Differentiating BOLD and non-BOLD signals in fMRI time series using multi-echo EPI

A central challenge in the fMRI based study of functional connectivity is distinguishing neuronally related signal fluctuations from the effects of motion, physiology, and other nuisance sources. Conventional techniques for removing nuisance effects include modeling of noise time courses based on external measurements followed by temporal filtering. These techniques have limited effectiveness. Previous studies have shown using multi-echo fMRI that neuronally related fluctuations are Blood Oxygen Level Dependent (BOLD) signals that can be characterized in terms of changes in R(2)* and initial signal intensity (S(0)) based on the analysis of echo-time (TE) dependence. We hypothesized that if TE-dependence could be used to differentiate BOLD and non-BOLD signals, non-BOLD signal could be removed to denoise data without conventional noise modeling. To test this hypothesis, whole brain multi-echo data were acquired at 3 TEs and decomposed with Independent Components Analysis (ICA) after spatially concatenating data across space and TE. Components were analyzed for the degree to which their signal changes fit models for R(2)* and S(0) change, and summary scores were developed to characterize each component as BOLD-like or not BOLD-like. These scores clearly differentiated BOLD-like "functional network" components from non BOLD-like components related to motion, pulsatility, and other nuisance effects. Using non BOLD-like component time courses as noise regressors dramatically improved seed-based correlation mapping by reducing the effects of high and low frequency non-BOLD fluctuations. A comparison with seed-based correlation mapping using conventional noise regressors demonstrated the superiority of the proposed technique for both individual and group level seed-based connectivity analysis, especially in mapping subcortical-cortical connectivity. The differentiation of BOLD and non-BOLD components based on TE-dependence was highly robust, which allowed for the identification of BOLD-like components and the removal of non BOLD-like components to be implemented as a fully automated procedure.     

An investigation of the value of spin-echo-based fMRI using a Stroop color-word matching task and EPI at 3 T

This study examines the value of spin-echo-based fMRI for cognitive studies at the main magnetic field strength of 3 T using a spin-echo EPI (SE-EPI) sequence and a Stroop color-word matching task. SE-EPI has the potential advantage over conventional gradient-echo EPI (GE-EPI) that signal losses caused by dephasing through the slice are not present, and hence although image distortion will be the same as for an equivalent GE-EPI sequence, signal voids will be eliminated. The functional contrast in SE-EPI will be lower than for GE-EPI, as static dephasing effects do not contribute. As an auxiliary experiment interleaved diffusion-weighted and non-diffusion-weighted SE-EPI was performed in the visual cortex to further elucidate the mechanims of functional contrast. In the Stroop experiment activation was detected in all areas previously found using GE-EPI. Additional frontopolar and ventral frontomedian activations were also found, which could not be detected using GE-EPI. The experiments from visual cortex indicated that at 3 T the BOLD signal change has contributions from the extravascular space and larger blood vessels in roughly equal amounts. In comparison with GE-EPI the absence of static dephasing effects would seem to result in a superior intrinsic spatial resolution. In conclusion the sensitivity of SE-EPI at 3 T is sufficient to make it the method of choice for fMR studies that require a high degree of spatial localization or where the requirement is to detect activation in regions affected by strong susceptibility gradients.     

MRT2弛豫时间定量测定在研究关节软骨生物组织构成中的价值

目的探讨MRT2弛豫时间定量测定在研究关节软骨生物组织构成中的价值。方法20名健康成年男性志愿者和19名骨性关节炎（Osteoarthritis,OA）患者行膝关节矢状位TSE序列8回波扫描,在获得的图像上进行关节软骨B值的测量,分析志愿者软骨浅深层T2值、志愿者与OA患者的T2值之间差异。结果志愿者胫骨面关节软骨浅层的平均B值为（48．8±6．3）ms,深层的平均T2值为（44．3±5．7）ms;股骨面则为（52．1±5．7）ms和（47．7±5．3）ms,差异有统计学意义。（t=3．148和t=3．384,P〈0．01）,相应的T2图显示了B值的这种空间分布趋势。OA患者胫骨关节软骨的平均T2值为（56．0±9．1）ms,较健康志愿者膝关节胫骨关节软骨浅层的平均T2值要高,差异有统计学意义（t=3．446,P〈0．01）。结论应用MRT2弛豫时间定量测定可研究关节软骨生物组织构成及其变化,具有临床应用价值。     

Anatomy and time course of discrimination and categorization processes in vision: an fMRI study

