A penalized likelihood approach for mixture cure models

Cure models have been developed to analyze failure time data with a cured fraction. For such data, standard survival models are usually not appropriate because they do not account for the possibility of cure. Mixture cure models assume that the studied population is a mixture of susceptible individuals, who may experience the event of interest, and non‐susceptible individuals that will never experience it. Important issues in mixture cure models are estimation of the baseline survival function for susceptibles and estimation of the variance of the regression parameters. The aim of this paper is to propose a penalized likelihood approach, which allows for flexible modeling of the hazard function for susceptible individuals using M‐splines. This approach also permits direct computation of the variance of parameters using the inverse of the Hessian matrix. Properties and limitations of the proposed method are discussed and an illustration from a cancer study is presented. Copyright © 2008 John Wiley & Sons, Ltd.     

Information criteria for Firth's penalized partial likelihood approach in Cox regression models

In the estimation of Cox regression models, maximum partial likelihood estimates might be infinite in a monotone likelihood setting, where partial likelihood converges to a finite value and parameter estimates converge to infinite values. To address monotone likelihood, previous studies have applied Firth's bias correction method to Cox regression models. However, while the model selection criteria for Firth's penalized partial likelihood approach have not yet been studied, a heuristic AIC‐type information criterion can be used in a statistical package. Application of the heuristic information criterion to data obtained from a prospective observational study of patients with multiple brain metastases indicated that the heuristic information criterion selects models with many parameters and ignores the adequacy of the model. Moreover, we showed that the heuristic information criterion tends to select models with many regression parameters as the sample size increases. Thereby, in the present study, we propose an alternative AIC‐type information criterion based on the risk function. A Bayesian information criterion type was also evaluated. Further, the presented simulation results confirm that the proposed criteria performed well in a monotone likelihood setting. The proposed AIC‐type criterion was applied to prospective observational study data. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd     

Efficient bias correction for magnetic resonance image denoising

Magnetic resonance imaging (MRI) is a popular radiology technique that is used for visualizing detailed internal structure of the body. Observed MRI images are generated by the inverse Fourier transformation from received frequency signals of a magnetic resonance scanner system. Previous research has demonstrated that random noise involved in the observed MRI images can be described adequately by the so‐called Rician noise model. Under that model, the observed image intensity at a given pixel is a nonlinear function of the true image intensity and of two independent zero‐mean random variables with the same normal distribution. Because of such a complicated noise structure in the observed MRI images, denoised images by conventional denoising methods are usually biased, and the bias could reduce image contrast and negatively affect subsequent image analysis. Therefore, it is important to address the bias issue properly. To this end, several bias‐correction procedures have been proposed in the literature. In this paper, we study the Rician noise model and the corresponding bias‐correction problem systematically and propose a new and more effective bias‐correction formula based on the regression analysis and Monte Carlo simulation. Numerical studies show that our proposed method works well in various applications. Copyright © 2012 John Wiley & Sons, Ltd.     

Investigating trial and treatment heterogeneity in an individual patient data meta-analysis of survival data by means of the penalized maximum likelihood approach

In a meta-analysis combining survival data from different clinical trials, an important issue is the possible heterogeneity between trials. Such intertrial variation can not only be explained by heterogeneity of treatment effects across trials but also by heterogeneity of their baseline risk. In addition, one might examine the relationship between magnitude of the treatment effect and the underlying risk of the patients in the different trials. Such a scenario can be accounted for by using additive random effects in the Cox model, with a random trial effect and a random treatment-by-trial interaction. We propose to use this kind of model with a general correlation structure for the random effects and to estimate parameters and hazard function using a semi-parametric penalized marginal likelihood method (maximum penalized likelihood estimators). This approach gives smoothed estimates of the hazard function, which represents incidence in epidemiology. The idea for the approach in this paper comes from the study of heterogeneity in a large meta-analysis of randomized trials in patients with head and neck cancers (meta-analysis of chemotherapy in head and neck cancers) and the effect of adding chemotherapy to locoregional treatment. The simulation study and the application demonstrate that the proposed approach yields satisfactory results and they illustrate the need to use a flexible variance-covariance structure for the random effects.     

