球镜差值存在负相关关系(r=-0.38,P ＜0.05).MTF cutoff差值与最佳聚焦点等效球镜差值存在正相关关系(r =0.54,P＜0.05).结论 双通道客观视觉质量分析系统内置的低阶像差矫正技术不影响光学质量评价,是一种临床上准确、可靠的视觉质量评估方法.     

Clinicopathological study on the intraductal spread of small pancreatic cancer

Background The aim of this study was to evaluate histopathologically the frequency, direction, and length of intraductal spread (IS) along the main pancreatic duct from the main tumor of small pancreatic cancer. Methods Resected specimens from 20 cases of pTS1 (histologically 2 cm or less in diameter) pancreatic cancer (September 1983 to December 2005) were examined histopathologically. As controls, 40 resected specimens from cases of pTS2 (more than 2 cm and less than 4 cm in diameter) or larger sized pancreatic cancer (pTS2≤) were examined in the same manner. The specimens were evaluated histopathologically as to (1) the prevalence of IS, (2) the direction and length of IS, and (3) the positive rates of transpapillary cytology of pure pancreatic juice (TPC) and biopsy of the main pancreatic duct (TPB), performed preoperatively. Results IS was observed in 45% of pTS1 and 13% of pTS2≤ cases. In 88% of cases of pTS1, IS was observed in the direction of the ampullary side. In 40% of cases of pTS2≤, IS toward the ampullary side was seen. The mean length of IS in pTS1 and pTS2≤ cases was 11.8 mm and 7.2 mm, respectively. Positive rates of TPC and TPB in pTS1 cases were 70% and 75%, respectively, and in pTS2≤ cases, 50% and 44%, respectively. Conclusions The frequency of IS was high in pTS1 cases, which suggests there is potential for improvement in establishing the histocytological diagnosis of small pancreatic cancer via the transpapillary approach with the development of adequate tools.     

ORF3 of porcine circovirus 2 enhances the in vitro and in vivo spread of the of the virus

The ORF3 protein of the pathogenic porcine circovirus 2 (PCV2) causes apoptosis of the virus-infected cells. In PCV2-infected piglets, ORF3 induces B and CD4 T lymphocyte depletion and lymphoid organ destruction and the ORF3-deficient PCV2 is attenuated in its pathogenicity (Virology, 383 (2009), 338). In addition to its role in causing the apoptosis of the immune cells, characteristic of the PCV2 infection associated disease conditions, the ORF3 also plays a role in the systemic dissemination of the PCV2 infection. Our experiments here show that ORF3 expedites the spread of the virus by inducing the early release of the virus from the infected cells. Further, in PCV2-infected mice, the ORF3-induced apoptosis also aids in recruiting macrophages to phagocytize the infected apoptotic cells leading to the systemic dissemination of the infection. The apoptotic activity of the ORF3 of PCV2 hence lends advantage to the spread of the virus.