Search

Hong Jiang,1,2 Ava-Gaye Simms,1 Shokufeh Sadaghiani,3 Yu You Jiang,4 Jessica IW Morgan,4 Geoffrey K Aguirre,3 Pradip M Pattany,5 John A Detre,2 Jianhua Wang1 1Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, FL, USA; 2Department of Neurology, University of Miami Miller School of Medicine, Miami, FL, USA; 3Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 4Scheie Eye Institute and Center for Advanced Retinal and Ocular Therapeutics, Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA; 5Department of Radiology, University of Miami Miller School of Medicine, Miami, FL, USACorrespondence: Jianhua Wang, Bascom Palmer Eye Institute, University of Miami, Miller School of Medicine, 1638 NW 10th Avenue, McKnight Building - Room 202A, Miami, FL, 33136, USA, Tel +1 305 482-5010, Fax +1 305 482-5012, Email jwang3@med.miami.eduBackground/Aims: This study was to determine the test–retest repeatability in quantifying macular capillary perfusion density (CPD, expressed as fractal dimension) using optical coherence tomography angiography (OCTA) in a multi-center setting.Methods: OCTA data were obtained in self-reported healthy subjects from Bascom Palmer Eye Institute at the University of Miami (UM, N = 18) and the University of Pennsylvania (UPenn, N = 22). The right eye of each subject was imaged twice at the first visit and then again at an interval of one week to assess intra-visit and inter-visit repeatability. The macular area of the OCTA-derived capillary perfusion density (OCTA-CPD) was analyzed by custom-made image processing and fractal analysis software. Fractal analysis was performed on the skeletonized microvascular network to yield OCTA-CPD by box-counting to the fractal dimension (Dbox) in the superficial vascular plexus (SVP). Repeatability was assessed by three measures: within-subject standard deviation (Sw), coefficient of variation (CoV) of repeated measures, and intraclass correlation coefficient (ICC).Results: OCTA-CPD from both sites (UM and UPENN) showed good to excellent intra-visit repeatability, as demonstrated by the Sw ≤ 0.004, CoVs ≤ 0.23%, and ICCs ≥ 0.61. Similarly, both sites had good to excellent inter-visit repeatability, as shown by the Sw ≤ 0.005, CoVs ≤ 0.28%, and ICCs ≥ 0.61. The Bland-Altman plots of the intra-visit and inter-visit measurements showed excellent agreements between the paired measurements with minimal biases.Conclusion: Our data showed that comparable high repeatability of OCTA-CPD can be achieved in both research sites using the same device, scan protocol, and image analysis.Keywords: retinal capillary perfusion density, optical coherence tomography angiography, repeatability, multi-center study

The present study examined the pathogenesis of interstitial inflammation and fibrosis in antihypertensively treated rats with two-kidney, one-clip hypertension. Hypertensive rats were randomized into four groups: no treatment and moderate, intermediate, and intensified lowering of blood pressure with increasing doses of a vasopeptidase inhibitor for 6 wk. The vasopeptidase inhibitor dose dependently lowered blood pressure. The tubulointerstitial damage was accompanied by a diffuse infiltration of mononuclear cells and circumscript mononuclear inflammatory cell cluster formation consisting mainly of T cells and to a lesser degree of macrophages and B cells. Real-time PCR analyses showed a dose-dependent induction of MCP-1 and the Th1-type chemokines IP10 and Mig as well as their receptor CXCR3 and the Th1 cytokine IFN-[gamma]. In situ hybridization and laser microdissection revealed a strong expression of these Th1-associated transcripts in the clusters and, in the case of MCP-1, also diffusely in the interstitium. The inflammation was accompanied by the appearance of myofibroblasts and synthesis of the fibrogenic factor plasminogen activator inhibitor-1 as well as the collagenase matrix metalloproteinase-2, leading to collagen I upregulation and interstitial scarring. No inflammation or fibrosis was found in normotensive rats treated with the vasopeptidase inhibitor. The renal injury in the clipped kidney is accompanied by compartment-specific chemokine expression and cell cluster formation of Th1 specificity associated with upregulation of fibrogenic proteins and matrix metalloproteinases. These findings suggest that the Th1 chemokines IP10 and Mig as well as their receptor CXCR3 are potential targets for therapeutic interventions in ischemic nephropathy. vasopeptidase inhibition; chemokines; Th1 response; acute renal failure; matrix metalloproteinases; MCP-1; IP10; Mig; renovascular hypertension

