Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease.
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ABSTRACT: Purpose
To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method.Materials and methods
79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acoustic power contrast-specific imaging was used for quantitative analysis.Results
Normal controls (NCs) had the highest levels of AUC, AUC1, and AUC2. Compared to the normal SUA DKD group, high SUA DKD patients had significantly higher IMAX, AUC, and AUC1 (P < 0.05). DKD patients with low urinary uric acid (UUA) excretion had significantly higher AUC2 compared to DKD patients with normal UUA (P < 0.05).Conclusion
Hyperuricemia in DKD patients was associated with a renal ultrasound image suggestive of microvascular hyperperfusion. The CEUS parameter AUC1 holds promise as an indicator for renal microvascular hyperperfusion, while AUC2 might be a useful indicator of declining glomerular filtration rate in DKD patients with decreased excretion of uric acid.
SUBMITTER: Wang L
PROVIDER: S-EPMC4464846 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
Publications
Use of Contrast-Enhanced Ultrasound to Study Relationship between Serum Uric Acid and Renal Microvascular Perfusion in Diabetic Kidney Disease.
Wang Ling L Cheng Jia-Fen JF Sun Li-Ping LP Song Ya-Xiang YX Guo Le-Hang LH Xu Jun-Mei JM Wu Tian-Fu TF Mohan Chandra C Peng Ai A Xu Hui-Xiong HX Liu Xin-Ying XY
BioMed research international 20150526
<h4>Purpose</h4>To investigate the relationship between uric acid and renal microvascular perfusion in diabetic kidney disease (DKD) using contrast-enhanced ultrasound (CEUS) method.<h4>Materials and methods</h4>79 DKD patients and 26 healthy volunteers were enrolled. Renal function and urine protein markers were tested. DKD patients were subdivided into two groups including a normal serum uric acid (SUA) group and a high SUA group. Contrast-enhanced ultrasound (CEUS) was performed, and low acou ...[more]
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Project description:BackgroundIndividuals with chronic kidney disease (CKD) have decreased kidney cortical microvascular perfusion, which may lead to worsening kidney function over time, but methods to quantify kidney cortical microvascular perfusion are not feasible to incorporate into clinical practice. Contrast-enhanced ultrasound (CEUS) may quantify kidney cortical microvascular perfusion, which requires further investigation in individuals across the spectrum of kidney function.MethodsWe performed CEUS on a native kidney of 83 individuals across the spectrum of kidney function and calculated quantitative CEUS-derived kidney cortical microvascular perfusion biomarkers. Participants had a continuous infusion of the microbubble contrast agent (Definity) with a flash-replenishment sequence during their CEUS scan. Lower values of the microbubble velocity (β) and perfusion index (β×A) may represent lower kidney cortical microvascular perfusion. Multivariable linear regression models tested the associations of the microbubble velocity (β) and perfusion index (β×A) with estimated glomerular filtration rate (eGFR).ResultsThirty-eight individuals with CKD (mean age±SD 65.2±12.6 years, median [IQR] eGFR 31.5 [18.9-41.5] ml/min per 1.73 m2), 37 individuals with end stage kidney disease (ESKD; age 54.8±12.3 years), and eight healthy volunteers (age 44.1±15.0 years, eGFR 117 [106-120] ml/min per 1.73 m2) underwent CEUS without side effects. Individuals with ESKD had the lowest microbubble velocity (β) and perfusion index (β×A) compared with individuals with CKD and healthy volunteers. The microbubble velocity (β) and perfusion index (β×A) had moderate positive correlations with eGFR (β: r s=0.44, P<0.001; β×A: r s=0.50, P<0.001). After multivariable adjustment, microbubble velocity (β) and perfusion index (β×A) remained significantly associated with eGFR (change in natural log transformed eGFR per 1 unit increase in natural log transformed biomarker: β, 0.38 [95%, CI 0.17 to 0.59]; β×A, 0.79 [95% CI, 0.45 to 1.13]).ConclusionsCEUS-derived kidney cortical microvascular perfusion biomarkers are associated with eGFR. Future studies are needed to determine if CEUS-derived kidney cortical microvascular perfusion biomarkers have prognostic value.