Studies investigating the cerebral areas involved in visual processes generally oppose either different tasks or different stimulus types. This work addresses, by fMRI, the interaction between the type of task (discrimination vs. categorization) and the type of stimulus (Latin letters, well-known geometrical figures, and Korean letters). Behavioral data revealed that the two tasks did not differ in term of percentage of errors or correct responses, but a delay of 185 ms was observed for the categorization task in comparison with the discrimination task. All conditions activated a common neural network that includes both striate and extrastriate areas, especially the fusiform gyri, the precunei, the insulae, and the dorsolateral frontal cortex. In addition, interaction analysis revealed that the right insula was sensitive to both tasks and stimuli, and that stimulus type induced several significant signal variations for the categorization task in right frontal cortex, the right middle occipital gyrus, the right cuneus, and the left and right fusiform gyri, whereas for the discrimination task, significant signal variations were observed in the right occipito-parietal junction only. Finally, analyzing the latency of the BOLD signal also revealed a differential neural dynamics according to tasks but not to stimulus type. These temporal differences suggest a parallel hemisphere processing in the discrimination task vs. a cooperative interhemisphere processing in the categorization task that may reflect the observed differences in reaction time.     

Normal variation of magnetic resonance T1 relaxation times in the human population at 1.5 T using ShMOLLI

Background

Quantitative T1-mapping is rapidly becoming a clinical tool in cardiovascular magnetic resonance (CMR) to objectively distinguish normal from diseased myocardium. The usefulness of any quantitative technique to identify disease lies in its ability to detect significant differences from an established range of normal values. We aimed to assess the variability of myocardial T1 relaxation times in the normal human population estimated with recently proposed Shortened Modified Look-Locker Inversion recovery (ShMOLLI) T1 mapping technique.

Methods

A large cohort of healthy volunteers (n = 342, 50% females, age 11–69 years) from 3 clinical centres across two countries underwent CMR at 1.5T. Each examination provided a single average myocardial ShMOLLI T1 estimate using manually drawn myocardial contours on typically 3 short axis slices (average 3.4 ± 1.4), taking care not to include any blood pool in the myocardial contours. We established the normal reference range of myocardial and blood T1 values, and assessed the effect of potential confounding factors, including artefacts, partial volume, repeated measurements, age, gender, body size, hematocrit and heart rate.

Results

Native myocardial ShMOLLI T1 was 962 ± 25 ms. We identify the partial volume as primary source of potential error in the analysis of respective T1 maps and use 1 pixel erosion to represent “midwall myocardial” T1, resulting in a 0.9% decrease to 953 ± 23 ms. Midwall myocardial ShMOLLI T1 was reproducible with an intra-individual, intra- and inter-scanner variability of ≤2%. The principle biological parameter influencing myocardial ShMOLLI T1 was the female gender, with female T1 longer by 24 ms up to the age of 45 years, after which there was no significant difference from males. After correction for age and gender dependencies, heart rate was the only other physiologic factor with a small effect on myocardial ShMOLLI T1 (6ms/10bpm). Left and right ventricular blood ShMOLLI T1 correlated strongly with each other and also with myocardial T1 with the slope of 0.1 that is justifiable by the resting partition of blood volume in myocardial tissue. Overall, the effect of all variables on myocardial ShMOLLI T1 was within 2% of relative changes from the average.

Conclusion

Native T1-mapping using ShMOLLI generates reproducible and consistent results in normal individuals within 2% of relative changes from the average, well below the effects of most acute forms of myocardial disease. The main potential confounder is the partial volume effect arising from over-inclusion of neighbouring tissue at the manual stages of image analysis. In the study of cardiac conditions such as diffuse fibrosis or small focal changes, the use of “myocardial midwall” T1, age and gender matching, and compensation for heart rate differences may all help to improve the method sensitivity in detecting subtle changes. As the accuracy of current T1 measurement methods remains to be established, this study does not claim to report an accurate measure of T1, but that ShMOLLI is a stable and reproducible method for T1-mapping.     

