SUMMARY:Resting-state fMRI was first described by Biswal et al in 1995 and has since then been widely used in both healthy subjects and patients with various neurologic, neurosurgical, and psychiatric disorders. As opposed to paradigm-or task-based functional MR imaging, resting-state fMRI does not require subjects to perform any specific task. The low-frequency oscillations of the resting-state fMRI signal have been shown to relate to the spontaneous neural activity. There are many ways to analyze resting-state fMRI data. In this review article, we will briefly describe a few of these and highlight the advantages and limitations of each. This description is to facilitate the adoption and use of resting-state fMRI in the clinical setting, helping neuroradiologists become familiar with these techniques and applying them for the care of patients with neurologic and psychiatric diseases.ABBREVIATIONS: ALFF ϭ Amplitude of Low Frequency Fluctuations; BOLD ϭ blood oxygen level-dependent; FCD ϭ functional connectivity density; ICA ϭ

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A bdominal aortic aneurysms (AAAs), characterized by a permanent, localized dilatation (ballooning) of the abdominal aorta that exceeds the normal diameter by >50%, are the most common form of aortic aneurysm. AAA rupture and the associated catastrophic physiological insult carry an overall mortality rate in excess of 80%; ruptured AAAs are the 13th leading cause of death in the United States.1,2 Pathologically, AAAs are characterized by increased inflammatory cell infiltration, aberrant oxidant stress, medial elastin degradation, and medial collagen deposition. Apart from surgery, few medical treatments have been shown to prevent AAA development and growth, 3,4 primarily as a result of the limited understanding of its pathogenic mechanisms.AAAs are found in up to 8% of men aged >65 years. AAA incidence increases steeply by 40% every 5 years in men who Molecular Medicine© 2016 American Heart Association, Inc. Rationale: Uncontrolled growth of abdominal aortic aneurysms (AAAs) is a life-threatening vascular disease without an effective pharmaceutical treatment. AAA incidence dramatically increases with advancing age in men. However, the molecular mechanisms by which aging predisposes individuals to AAAs remain unknown.Objective: In this study, we investigated the role of SIRT1 (Sirtuin 1), a class III histone deacetylase, in AAA formation and the underlying mechanisms linking vascular senescence and inflammation. Methods and Results:The expression and activity of SIRT1 were significantly decreased in human AAA samples.SIRT1 in vascular smooth muscle cells was remarkably downregulated in the suprarenal aortas of aged mice, in which AAAs induced by angiotensin II infusion were significantly elevated. Moreover, vascular smooth muscle cell-specific knockout of SIRT1 accelerated angiotensin II-induced formation and rupture of AAAs and AAArelated pathological changes, whereas vascular smooth muscle cell-specific overexpression of SIRT1 suppressed angiotensin II-induced AAA formation and progression in Apoe −/− mice. Furthermore, the inhibitory effect of SIRT1 on AAA formation was also proved in a calcium chloride (CaCl 2 )-induced AAA model. Mechanistically, the reduction of SIRT1 was shown to increase vascular cell senescence and upregulate p21 expression, as well as enhance vascular inflammation. Notably, inhibition of p21-dependent vascular cell senescence by SIRT1 blocked angiotensin II-induced nuclear factor-κB binding on the promoter of monocyte chemoattractant protein-1 and inhibited its expression. Chen et al Conclusions: SIRT1 Reduction Promotes AAAs 1077are >65 years old, indicating that age is a major risk factor for AAAs.2 Although age-related alterations such as enhanced inflammatory responses, vascular stiffening, and oxidative stress make aged arteries more susceptible to vascular diseases, such as atherosclerosis, 5-7 the reasons why AAAs are often observed in patients with advanced age (>65 years) and how advanced age dramatically accelerates the development and progression of aneurysms in abdominal ...

3 J. MAGN. RESON. IMAGING 2017;45:1798-1808.

Arterial stiffness is an independent risk factor for stroke and myocardial infarction. This study was designed to investigate the role of SIRT1, an important deacetylase, and its relationship with Klotho, a kidney-derived aging-suppressor protein, in the pathogenesis of arterial stiffness and hypertension. We found that the serum level of Klotho was decreased by nearly 45% in patients with arterial stiffness and hypertension. Interestingly, Klotho haplodeficiency caused arterial stiffening and hypertension, as evidenced by significant increases in pulse wave velocity (PWV) and blood pressure (BP) in Klotho-haplodeficient (KL+/−) mice. Notably, the expression and activity of SIRT1 were decreased significantly in aortic endothelial and smooth muscle cells in KL+/− mice, suggesting that Klotho deficiency downregulates SIRT1. Treatment with SRT1720 (15 mg/kg/day, IP), a specific SIRT1 activator, abolished Klotho deficiency-induced arterial stiffness and hypertension in KL+/− mice. Klotho deficiency was associated with significant decreases in activities of AMP-activated protein kinase alpha (AMPKα) and endothelial nitric oxide synthase (eNOS) in aortas, which were abolished by SRT1720. Furthermore, Klotho deficiency upregulated NADPH oxidase activity and superoxide production, increased collagen expression, and enhanced elastin fragmentation in the media of aortas. These Klotho deficiency-associated changes were blocked by SRT1720. In conclusion, this study provides the first evidence that Klotho deficiency downregulates SIRT1 activity in arterial endothelial and smooth muscle cells. Pharmacological activation of SIRT1 may be an effective therapeutic strategy for arterial stiffness and hypertension.