Dissecting gene‐environment interactions: A penalized robust approach accounting for hierarchical structures

Identification of gene‐environment (G × E) interactions associated with disease phenotypes has posed a great challenge in high‐throughput cancer studies. The existing marginal identification methods have suffered from not being able to accommodate the joint effects of a large number of genetic variants, while some of the joint‐effect methods have been limited by failing to respect the “main effects, interactions” hierarchy, by ignoring data contamination, and by using inefficient selection techniques under complex structural sparsity. In this article, we develop an effective penalization approach to identify important G × E interactions and main effects, which can account for the hierarchical structures of the 2 types of effects. Possible data contamination is accommodated by adopting the least absolute deviation loss function. The advantage of the proposed approach over the alternatives is convincingly demonstrated in both simulation and a case study on lung cancer prognosis with gene expression measurements and clinical covariates under the accelerated failure time model.     

Penalized likelihood approach to estimate a smooth mean curve on longitudinal data

This paper aims to propose a penalized likelihood approach to estimate a smooth mean curve for the evolution with time of a Gaussian variable taking into account the correlation structure of longitudinal data. The model is an extension of the mixed effects linear model including an unspecified function of time f(t). The estimator (circumflex)f(t) is defined as the solution of the maximization of the penalized likelihood and is approximated on a basis of cubic M-spline with a reduced number of knots. We present modifications of four criteria (cross-validation, generalized cross-validation, T of Rice, Akaike's criterion) to estimate the smoothing parameter when data are correlated; these four criteria gave very similar results in the simulation study. The simulation study showed also the superiority of the Bayesian confidence bands of the mean curve over the frequentist ones. We develop empirical Bayes estimates of subject-specific deviations. This approach was applied to study the progression of CD4+ lymphocyte counts in a cohort of HIV patients treated with protease inhibitors.     

磁共振成像技术的进展

磁共振成像技术，通过近十余年的实践，证明它的优点非常突出，是一项尚待进一步完善和开发，很有潜力和崭新的影像学诊断检查手段，归纳起来，MIR技术近年来的发展，主要是快速扫描技术，磁共振频谱学检查，磁共振扩散（弥漫）加权成像技术（MRDWI）、磁共振血管造影术，磁共振成像造影剂，脑功能性MRI检查（FMRI）等。     

Gadofosveset-enhanced magnetic resonance angiography

Gadofosveset (Vasovist, Bayer Schering Pharma AG, Berlin/Germany) is the first intravascular contrast agent approved for use with magnetic resonance angiography in the European Union, Switzerland, Turkey, Canada, and Australia. Gadofosveset reversibly binds to albumin providing extended intravascular enhancement compared wth existing extracellular magnetic resonance contrast agents. Prior to approval, gadofosveset underwent extensive testing to evaluate the safety and efficacy of the drug; the clinical trials show that gadofosveset-enhanced magnetic resonance angiography (MRA) is safe and well tolerated in patients with vascular disease and effective for the detection of vascular stenosis and aneurysms gadofosveset has the potential to open new horizons in diagnostic MRA by increasing the spatial resolution and the robustness of MRA examinations and facilitating the examination of multiple vascular beds.     

骶髂关节炎MR检查中各成像序列的比较

目的探讨各MR成像序列显示骶髂关节炎病变的优势。资料与方法回顾分析55例典型强直性脊柱炎的骶髂关节MRI资料,扫描序列为SE-T1WI、TSE-T2WI、FFE-T2WI、SPIR,观察各序列对病变的显示情况,计算病变的显示率。结果FFE-T2WI序列显示关节软骨及骨质硬化最佳;SPIR序列对关节旁水肿最有优势;而对于骨关节面的侵蚀,SE-T1WI、TSE-T2WI、FFE-T2WI序列均可有较为满意的显示。     

儿童核磁共振成像检查过程中的心理护理

【目的】了解不同年龄层次儿童在核磁共振成像（magnetic resonance imaging．MRI）检查中的心理特点，有针对性地进行心理疏导，发挥心理护理在儿童MRI检查中的制动作用，提高扫描成功率，确保图像的清晰度。【方法】实验组对380例儿童MRI有效检查运用心理学方法，以4～14岁的受检儿童作为心理护理对象，使之在MRI检查中消除不良心理因素。对照组搜集62例相应年龄段受检儿童，不予施加任何心理护理作为对照。【结果】实验组4～6岁受检儿童有效制动109例，占73．6％。7～11岁的受检儿童有效制动195例，占93.8％。12～14岁的受检儿童有效制动76例，占97．4％。两组各年龄段间有效制动率的差异均有非常显著性（P值〈0．01）。【结论】心理护理可以提高儿童MRI检查的成功率，保证图像的质量．缩短检查时间，提高检查效率，是一种实用、安全、可靠的制动方法。     

