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Comparison of cerebral blood flow measurement with [15O]-water positron emission tomography and arterial spin labeling magnetic resonance imaging: A systematic review.
Fan, AP, Jahanian, H, Holdsworth, SJ, Zaharchuk, G
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2016;(5):842-61
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Abstract
Noninvasive imaging of cerebral blood flow provides critical information to understand normal brain physiology as well as to identify and manage patients with neurological disorders. To date, the reference standard for cerebral blood flow measurements is considered to be positron emission tomography using injection of the [(15)O]-water radiotracer. Although [(15)O]-water has been used to study brain perfusion under normal and pathological conditions, it is not widely used in clinical settings due to the need for an on-site cyclotron, the invasive nature of arterial blood sampling, and experimental complexity. As an alternative, arterial spin labeling is a promising magnetic resonance imaging technique that magnetically labels arterial blood as it flows into the brain to map cerebral blood flow. As arterial spin labeling becomes more widely adopted in research and clinical settings, efforts have sought to standardize the method and validate its cerebral blood flow values against positron emission tomography-based cerebral blood flow measurements. The purpose of this work is to critically review studies that performed both [(15)O]-water positron emission tomography and arterial spin labeling to measure brain perfusion, with the aim of better understanding the accuracy and reproducibility of arterial spin labeling relative to the positron emission tomography reference standard.
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64Cu-DOTATATE for Noninvasive Assessment of Atherosclerosis in Large Arteries and Its Correlation with Risk Factors: Head-to-Head Comparison with 68Ga-DOTATOC in 60 Patients.
Malmberg, C, Ripa, RS, Johnbeck, CB, Knigge, U, Langer, SW, Mortensen, J, Oturai, P, Loft, A, Hag, AM, Kjær, A
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2015;(12):1895-900
Abstract
UNLABELLED The somatostatin receptor subtype 2 is expressed on macrophages, an abundant cell type in the atherosclerotic plaque. Visualization of somatostatin receptor subtype 2, for oncologic purposes, is frequently made using the DOTA-derived somatostatin analogs DOTATOC or DOTATATE for PET. We aimed to compare the uptake of the PET tracers (68)Ga-DOTATOC and (64)Cu-DOTATATE in large arteries, in the assessment of atherosclerosis by noninvasive imaging technique, combining PET and CT. Further, the correlation of uptake and cardiovascular risk factors was investigated. METHODS Sixty consecutive patients with neuroendocrine tumors underwent both (68)Ga-DOTATOC and (64)Cu-DOTATATE PET/CT scans, in random order. For each scan, the maximum and mean standardized uptake values (SUVs) were calculated in 5 arterial segments. In addition, the blood-pool-corrected target-to-background ratio was calculated. Uptake of the tracers was correlated with cardiovascular risk factors collected from medical records. RESULTS We found detectable uptake of both tracers in all arterial segments studied. Uptake of (64)Cu-DOTATATE was significantly higher than (68)Ga-DOTATOC in the vascular regions both when calculated as maximum and mean uptake. There was a significant association between Framingham risk score and the overall maximum uptake of (64)Cu-DOTATATE using SUV (r = 0.4; P = 0.004) as well as target-to-background ratio (r = 0.3; P = 0.04), whereas no association was found with (68)Ga-DOTATOC. The association of risk factors and maximum SUV of (64)Cu-DOTATATE was found driven by body mass index, smoking, diabetes, and coronary calcium score (P < 0.001, P = 0.01, P = 0.005, and P = 0.03, respectively). CONCLUSION In a series of oncologic patients, vascular uptake of (68)Ga-DOTATOC and (64)Cu-DOTATATE was found, with highest uptake of the latter. Uptake of (64)Cu-DOTATATE, but not of (68)Ga-DOTATOC, was correlated with cardiovascular risk factors, suggesting a potential role for (64)Cu-DOTATATE in the assessment of atherosclerosis.
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Transarterial chemoembolization (TACE) plus sorafenib versus TACE for intermediate or advanced stage hepatocellular carcinoma: a meta-analysis.