Scaling temporal dynamics in functional MRI (fMRI) signals have been evidenced for a decade as intrinsic characteristics of ongoing brain activity (Zarahn et al., 1997). Recently, scaling properties were shown to fluctuate across brain networks and to be modulated between rest and task (He, 2011): notably, Hurst exponent, quantifying long memory, decreases under task in activating and deactivating brain regions. In most cases, such results were obtained: First, from univariate (voxelwise or regionwise) analysis, hence focusing on specific cognitive systems such as Resting-State Networks (RSNs) and raising the issue of the specificity of this scale-free dynamics modulation in RSNs. Second, using analysis tools designed to measure a single scaling exponent related to the second order statistics of the data, thus relying on models that either implicitly or explicitly assume Gaussianity and (asymptotic) self-similarity, while fMRI signals may significantly depart from those either of those two assumptions (Ciuciu et al., 2008; Wink et al., 2008). To address these issues, the present contribution elaborates on the analysis of the scaling properties of fMRI temporal dynamics by proposing two significant variations. First, scaling properties are technically investigated using the recently introduced Wavelet Leader-based Multifractal formalism (WLMF; Wendt et al., 2007). This measures a collection of scaling exponents, thus enables a richer and more versatile description of scale invariance (beyond correlation and Gaussianity), referred to as multifractality. Also, it benefits from improved estimation performance compared to tools previously used in the literature. Second, scaling properties are investigated in both RSN and non-RSN structures (e.g., artifacts), at a broader spatial scale than the voxel one, using a multivariate approach, namely the Multi-Subject Dictionary Learning (MSDL) algorithm (Varoquaux et al., 2011) that produces a set of spatial components that appear more sparse than their Independent Component Analysis (ICA) counterpart. These tools are combined and applied to a fMRI dataset comprising 12 subjects with resting-state and activation runs (Sadaghiani et al., 2009). Results stemming from those analysis confirm the already reported task-related decrease of long memory in functional networks, but also show that it occurs in artifacts, thus making this feature not specific to functional networks. Further, results indicate that most fMRI signals appear multifractal at rest except in non-cortical regions. Task-related modulation of multifractality appears only significant in functional networks and thus can be considered as the key property disentangling functional networks from artifacts. These finding are discussed in the light of the recent literature reporting scaling dynamics of EEG microstate sequences at rest and addressing non-stationarity issues in temporally independent fMRI modes. [ABSTRACT FROM AUTHOR]

Scale-free (or 1/f spectral) properties in functional MRI (fMRI) signals have been evidenced for a decade as intrinsic characteristics of ongoing brain activity [70]. Recently, they were shown to fluctuate across brain networks and to be modulated between rest and task [37]: Notably, Hurst exponent, quantifying long memory, decreases during task in activating and deactivating brain regions. Such results were obtained using tools assuming Gaussianity and self-similar models, while fMRI signals may significantly depart from those two assumptions [24] and were often based on voxelwise or regionwise independent analysis, hence showing large inter-subject variability. The present article aims at contributing to the analysis of temporal scale-free properties of fMRI signals in two respects. First, a recent statistical analysis tool, the Wavelet Leader-based Multifractal formalism (WLMF), is used [68, 3]. It shows improved estimation performance, and it is framed within a rich and versatile class of models, that of multifractal processes. Second, scalefree properties are not investigated at the voxel or region scale. Instead, resting-state brain networks are extracted using a Multi- Subject Dictionary Learning (MSDL) algorithm [63]: It produces both a set of spatial components, and a set of times series, for each component and each subject, that conveys ongoing dynamics in functional networks but also in artifacts. These combined tools are applied to an fMRI dataset comprising 12-subjects with resting-state and activation runs [55]. This dataset enabled us to confirm the task-related decrease of long memory in functional networks but also in artifacts making this feature not specific to functional networks. Also, most of fMRI signals appear multifractal at rest except in non-cortical regions. Task-related modulation of multifractality appears only significant in functional networks and thus can be considered the key property to disentangle functional networks from artifacts. Our results are finally discussed in the light of the recent literature dealing with i) the scale-free dynamics of EEG microstate sequences at rest and ii) non-stationarities in temporally independent fMRI modes. [ABSTRACT FROM AUTHOR]

Recently, a (pro)renin receptor has been identified which mediates profibrotic effects independent of angiotensin II. Because antihypertensive therapy induces renal injury in the clipped kidney of two kidney-1-clip hypertensive rats, we examined the regulation of renin and the (pro)renin receptor in this model. Hypertensive Goldblatt rats were treated with increasing doses of the vasopeptidase inhibitor AVE 7688 after which the plasma renin and prorenin as well as the renal renin and (pro)renin receptor expression were measured. The vasopeptidase inhibitor dose-dependently lowered blood pressure, which was associated with a massive increase in plasma prorenin and renin as well as increased renal renin expression. The (pro)renin receptor was upregulated in the clipped kidney of the Goldblatt rat indicating a parallel upregulation of renin and its receptor in vivo. Immunohistochemistry showed a redistribution of renin upstream from the glomerulus in preglomerular vessels and renin staining in tubular cells. Expression of the (pro)renin receptor was increased in the vessels and tubules. This upregulation was associated with thickening of renin-positive vessels and tubulointerstitial damage. We propose that renin and the (pro)renin receptor may play a profibrotic role in the clipped kidney of Goldblatt rats treated for hypertension.Kidney International (2007) 72, 725–730; doi:10.1038/sj.ki.5002408; published online 27 June 2007 [ABSTRACT FROM AUTHOR]