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Project description:The ability to accurately evaluate skeletal muscle microvascular blood flow has broad clinical applications for understanding the regulation of skeletal muscle perfusion in health and disease states. Contrast-enhanced ultrasound (CEU) perfusion imaging, a technique originally developed to evaluate myocardial perfusion, is one of many techniques that have been applied to evaluate skeletal muscle perfusion. Among the advantages of CEU perfusion imaging of skeletal muscle is that it is rapid, safe and performed with equipment already present in most vascular medicine laboratories. The aim of this review is to discuss the use of CEU perfusion imaging in skeletal muscle. This article provides details of the protocols for CEU imaging in skeletal muscle, including two predominant methods for bolus and continuous infusion destruction-replenishment techniques. The importance of stress perfusion imaging will be highlighted, including a discussion of the methods used to produce hyperemic skeletal muscle blood flow. A broad overview of the disease states that have been studied in humans using CEU perfusion imaging of skeletal muscle will be presented including: (1) peripheral arterial disease; (2) sickle cell disease; (3) diabetes; and (4) heart failure. Finally, future applications of CEU imaging in skeletal muscle including therapeutic CEU imaging will be discussed along with technological developments needed to advance the field.
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Project description:(1) Background: The renal microcirculation is essential to maintain the renal function, but its determinants in humans have been poorly studied. Contrast-enhanced ultrasound (CEUS) allows the non-invasive quantification of the cortical micro-perfusion at the bedside using the perfusion index (PI). The aims of this study were to assess whether differences exist in PI between healthy males and females and to identify clinical determinants associated with cortical micro-perfusion. (2) Methods: Healthy, normotensive volunteers (eGFR > 60 mL/min/1.73 m2, no albuminuria) underwent CEUS under standardized conditions with the destruction-reperfusion (DR) technique. The mean PI of four DR sequences was reported as the primary outcome measure (3) Results: A total of 115 subjects (77 females and 38 males) completed the study; the mean ± SD age was, respectively, 37.1 ± 12.2 and 37.1 ± 12.7 years in females and males, and the mean eGFR was 105.9 ± 15.1 and 91.0 ± 17.4 mL/min/1.73 m2. The PI (median) was higher in females than in males, i.e., 2705 (IQR 1641-3777) vs. 1965 (IQR 1294-3346) arbitrary units (a.u), p = 0.02). A correlation analysis showed positive associations between PI and eGFR, female sex, heart rate, plasma renin activity (PRA) and plasma aldosterone concentrations (PAC), negative associations with potassium, bicarbonate and systolic blood pressure, and no associations with age, body mass index and renal resistive index (RRI). In a multivariate linear regression analysis, only PRA remained significantly associated with PI. (4) Conclusions: Although the PI was higher among females, this association was no longer significant after adjustment for covariates. There was no difference in females tested during the follicular or the luteal phases. In conclusion, the PI was only weakly influenced by classic clinical variables, but was positively associated with PRA, suggesting that the renin-angiotensin system plays a role in the regulation of the cortical micro-perfusion in humans. Identifying which other factors contribute to the large variations in micro-perfusion across individuals needs further study.