Zhang, L, Hu, P, Chen, X, Bie, P
PloS one. 2014;(6):e100305
Abstract
BACKGROUND Sorafenib is used in patients with intermediate or advanced stage hepatocellular carcinoma (HCC) before or after of transarterial chemoembolization (TACE). However, the survival outcomes of TACE combined with sorafenib versus TACE alone remain controversial. Thus, we conducted a meta-analysis to evaluate the efficacy and safety of the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC. METHODS Pubmed and Embase databases were systematically reviewed for studies published up to November 2013, that compared TACE alone or in combination with sorafenib. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), time to progression (TTP), objective response rate (ORR), and progression free survival (PFS) using random-effects or fixed-effects model, depending on the heterogeneity between the included studies. RESULTS Six studies published from 2011 to 2013, with a total of 1254 patients, were included in this meta-analysis. The pooled results showed that TACE combined with sorafenib significantly improved OS (HR = 0.65; 95% CI: 0.47-0.89, P = 0.007), TTP (HR = 0.68; 95% CI: 0.52-0.87, P = 0.003), ORR (HR = 1.06; 95% CI: 1.01-1.12, P = 0.021), but did not affect PFS (HR = 0.84; 95% CI: 0.62-1.14, P = 0.267). The incidence of grade III/IV adverse reaction was higher in the TACE plus sorafenib group than in the TACE group. CONCLUSIONS The meta-analysis confirmed that the combination therapy of TACE plus sorafenib in patients with intermediate or advanced stage of HCC, can improve the OS, TTP, and ORR. This combination therapy was also associated with a significantly increased risk of adverse reactions.
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The influence of mean blood pressure on arterial stiffening and endothelial dysfunction in women with rheumatoid arthritis and systemic lupus erythematosus.
Cypienė, A, Dadonienė, J, Rugienė, R, Ryliškytė, L, Kovaitė, M, Petrulionienė, Z, Venalis, A, Laucevičius, A
Medicina (Kaunas, Lithuania). 2010;(8):522-30
Abstract
OBJECTIVE To investigate the carotid-radial pulse wave velocity, augmentation index, and flow-mediated dilation of the brachial artery and factors possibly influencing them in women with rheumatoid arthritis and systemic lupus erythematosus. MATERIAL AND METHODS A total of 63 women with rheumatoid arthritis, 31 with systemic lupus erythematosus, and 72 controls, aged 18-55 years, were examined. Parameters of arterial stiffness, augmentation index and carotid-radial pulse wave velocity, were obtained by applanation tonometry (Sphygmocor (v.7.01) AtCor Medical). Flow-mediated dilatation of the brachial artery, reflecting endothelial function was determined by ultrasound system (Logiq 7, General Electric). RESULTS The groups of women with rheumatoid arthritis and systemic lupus erythematosus lupus differed from controls regarding augmentation index (P<0.001; P=0.008) and did not differ between each other. Women with systemic lupus erythematosus differed from controls regarding pulse wave velocity (P=0.018), while women with rheumatoid arthritis - did not. Flow-mediated dilatation in both the groups of diseases was not different from controls. In rheumatoid arthritis patients, mean blood pressure was the main explanatory factor for augmentation index and pulse wave velocity; vessel diameter and high-density lipoprotein cholesterol - for flow-mediated dilatation. In women with systemic lupus erythematosus, pulse wave velocity was not related to any of the pending parameters; augmentation index was dependent on organ damage index, age, and mean blood pressure, and flow-mediated dilatation on vessel diameter, body mass index, and disease duration. CONCLUSIONS The mean blood pressure was the major and the only one risk factor of arterial stiffening in rheumatoid arthritis, while the disease damage index played the most important role in the systemic lupus erythematosus group. The mean blood pressure in the systemic lupus erythematosus group was not as important as in the rheumatoid arthritis group, though may have a partial influence.
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Hereditary deficiency of gp91(phox) is associated with enhanced arterial dilatation: results of a multicenter study.
Violi, F, Sanguigni, V, Carnevale, R, Plebani, A, Rossi, P, Finocchi, A, Pignata, C, De Mattia, D, Martire, B, Pietrogrande, MC, et al
Circulation. 2009;(16):1616-22
Abstract
BACKGROUND NADPH oxidase is believed to modulate arterial tone, but its role in humans is still unclear. The objective of this study was to evaluate whether NADPH oxidase is involved in flow-mediated arterial dilation (FMD). METHODS AND RESULTS Twenty-five patients with hereditary deficiency of gp91(phox), the catalytic core of NADPH oxidase, (X-CGD), 25 healthy subjects, and 25 obese patients matched for sex and age were recruited. FMD, platelet gp91(phox), serum levels of nitrite and nitrate as markers of nitric oxide generation, oxidized low-density lipoprotein, and urinary excretion of isoprostanes as markers of oxidative stress were determined. Platelet gp91(phox) expression was downregulated in X-CGD patients (1.0+/-0.8 mean fluorescence; P<0.001) and upregulated in obese patients (4.1+/-2.2 mean fluorescence; P=0.01) compared with healthy subjects (2.9+/-1.7 mean fluorescence). Urinary excretion of isoprostanes was reduced in X-CGD patients (41.7+/-33.3 pg/mg creatinine; P=0.04) and increased in obese patients (154.4+/-91 pg/mg creatinine; P<0.001) compared with healthy subjects (69.5+/-52.4 pg/mg creatinine). Obese patients had higher serum oxidized low-density lipoprotein than healthy subjects (35.3+/-6.7 versus 24.8+/-9.8 U/L; P<0.001) and X-CGD patients (28.5+/-7.2 U/L; P<0.001). X-CGD patients had significantly higher FMD (14.7+/-5.9%) compared with healthy subjects (7.9+/-2.5%; P<0.001); obese patients had lower FMD (5.3+/-3.0%; P=0.028) compared with healthy subjects. Serum nitrite and nitrate levels were significantly higher in patients with X-CGD (36.0+/-10.8 micromol/L; P=0.016) and lower in obese patients (9.3+/-11.0 micromol/L; P=0.001) compared with healthy subjects (27.1+/-19.1 micromol/L). Serum nitrite and nitrate levels significantly correlated with FMD (R(s)=0.403, P<0.001) and platelet gp91(phox) (R(s)=-0.515, P<0.001). FMD inversely correlated with platelet gp91(phox) (R(s)=-0.502, P<0.001) and isoprostanes (R(s)=-0.513, P<0.001). CONCLUSIONS This study provides the first evidence that, in humans, gp91(phox) is implicated in the modulation of arterial tone.