Comparison of sustained and transient activity in children and adults using a mixed blocked/event-related fMRI design

The ability to make direct comparisons between adult and child neuroimaging data is important to the study of the neural basis of cognitive development. Recent fMRI studies in adults have used mixed blocked/event-related designs to extract activity consistent with separable sustained, task-related processes and transient, trial-related processes. Because brain regions with different time courses of activity may have different roles in cognitive processing, the ability to distinguish between sustained and transient signals would contribute to understanding the functional roles of regions involved in cognitive processing. The developmental profile of such activity would give insight into how cognitive processing develops over time. The purpose of this study was to assess the utility of the mixed design to detect and dissociate sustained and transient activity in children, and to determine if the time courses or magnitudes of the extracted signals differ from those extracted from adults. An fMRI experiment was performed on 10 adults and 10 children (ages 7-8) using counterphase flickering checkerboard stimuli that produced sustained, transient, and a combination of sustained and transient responses in visual cortex. Analyses were performed using the general linear model (GLM) assuming a shape for sustained effects, but not for transient effects. In visual cortex, neither transient nor sustained effects showed significant between-group differences. For both groups, flickering checkerboard stimuli produced robust responses in visual cortex contralateral but not ipsilateral to the stimulus. Results extend the feasibility of direct statistical comparison of adults and children; mixed designs provide a means to examine neural activity in both adults and children related to sustained, task-level processes, likely related to task-level control.     

合成磁共振成像不同带宽对T1、T2及PD测量值的影响—体膜研究

目的 观察多动态多回波序列(multi-dynamic multi-echo,MDME)不同带宽对T1、T2及质子密度(proton density,PD)测量值的影响.材料与方法 3种具有不同T1、T2及PD的体膜[脑灰质(gray matter,GM),白质(white matter,WM),脑脊液(cerebro...     

良、恶性软组织肿块超声造影表现分析

目的 探讨良、恶性软组织肿块超声造影剂灌注时间-强度曲线特点.方法 对37例软组织肿块进行超声造影检查,用Q-LAB软件对感兴趣区造影动态图像进行伽马回归(Gamma-Variate)曲线拟合,进行定量分析,并与病理诊断对照,分析良、恶性病变的超声造影表现及增强特征.结果 37例软组织肿块经病理诊断确定良性21例,恶性16例.良性组肿块主要为均匀性增强(19/21)或无增强(2/21),恶性组肿块主要表现为均匀性增强(10/16)及不均匀性增强(6/16).良、恶性软组织肿块在曲线上造影剂到达时间(AT)及达峰时间(TTP)差异无统计学意义(P均＞0.05),而良性肿块的上升支斜率(A)及峰值强度(DPI)明显小于恶性肿块(P＜0.05).结论 超声造影时间-强度曲线分析能显示良、恶性软组织肿块的造影剂增强情况,对临床鉴别诊断有一定价值.     

Exploring the discrimination power of the time domain for segmentation and characterization of active lesions in serial MR data

This paper presents a new method for the automatic segmentation and characterization of object changes in time series of three-dimensional data sets. The technique was inspired by procedures developed for analysis of functional MRI data sets. After precise registration of serial volume data sets to 4-D data, we applied a time series analysis taking into account the characteristic time function of variable lesions. The images were preprocessed with a correction of image field inhomogeneities and a normalization of the brightness over the whole time series. Thus, static regions remain unchanged over time, whereas changes in tissue characteristics produce typical intensity variations in the voxel's time series. A set of features was derived from the time series, expressing probabilities for membership to the sought structures. These multiple sources of uncertain evidence were combined to a single evidence value using Dempster-Shafer's theory. The project was driven by the objective of improving the segmentation and characterization of white matter lesions in serial MR data of multiple sclerosis patients. Pharmaceutical research and patient follow-up requires efficient and robust methods with a high degree of automation. The new approach replaces conventional segmentation of series of 3-D data sets by a 1-D processing of the temporal change at each voxel in the 4-D image data set. The new method has been applied to a total of 11 time series from different patient studies, covering time resolutions of 12 and 24 data sets over a period of about 1 year. The results demonstrate that time evolution is a highly sensitive feature for detection of fluctuating structures.     

采用组织芯片技术检测大肠癌组织中p16、cyclinD1和CDK4的表达

目的研究大肠癌组织中多肿瘤抑制蛋白(p16)、细胞周期蛋白(cyclinD1)及细胞周期蛋白依赖激酶(CDK4)的表达及其意义.方法采用组织芯片技术制作80例大肠癌组织芯片,同时用S-P免疫组织化学方法检测大肠癌组织芯片中p16、cyclinD1和CDK4的表达.结果 80例大肠癌中p16、cyclinD1和CDK4的阳性率分别为40.0%、57.5%、47.5%.不同组织学类型、淋巴结转移状况的大肠癌中,p16、cyclinD1的表达无明显差异(P＞0.05).不同组织学类型、浸润程度及淋巴结转移状况的大肠癌中CDK4的表达均无明显差异(P＞0.05).结论 p16表达、cyclinD1高表达与大肠癌的浸润程度密切相关,大肠癌中p16低表达与cyclinD1的高表达密切相关.p16低表达影响cyclinD1的高表达.应用组织芯片大规模高效检测临床组织样本是可行的,具有快速、方便经济、准确的特点.     