A survey of the likelihood approach to bioequivalence trials

Bioequivalence (BE) trials are abbreviated clinical trials whereby a generic drug or new formulation is evaluated to determine if it is 'equivalent' to a corresponding previously approved brand-name drug or formulation. In this paper, we survey the process of testing BE and advocate the likelihood paradigm for representing the resulting data as evidence. We emphasize the unique conflicts between hypothesis testing and confidence intervals in this area--which we believe are indicative of the existence of the systemic defects in the frequentist approach--that the likelihood paradigm avoids. We suggest the direct use of profile likelihoods for evaluating BE. We discuss how the likelihood approach is useful to present the evidence for both average and population BE within a unified framework. We also examine the main properties of profile likelihoods and estimated likelihoods under simulation. This simulation study shows that profile likelihoods offer a viable alternative to the (unknown) true likelihood for a range of parameters commensurate with BE research.     

Validation of accuracy in image co-registration with computed tomography and magnetic resonance imaging in Gamma Knife radiosurgery

The latest version of Leksell GammaPlan (LGP) is equipped with Digital Imaging and Communication in Medicine (DICOM) image-processing functions including image co-registration. Diagnostic magnetic resonance imaging (MRI) taken prior to Gamma Knife treatment is available for virtual treatment pre-planning. On the treatment day, actual dose planning is completed on stereotactic MRI or computed tomography (CT) (with a frame) after co-registration with the diagnostic MRI and in association with the virtual dose distributions. This study assesses the accuracy of image co-registration in a phantom study and evaluates its usefulness in clinical cases. Images of three kinds of phantoms and 11 patients are evaluated. In the phantom study, co-registration errors of the 3D coordinates were measured in overall stereotactic space and compared between stereotactic CT and diagnostic CT, stereotactic MRI and diagnostic MRI, stereotactic CT and diagnostic MRI, and stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. In the clinical study, target contours were compared between stereotactic MRI and diagnostic MRI co-registered with stereotactic CT. The mean errors of coordinates between images were < 1 mm in all measurement areas in both the phantom and clinical patient studies. The co-registration function implemented in LGP has sufficient geometrical accuracy to assure appropriate dose planning in clinical use.     

氨基质子饱和转移磁共振成像方法研究

目的:探讨氨基质子饱和转移磁共振成像。方法:介绍化学交换饱和转移磁共振成像的理论、特征以及所受干扰因素等。结果:作为一种新型的分子水平的磁共振成像技术,氨基质子饱和转移磁共振成像是一种可以对人体的蛋白质以及与化学交换效应相关的交换速率进行高分辨成像的技术,也是一种内源性的无创的分子成像方法,具有重要的研究与应用价值。结论:氨基质子饱和转移磁共振成像可以被安全地应用于脑肿瘤以及脑中风等临床科学研究中。     

磁共振在肾癌患者诊断中的影像学特点及应用价值

目的探讨磁共振(magnetic resonance imaging,MRI)在肾癌患者诊断中的影像学特点及应用价值。方法回顾性分析深圳市龙华区人民医院收治的50例肾癌患者的临床资料,分别予以其MRI检查和动态增强扫描,依次执行T1加权像(T1 weighted image,T1WI)、T2WI检查序列。总结MRI在肾癌患者诊断中的影像学特点。结果存在18例T1WI均匀等信号患者,27例混杂信号患者,5例均匀低信号患者;存在20例T2WI均匀略高信号,5例明显高信号患者,25例以高信号为主的混杂信号患者;11例假包膜者;14例肾周侵犯、16例肾窦侵犯及3例肾静脉癌栓,13例腹膜后或肾门淋巴结肿大患者。经造影剂行MRI增强扫描,存在非均匀强化患者22例,病灶均匀强化患者18例,以内壁不规则为主要表现的环状强化6例。结论MRI在肾癌患者诊断中具有明显的影像学特点,可结合临床评估患者的预后。     

磁共振成像中涡流的补偿方法研究

在磁共振成像过程中,涡流是影响图像质量的重要因素之一。本文分析了永磁型磁共振仪中涡流产生的原因,介绍了几种常用的涡流补偿方法,并提出一种快速的涡流预增强补偿参数调试方法。通过在XGYOPER-0.3型磁共振仪上进行实验,对涡流进行了有效的补偿,明显提高了图像质量。     