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Project description:BackgroundDiabetic nephropathy (DN) is a common chronic microvascular complication of diabetes. Noninvasive diagnosis of DN is difficult. Contrast-enhanced ultrasound (CEUS), as a functional imaging method, provides noninvasive real-time images and quantitative assessment of renal microvascular perfusion. This study investigated the efficacy of CEUS in discriminating between DN and normal kidneys in rhesus monkeys.MethodsA total of 12 male rhesus monkeys (DN model group, n=6; normal control group, n=6) were included in this study. The following parameters were evaluated: (I) blood biochemistry; (II) CEUS; and (III) ultrasound-guided renal biopsy.ResultsPathological and biochemical results showed that all subjects in the lesion group had serious renal damage. There were significant differences in the CEUS parameters, including the area under the curve, the time from peak to one half, and peak intensity between the lesion group and the normal group. The time to peak was slightly delayed in the lesion group. There was no significant difference in the rise time between the two groups.ConclusionsAlthough the precise CEUS parameters that may best predict renal damage still require systematic evaluation, the results of these animal studies suggest that CEUS may be used as a supplemental tool in diagnosing renal damage in rhesus monkeys with DN. We hope these findings can provide insights for the application of CEUS in DN.
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Project description:Contrast-enhanced ultrasound (CEUS) is an emerging technique to evaluate tissue perfusion. Promising results have been obtained in the evaluation of renal perfusion in health and disease, both in human and veterinary medicine. Renal scintigraphy using 99mTc-Mercaptoacetyltriglycine (MAG3) is another non-invasive technique that can be used to evaluate renal perfusion. However, no data are available on the ability of CEUS or 99mTc- MAG3 scintigraphy to detect small changes in renal perfusion in cats. Therefore, both techniques were applied in a normal feline population to evaluate detection possibilities of perfusion changes by angiotensin II (AT II). Contrast-enhanced ultrasound using a bolus injection of commercially available contrast agent and renal scintigraphy using 99mTc-MAG3 were performed in 11 healthy cats after infusion of 0,9% NaCl (control) and AT II. Angiotensin II induced changes were noticed on several CEUS parameters. Mean peak enhancement, wash-in perfusion index and wash-out rate for the entire kidney decreased significantly after AT II infusion. Moreover, a tendency towards a lower wash-in area-under-the curve was present. Renal scintigraphy could not detect perfusion changes induced by AT II. This study shows that CEUS is able to detect changes in feline renal perfusion induced by AT II infusion.
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Project description:New findingsWhat is the central question of this study? Contrast-enhanced ultrasound (CEUS) can be used to directly assess skeletal muscle perfusion but its day-to-day repeatability over time has not yet been validated: is CEUS a repeatable method for the measurement of skeletal muscle microvascular blood flow (MBF) at rest and in response to exercise, across independent assessment sessions? What is the main finding and its importance? A strong agreement between CEUS MBF measures across sessions suggests it is a repeatable method for assessing skeletal muscle perfusion over time. This validation provides confidence for incorporating these measures into longitudinal studies such as a chronic intervention or disease progression to gain further knowledge of skeletal muscle microvascular function.AbstractContrast-enhanced ultrasound (CEUS) can be used to directly assess skeletal muscle perfusion. However, its repeatability over time has not yet been validated and therefore its use in longitudinal measures (i.e., exploring the impact of a chronic intervention or disease progression) is limited. This study aimed to determine the repeatability of CEUS for the measurement of skeletal muscle microvascular blood flow (MBF) at baseline and in response to exercise, across independent assessment sessions. Ten healthy volunteers (five female; 30 ± 6 years) had CEUS of the right vastus lateralis recorded in two separate sessions, 14 days apart. Measurements were taken at baseline, during an isometric leg extension and during recovery. Acoustic intensity data from a region of interest were plotted as a replenishment curve to obtain blood volume (A) and flow velocity (β) values from a one-phase association non-linear regression of mean tissue echogenicity. Linear regression and Bland-Altman analyses of A and β values were performed, with significance assumed as P < 0.05. Strong positive correlations were observed across sessions for all A and β values (both P < 0.0001). Bland-Altman analysis showed a bias (SD) of -0.013 ± 1.24 for A and -0.014 ± 0.31 for β. A bias of 0.201 ± 0.770 at baseline, 0.527 ± 1.29 during contraction and -0.203 ± 1.29 at recovery was observed for A, and -0.0328 ± 0.0853 (baseline), -0.0446 ± 0.206 (contraction) and 0.0382 ± 0.233 (recovery) for β. A strong agreement between CEUS MBF measures across independent sessions suggests it to be a repeatable method for assessing skeletal muscle perfusion over time, and therefore facilitates wider use in longitudinal studies.