骨髓间充质干细胞联合可降解支架体外构建组织工程带瓣静脉

背景：临床上治疗慢性静脉功能不全的主要方法是静脉瓣膜修复及带瓣静脉段移植,但这些方法创伤较大,且带瓣静脉来源有限。组织工程学和再生医学在修复病变血管方面取得的进步,而以自体来源的内皮细胞为种子细胞的组织工程带瓣静脉也见于了报道,但存在排出反应。 目的：构建一个有可自我更新、修复、类似天然瓣膜结构并具有功能的带瓣静脉。 方法：麻醉取Beagle犬的骨髓获取骨髓间充质干细胞,采用密度梯度离心和贴壁法获取骨髓间充质干细胞,并进行细胞的传代、冻存复苏、流式细胞仪检测和定向诱导分化。采用热致相分离技术,以聚（乳酸-乙醇酸）共聚物为基材,利用自制带瓣静脉模具制备三维组织工程带瓣静脉支架,制备组织工程带瓣静脉支架,并研究其形态结构。将骨髓间充质干细胞种植在支架上构建可降解的带瓣静脉,在体外培养2周。 结果与结论：扫描电镜观察显示支架孔隙率高。培养的细胞符合骨髓间充质干细胞的形态特征,培养的细胞大部分表达CD29和CD44,不表达CD34和CD45。细胞毒性实验显示支架无毒性,有利于细胞增殖和迁移。将细胞种植在支架表面上培养后可形成单层细胞层。体外实验验证细胞支架复合物的瓣膜有一定的开闭功能。利用三维聚（乳酸-乙醇酸）共聚物支架和骨髓间充质干细胞可成功构建组织工程带瓣静脉,组织工程带瓣静脉将有可能作为静脉瓣膜的的替代物治疗静脉瓣膜疾病。     

采用组织芯片技术检测大肠癌组织中p16、cyclinDl和CDK4的表达

目的研究大肠癌组织中多肿瘤抑制蛋白(p16)、细胞周期蛋白(cyclinD1)及细胞周期蛋白依赖激酶(CDK4)的表达及其意义。方法采用组织芯片技术制作80例大肠癌组织芯片,同时用S-P免疫组织化学方法检测大肠癌组织芯片中p16、cyclinD1和CDK4的表达。结果80例大肠癌中p16、cyclinD1和CDK4的阳性率分别为40.0%、57.5%、47.5%。不同组织学类型、淋巴结转移状况的大肠癌中,p16、cyclinD1的表达无明显差异(P>0.05)。不同组织学类型、浸润程度及淋巴结转移状况的大肠癌中CDK4的表达均无明显差异(P>0.05)。结论p16表达、cyclinD1高表达与大肠癌的浸润程度密切相关,大肠癌中p16低表达与cyclinD1的高表达密切相关。p16低表达影响cyclinD1的高表达。应用组织芯片大规模高效检测临床组织样本是可行的,具有快速、方便经济、准确的特点。     

Quantitative inversion time prescription for myocardial late gadolinium enhancement using T1-mapping-based synthetic inversion recovery imaging: reducing subjectivity in the estimation of inversion time

To develop a quantitative T1-mapping-based synthetic inversion recovery (IR_synth) approach to calculate the optimal inversion time (TI₀) for late gadolinium enhancement (LGE) imaging. Prospectively enrolled patients (n?=?130, 58?±?16 years) underwent cardiac MRI on a 1.5T system including Look-Locker TI-scout (LL), modified LL IR (MOLLI)-based T1-mapping, and LGE acquisitions. Patients were randomized into two groups: LL group (TI-scout followed T1-mapping) or MOLLI group (T1-mapping followed TI-scout). In both groups, the second acquisition was used to determine the TI₀ for LGE. IR_synth images were generated from T1-maps between TI?=?200–400 ms in 5 ms increments. Image quality was rated on a 3-point scale and the remote/background signal intensity ratio (SIR) was calculated. In the LL group (n?=?53), the TI-scout-based TI₀ was significantly shorter compared to IR_synth [230 ms (219–242) vs. 280 ms (263–297), P?<?0.0001]. The TI₀ used for LGE was set 30–40 ms longer [261 ms (247–276), P?<?0.0001] than the TI-scout-based TI₀, resulting in a TI₀?~?20 ms shorter than what was obtained by IR_synth (P?=?0.0156). In the MOLLI group (n?=?63), IR_synth-based TI₀ was significantly longer than the TI-scout-based TI₀ [298 ms (262–334) vs. 242 ms (217–267), P?=?0.0313]. The quality of myocardial nulling was rated higher [2.4 (2.2–2.5) vs. 2.0 (1.8–2.1), P?=?0.0042] and the remote/background SIR was found to be more optimal (1.6 [1.1–2.1] vs. 2.6 [1.8–3.3], P?=?0.0256) in the MOLLI group. T1-based IR_synth selects TI₀ for LGE more accurately than conventional TI-scout imaging. IR_synth improves TI₀ selection by providing excellent visualization of the representative image contrast for LGE images, reducing operator dependence in LGE acquisition.     