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Dual-energy CT discrimination of iodine and calcium: experimental results and implications for lower extremity CT angiography.
Tran, DN, Straka, M, Roos, JE, Napel, S, Fleischmann, D
Academic radiology. 2009;(2):160-71
Abstract
RATIONALE AND OBJECTIVES The purpose of this work was to measure the accuracy of dual-energy computed tomography for identifying iodine and calcium and to determine the effects of calcium suppression in phantoms and lower-extremity computed tomographic (CT) angiographic data sets. MATERIALS AND METHODS Using a three-material basis decomposition method for 80- and 140-kVp data, the accuracy of correctly identified contrast medium and calcium voxels and the mean attenuation before and after calcium suppression were computed. Experiments were first performed on a phantom of homogenous contrast medium and hydroxyapatite samples with mean attenuation of 57.2, 126, and 274 Hounsfield units (HU) and 50.0, 122, and 265 HU, respectively. Experiments were repeated in corresponding attenuation groups of voxels from manually segmented bones and contrast medium-enhanced arteries in a lower-extremity CT angiographic data set with mean attenuation of 293 and 434 HU, respectively. Calcium suppression in atherosclerotic plaques of a cadaveric specimen was also studied, using micro-computed tomography as a reference, and in a lower-extremity CT angiographic data set with substantial below-knee calcified plaques. RESULTS Higher concentrations showed increased accuracy of iodine and hydroxyapatite identification of 87.4%, 99.7%, and 99.9% and 88.0%, 95.0%, and 99.9%, respectively. Calcium suppression was also more accurate with higher concentrations of iodine and hydroxyapatite, with mean attenuation after suppression of 47.1, 122, and 263 HU and 7.14, 11.6, and 12.6 HU, respectively. Similar patterns were seen in the corresponding attenuation groups of the contrast medium-enhanced arteries and bone in the clinical data set, which had overall accuracy of 81.3% and 78.9%, respectively, and mean attenuation after calcium suppression of 254 and 73.7 HU, respectively. The suppression of calcified atherosclerotic plaque was accurate compared with the micro-CT reference; however, the suppression in the clinical data set showed probable inappropriate suppression of the small vessels. CONCLUSION Dual-energy computed tomography can detect and differentiate between contrast medium and calcified tissues, but its accuracy is dependent on the CT density of tissues and limited when CT attenuation is low.
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Differences in arterial compliance, microvascular function and venous capacitance between patients with heart failure and either preserved or reduced left ventricular systolic function.
Balmain, S, Padmanabhan, N, Ferrell, WR, Morton, JJ, McMurray, JJ
European journal of heart failure. 2007;(9):865-71
Abstract
BACKGROUND Up to 50% of patients with the clinical syndrome of heart failure have preserved left ventricular systolic function (HF-PSF). These patients may have abnormalities of ventriculo-vascular coupling, due to increased vascular and ventricular stiffness. METHODS We compared arterial compliance, microvascular vasodilator function and venous capacitance (VC) in 3 groups of patients (n=12 each) matched for the presence of coronary heart disease: 1) HF and preserved systolic function (HF-PSF), 2) HF and reduced systolic function (HF-RSF) and 3) controls (no HF, PSF). Arterial compliance was assessed by measuring aortic pulse wave velocity (PWV) with applanation tonometry. Cutaneous microvascular function was assessed using Laser Doppler imaging (LDI) coupled with iontophoresis of endothelium-dependent (acetylcholine) and -independent (sodium nitroprusside) vasodilators. VC was measured using venous occlusion plethysmography. RESULTS PWV was significantly higher in HF-PSF subjects than in both HF-RSF and control groups (10.7 [1.1], 8.9 [1.7] and 8.6 [2.1] m/s respectively, p<0.05). Acetylcholine and nitroprusside induced vasodilatation were equally impaired in HF-PSF and HF-RSF, as compared to controls (p<0.01). VC was higher in HF-RSF subjects compared with HF-PSF subjects (1.75 [0.41], 1.34 [0.34] ml/100 ml forearm vol. respectively, p<0.05). CONCLUSIONS These findings are consistent with a more marked increase in vascular stiffness in HF-PSF than in HF-RSF and suggest that arterial stiffness, dynamic vasodilator function and venous abnormalities may be implicated in the complex pathophysiology of HF-PSF.