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Project description:PurposeContrast-enhanced ultrasound imaging has expanded the diagnostic potential of ultrasound by enabling real-time imaging and quantification of tissue perfusion. Several perfusion models and curve fitting methods have been developed to quantify the temporal behavior of tracer signal and standardize perfusion quantification. While the least-squares approach has traditionally been applied for curve fitting, it can be inadequate for noisy and complex data. Moreover, previous research suggests that certain perfusion models may be more relevant depending on the organ or tissue imaged. We propose a multi-model framework to select the most appropriate perfusion model and curve fitting method for each diagnostic application.MethodsOur multi-model approach uses a system identification method, which estimates perfusion parameters from the model with the best fit to a given time-intensity curve. We compared current perfusion quantification methods that use a single perfusion model and curve fitting method and our proposed multi-model framework on bolus 3D dynamic contrast-enhanced ultrasound (DCE-US) in vivo images obtained in mice implanted with a colon cancer, as well as on simulation data. The quality of fit in estimating perfusion parameters was evaluated using the Spearman correlation coefficient, the coefficient of determination (R2 ), and the normalized root-mean-square error (NRMSE) to ensure that the multi-model framework finds the best perfusion model and curve fitting algorithm.ResultsOur multi-model framework outperforms conventional single perfusion model approaches with least-squares optimization, providing more robust perfusion parameter estimation. R2 and NRMSE are 0.98 and 0.18, respectively, for our proposed method. By comparison, the performance of the traditional approach is much more dependent upon the selection of the appropriate model. The R2 and NRMSE are 0.91 and 0.31, respectively.ConclusionsThe proposed multi-model framework for perfusion modeling outperforms the current approach of single perfusion modeling using least-squares optimization and more robustly estimates perfusion parameters when using empiric data labeled by an expert as the gold standard. Our technique is minimally sensitive to issues affecting the accuracy of perfusion parameter estimation, including rise time, noise, region of interest size, and frame rate. This framework could be of key utility in modeling different perfusion systems in different tissues and organs.
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Project description:Contrast-enhanced ultrasound (CEUS) enables highly specific time-resolved imaging of vasculature by intravenous injection of ∼2 μm gas filled microbubbles. To develop a quantitative automated diagnosis of breast tumors with CEUS, breast tumors were induced in rats by administration of N-ethyl-N-nitrosourea. A bolus injection of microbubbles was administered and CEUS videos of each tumor were acquired for at least 3 min. The time-intensity curve of each pixel within a region of interest (ROI) was analyzed to measure kinetic parameters associated with the wash-in, peak enhancement, and wash-out phases of microbubble bolus injections since it was expected that the aberrant vascularity of malignant tumors will result in faster and more diverse perfusion kinetics versus those of benign lesions. Parameters were classified using linear discriminant analysis to differentiate between benign and malignant tumors and improve diagnostic accuracy. Preliminary results with a small dataset (10 tumors, 19 videos) show 100% accuracy with fivefold cross-validation testing using as few as two choice variables for training and validation. Several of the parameters which provided the best differentiation between malignant and benign tumors employed comparative analysis of all the pixels in the ROI including enhancement coverage, fractional enhancement coverage times, and the standard deviation of the envelope curve difference normalized to the mean of the peak frame. Analysis of combinations of five variables demonstrated that pixel-by-pixel analysis produced the most robust information for tumor diagnostics and achieved 5 times greater separation of benign and malignant cases than ROI-based analysis.