冲动控制任务时对立违抗性障碍儿童的功能核磁共振研究

【目的】探索对立违抗性障碍（oppositional defiant disorder，ODD）儿童冲动控制任务时的脑功能特点。【方法】10例ODD和10例对照组男童，以GOSTOP冲动控制为刺激任务，进行功能性核磁共振成像（functional magnetic resonance imaging，fMRI）；然后对两组数据标准化、合并和平均；比较两组脑激活图像的分布和各个激活区域的面积。【结果】两组儿童大脑的额极（额中回、额下回和眶部前部）和部分颞极（颞下回、颞中回）明显激活，两组激活区域分布没有质的差异；对照组在以上相关区域激活较集中，其他脑区激活少；ODD组在以上区域激活面积大于对照组，此外还可见其他多处皮质和皮质下结构被激活。【结论】额极在冲动行为控制中扮演重要角色；ODD组比对照组需要动用更多的额极及其他脑区参与冲动控制任务，提示ODD儿童额极功能相对低下。     

A likelihood approach to estimating sensitivity and specificity for binocular data: application in ophthalmology

Binocular data typically arise in ophthalmology where pairs of eyes are evaluated, through some diagnostic procedure, for the presence of certain diseases or pathologies. Treating eyes as independent and adopting the usual approach in estimating the sensitivity and specificity of a diagnostic test ignores the correlation between eyes. This may consequently yield incorrect estimates, especially of the standard errors. The paper proposes a likelihood-based method of accounting for the correlations between eyes and estimating sensitivity and specificity using a model for binocular or paired binary outcomes. Estimation of model parameters via maximum likelihood is outlined and approximate tests are provided. The efficiency of the estimates is assessed in a simulation study. An extension of the methodology to the case of several diagnostic tests, or the same test measured on several occasions, which arises in multi-reader studies, is given. A further extension to the case of multiple diseases is outlined as well. Data from a study on diabetic retinopathy are analysed to illustrate the methodology.     

运动区占位性病变患者皮质功能重组的功能磁共振成像研究

目的采用功能磁共振成像(fMRI)技术研究运动区占位性病变患者皮质功能区的重组特征以及评估患者运动功能障碍的风险。方法选择23例中央沟附近占位性病变患者和9例健康志愿者进行磁共振常规扫描和fMRI检查。结果占位半球对侧手主动对指运动时,fMRI显示占位侧初级运动皮层(M1)区激活、移位者20例,被激活的M1区体积比占位半球同侧手运动激活体积小者15例,占位对侧正常半球内M1区出现代偿性激活者13例,两侧前运动皮层(PMC)次级运动中枢激活区增大者9例;3例患手肌力明显下降,其中被动简单对指运动M1区能激活的有2例,1例无法激活。结论fMRI可直观地观察患者运动皮质功能区的改变及重组,对评估患者运动功能状态有重要的临床意义。     

A nonparametric likelihood test for detecting discordance between two measurements with application to censored viral load determinations

Patient management frequently involves quantitative evaluation of a patient's attributes. For example, in HIV studies, a high viral load can be a trigger to initiate or modify an antiretroviral therapy. At times, a new method of evaluation may substitute for an established one, provided that the new method does not result in different clinical decisions compared with the old method. Traditional measures of agreement between the two methods are inadequate for deciding if a new method can replace the old. Especially, when the data are censored by a detection limit, estimates of agreement can be biased unless the distribution for the censored data is correctly specified; this is usually not feasible in practice. We propose a nonparametric likelihood test that seamlessly handles censored data. We further show that the proposed test is a generalization of the test on nominal measurement concordance to continuous measurement. An exact permutation procedure is proposed for implementing the test. Our application is an HIV study to determine whether one method of processing plasma samples can safely substitute for the other. The plasma samples are used to determine viral load and a large portion of data are left censored due to a lower detection limit. Copyright (c) 2008 John Wiley & Sons, Ltd.     

基于模糊聚类空间模型的非均匀MR图像分割

模糊C-均值聚类算法（FCM）已广泛地运用到MR图像的分割中。但传统的算法中未利用图像的空间信息，在分割叠加了噪声和附加了偏移场的非均匀MR图像时分割效果不理想。本文改进了传统FCM的目标函数，引入控制邻域作用紧密程度的参数，提出了一种能够更加合理地运用图像的空间信息，改进的模糊C-均值聚类算法。通过对脑部MR图像的分割实验表明，该算法能够比传统的FCM和其它改进算法对非均匀图像进行更精确的分割。