Cumulative mechanisms of lymphoid tissue fibrosis and T cell depletion in HIV-1 and SIV infections

The hallmark of HIV-1 and SIV infections is CD4(+) T cell depletion. Both direct cell killing and indirect mechanisms related to immune activation have been suggested to cause the depletion of T cells. We have now identified a mechanism by which immune activation-induced fibrosis of lymphoid tissues leads to depletion of naive T cells in HIV-1 infected patients and SIV-infected rhesus macaques. The T regulatory cell response to immune activation increased procollagen production and subsequent deposition as fibrils via the TGF-β1 signaling pathway and chitinase 3-like-1 activity in fibroblasts in lymphoid tissues from patients infected with HIV-1. Collagen deposition restricted T cell access to the survival factor IL-7 on the fibroblastic reticular cell (FRC) network, resulting in apoptosis and depletion of T cells, which, in turn, removed a major source of lymphotoxin-β, a survival factor for FRCs during SIV infection in rhesus macaques. The resulting loss of FRCs and the loss of IL-7 produced by FRCs may thus perpetuate a vicious cycle of depletion of T cells and the FRC network. Because this process is cumulative, early treatment and antifibrotic therapies may offer approaches to moderate T cell depletion and improve immune reconstitution during HIV-1 infection.     

Comparison of quantitative imaging parameters using cardiovascular magnetic resonance between cardiac amyloidosis and hypertrophic cardiomyopathy: inversion time scout versus T1 mapping

To compare inversion time (TI) parameters, native T1, and extracellular volume (ECV) on cardiac magnetic resonance (CMR) imaging between patients with cardiac amyloidosis (CA) or hypertrophic cardiomyopathy (HCMP). Forty six patients with biopsy-confirmed CA and 30 patients with HCMP who underwent CMR were included. T1 and TI values were measured in the septum and cavity of the left ventricle on T1 mapping and TI scout images. TI values were selected at nulling point for each myocardium and blood pool. Native T1, ECV, and TI interval values were significantly different between the CA (1170.5?±?86.4 ms, 56.7?±?12.2, ? 11.5?±?28.4 ms) and HCMP (1059.5?±?63.4 ms, 28.5?±?5.8, 66.2?±?25.4 ms) (all p?<?0.001). The diagnostic performance of the TI interval (area under the ROC curve, 0.975) was not inferior to that of the ECV (0.980, p?=?0.776), and it was superior to that of the native T1 (0.845, p?=?0.004). The diagnostic performance of TI interval was comparable to that of ECV for differential diagnosis between CA and HCMP. TI interval showed the feasibility as quantitative CMR parameter when T1 mapping images are not available.     

Mapping of arable land in Russia using multi-year time series of MODIS data and the LAGMA classification technique

The sustainable agriculture requires a regular country-wide update of information on the status and extension of arable land in Russia. The arable land mapping method is developed based on multi-year time series of Moderate Resolution Imaging Spectroradiometer (MODIS) data. The method exploits differences between the intra- and inter-annual changes in the spectral reflectance of arable land and the corresponding changes for other land cover types. It involves a set of satellite data-derived phenological metrics generated using a 6 years long time series of the perpendicular vegetation index (PVI). The approach utilizes the Locally Adaptive Global Mapping Algorithm (LAGMA), which is a supervised classification technique accounting for the spatial variability of intra-classes spectral properties. The method has been applied to produce a uniform time series of comparable annual arable land maps for Russia at 250 m spatial resolution for the years 2005–2013. Countrywide arable land area trends over the above time series were found to be consistent with official statistics (ROSSTAT).The mapping result has been evaluated using reference data providing F-score exceeding 80% for the most productive regions.