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Project description:PurposeThe aim of the study was to quantitatively analyze the perfusion characteristics of choroidal metastasis using contrast-enhanced ultrasound (CEUS) and compare its perfusion characteristics with these of choroidal hemangioma and choroidal melanoma.MethodsThe patients who were clinically diagnosed with choroidal metastasis were classified as the study group, and the patients who were diagnosed with choroidal hemangioma and choroidal melanoma during the same period were classified as the comparison group. All patients underwent CEUS examination, and Sonoliver was used to obtain the data on quantitative parameters of the tumor and the adjacent normal orbital tissues, including maximum of intensity (IMAX), rise time (RT), time to peak (TTP), and mean transit time (mTT). Wilcoxon signed rank test was performed to compare the quantitative parameters of choroidal metastasis and normal orbital tissues. Kruskal-Wallis test was adopted to compare the quantitative parameters of the 3 types of tumors, and Bonferroni was used to correct the results of the multiple comparisons. Receiver operating characteristic (ROC) curve analysis was used to identify valuable parameters.ResultsTwenty-six patients (26 eyes) with choroidal metastasis, 55 patients (55 eyes) with choroidal hemangioma, and 49 patients (49 eyes) with choroidal melanoma were enrolled in this study. The IMAX of choroidal metastasis was significantly higher than that of normal orbital tissues, while RT, TTP, and mTT were significantly shorter than these of normal orbital tissues (all p values were <0.001). The IMAX of choroidal metastasis was lower than that of choroidal hemangioma, and RT, TTP, and mTT were shorter than these of choroidal hemangioma and choroidal melanoma (p = 0.002, p = 0.004, p = 0.007). ROC curve analysis showed that areas under the ROC curves (AUCs) of RT and mTT (AUC = 0.851, 95% CI 0.783-0.918 and 0.849, 95% CI 0.783-0.915) were larger.ConclusionQuantitative analysis with CEUS can reflect the perfusion characteristics of choroidal metastasis and can exhibit the difference between its perfusion characteristics and these of choroidal hemangioma and choroidal melanoma. RT and mTT may serve as useful parameters for differentiating choroidal metastasis from choroidal hemangioma and choroidal melanoma.
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Project description:BackgroundThe uteroplacental vascular supply is a critical determinant of placental function and fetal growth. Current methods for the in vivo assessment of placental blood flow are limited.ObjectiveWe demonstrate the feasibility of the use of contrast-enhanced ultrasound imaging to visualize and quantify perfusion kinetics in the intervillous space of the primate placenta.Study designPregnant Japanese macaques were studied at mid second trimester and in the early third trimester. Markers of injury were assessed in placenta samples from animals with or without contrast-enhanced ultrasound exposure (n = 6/group). Human subjects were recruited immediately before scheduled first-trimester pregnancy termination. All studies were performed with maternal intravenous infusion of lipid-shelled octofluoropropane microbubbles with image acquisition with a multipulse contrast-specific algorithm with destruction-replenishment analysis of signal intensity for assessment of perfusion.ResultsIn macaques, the rate of perfusion in the intervillous space was increased with advancing gestation. No evidence of microvascular hemorrhage or acute inflammation was found in placental villous tissue and expression levels of caspase-3, nitrotyrosine and heat shock protein 70 as markers of apoptosis, nitrative, and oxidative stress, respectively, were unchanged by contrast-enhanced ultrasound exposure. In humans, placental perfusion was visualized at 11 weeks gestation, and preliminary data reveal regional differences in intervillous space perfusion within an individual placenta. By electron microscopy, we demonstrate no evidence of ultrastructure damage to the microvilli on the syncytiotrophoblast after first-trimester ultrasound studies.ConclusionsUse of contrast-enhanced ultrasound did not result in placental structural damage and was able to identify intervillous space perfusion rate differences within a placenta. Contrast-enhanced ultrasound imaging may offer a safe clinical tool for the identification of pregnancies that are at risk for vascular insufficiency; early recognition may facilitate intervention and improved pregnancy outcomes.
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