Neutrophil gelatinase-associated lipocalin (NGAL) has been identified as one of the most sensitive and specific biomarkers for predicting cardiac surgery-associated acute kidney injury (CSA-AKI); however, variable performance characteristics have been reported. We therefore performed a diagnostic meta-analysis to investigate the diagnostic accuracy of NGAL in early (within 12 h postoperatively) diagnosis of CSA-AKI using established guidelines. The search was carried out electronically with Medline (through PubMed interface), Embase, Cochrane library, ISI Web of Science, Scopus and ClinicalTrials.gov (up to 5 September 2014), and hand-searching was also done. Two reviewers conducted study inclusion, data extractions and quality assessment of the studies independently. The diagnostic capacity of NGAL for CSA-AKI was assessed using pooled sensitivity and specificity, diagnostic odds ratio (DOR), area under the summary receiver operating characteristic curve (AUC). Meta-Disc 1.4 and STATA 12.0 were used to investigate the source of heterogeneity and to perform the meta-analysis. Twenty-four studies (33 data sets of 4066 patients) were considered, which were all of good methodological quality. The overall pooled sensitivity of NGAL for the diagnosis of AKI was 0.68 [95% confidence interval (CI), 0.65-0.70], and specificity was 0.79 (95% CI, 0.77-0.80). The overall pooled positive likelihood ratio and negative likelihood ratio were 3.98 (95% CI, 3.05-5.20) and 0.33 (95% CI, 0.24-0.45), respectively, with a DOR of 13.05 (95% CI, 7.85-21.70). The receiver operating characteristic analysis showed an AUC [standard error (SE)] of 0.86 (0.02) and with a Q*-value (SE) of 0.79 (0.02). Subgroup analysis showed that NGAL had better predictive ability in neonates/children compared with adults (DOR, 19.37; AUC, 0.89 vs DOR, 8.98; AUC, 0.83), and adults without pre-existing renal insufficiency (PRI) had higher diagnostic value than adults without PRI to predict CSA-AKI (DOR, 15.43; AUC, 0.87 vs DOR, 6.56; AUC, 0.81). Both plasma/serum and urine NGAL had the highly predictive nature for early diagnosis of CSA-AKI (DOR, 13.09; AUC, 0.85 vs DOR, 13.20; AUC, 0.88), while lower DOR and AUC values were shown (DOR, 8.31; AUC, 0.81) when measured using standardized clinical platforms, compared with research-based assays (DOR, 19.22; AUC, 0.89). I(2)-values showed substantial heterogeneity, which mainly stems from characteristics of patient population (P = 0.037). NGAL diagnostic accuracy in early detection of CSA-AKI is high, especially in neonates/children or adults with normal baseline renal function.

Klotho (KL) is a newly discovered aging suppressor gene. In mice, the KL gene extends the lifespan when overexpressed and shortens the lifespan when disrupted. This study investigated if KL deficiency affects BP and salt sensitivity using KL mutant heterozygous (+/2) mice and wild-type (WT) mice (9 weeks of age, 16 mice per group). Notably, systolic BP in KL(+/2) mice began to increase at the age of 15 weeks, reached a peak level at the age of 17 weeks, and remained elevated thereafter, whereas systolic BP remained consistent in WT mice. High salt (HS) intake further increased BP in KL(+/2) mice but did not affect BP in WT mice. Blockade of CC chemokine receptor 2 (CCR2), involved in monocyte chemotaxis, by a specific CCR2 antagonist (INCB3284) abolished the HS-induced increase in BP in KL(+/2) mice. Furthermore, HS loading substantially increased the expression of monocyte chemotactic protein-1 and the infiltration of macrophages and T cells in kidneys in KL(+/2) mice, and treatment with INCB3284 abolished these effects. Treatment of KL(+/2) mice with INCB3284 also attenuated the increased renal expressions of serum glucocorticoid-regulated kinase 1, thiazide-sensitive NaCl cotransporter, and ATP synthase b along with the renal structural damage and functional impairment induced by HS loading. In conclusion, KL deficiency caused salt-sensitive hypertension and renal damage by CCR2-mediated inflammation. In 1997, a new aging suppressor gene was identified and named after the purported Greek Moira Klotho, 1 who spins the thread of life and controls the ultimate destiny of humans. Insertional mutation of mouse klotho gene resulted in extensive premature aging phenotypes and shortens lifespan. 1 However, overexpression of mouse klotho gene extended the lifespan by 20%-30% and rescued aging disorders. 2 Therefore, klotho is an antiaging gene.Aging is characterized by age-related deterioration in health. Hypertension is a common agingrelated disorder. The prevalence of hypertension increases with age. 3 On the basis of an epidemiologic study, 3 the prevalence of hypertension is more than doubled in the elderly than the young population. More than two thirds of individuals over age 65 years suffer from hypertension according to the Seventh Report of the Joint National Committee. 4 Salt intake is one of the main environmental factors contributing to the development of hypertension. An increase in salt sensitivity has been noted with advancing age in numerous studies. 5-9 Salt sensitivity is more common in the old than the young population. The relationship of age and salt sensitivity seems to be stronger in hypertensive than

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