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[Changes of elastic properties of magistral arteries in patients with ischemic heart disease during treatment with atorvastatin and simvastatin].
Iliukhin, OV, Kalganova, EL, Babkin, AA, Lopatin, IuM
Kardiologiia. 2005;(12):31-4
Abstract
AIM: To elucidate effect of atorvastatin and simvastatin on elastic properties and reactivity of large arteries in patients with ischemic heart disease. MATERIAL Patients (n=38) with ischemic heart disease receiving atorvastatin (10 mg/day, n=20) and simvastatin (20 mg/day, n=18). METHODS Elasticity of arteries was assessed by pulse wave propagation velocity measured by Coloson computer system. Test with reactive hyperemia was used for assessment of large muscular type vessels reactivity in response to blood flow augmentation was assessed by. RESULTS Treatment with statins for 6 months was associated with positive changes of elasticity of arteries of elastic type (-10.05% and -4.66% in atorvastatin and simvastatin treated patients, respectively) and endothelium dependent reactivity of arteries of muscular type (-16.01%, p<0.001 and -11.1% p<0.001 compared with initial values in atorvastatin and simvastatin treated patients, respectively). CONCLUSION Therapy with statins positively affects parameters of elasticity and reactivity of large arteries.
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Comparison of auto-moving table contrast-enhanced 3-D MRA and iodinated contrast-enhanced DSA for evaluating the lower-extremity arteries.
Ho, CF, Wu, MH, Wu, HM, Chang, CY, Chen, MC, Chou, TY
Journal of the Chinese Medical Association : JCMA. 2004;(10):511-20
Abstract
BACKGROUND This study was conducted to compare diagnostic efficacy of contrast-enhanced 3-dimensional magnetic resonance angiography (3-D MRA) with that of the conventional x-ray iodinated digital subtraction angiography (DSA) in patients with peripheral arterial occlusive diseases (PAOD). METHODS Twenty patients with a clinical diagnosis of PAOD participated in this study. All patients were evaluated with both contrast-enhanced 3-D MRA and conventional x-ray iodinated DSA for the arteries of their lower extremities. The DSA was performed by a selective catheterization into the bilateral common or superficial femoral arteries, whereas 3-D MRA was performed with an auto-moving table covering the vascular tree from aorta to the arteries of ankle regions with 1 bolus injection of a triple-dose (0.3 mmol/kg) contrast medium. The arteries were divided into 23 anatomic segments and graded by their appearance on a 1-4 scale (1 = normal, 4 = total occlusion or no visible vessel). Evaluators also compared the images of 3-D MRA with those of the conventional x-ray iodinated DSA (as gold standard) with respect to image quality. RESULTS There was a high agreement (k = 0.6-1.0) between 2 observers' interpretations of the images obtained from 3-D MRA and conventional DSA. The agreement within each observer was moderate to fair (k = 0.32-0.57), and the better agreement was found with the images above knee level than those below knee level. As for the image quality of 3-D MRA, the frequencies of showing a similar image quality were 57.5%, 55%, and 37.5% at the aortofemoral, femoropopliteal, and distal leg levels, respectively. CONCLUSIONS The main problem of the 3-D contrast enhanced MRA was the returned venous contamination of the image. It was particularly problematic for the areas below knee level. MRA can provide an initial evaluation for patients with PAOD, but cannot substitute for the conventional DSA as a precise diagnostic image modality for peripheral vascular diseases, especially for the distal legs.
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Physiologically based pharmacokinetic modeling of arterial - antecubital vein concentration difference.
Levitt, DG
BMC clinical pharmacology. 2004;:2
Abstract
BACKGROUND Modeling of pharmacokinetic parameters and pharmacodynamic actions requires knowledge of the arterial blood concentration. In most cases, experimental measurements are only available for a peripheral vein (usually antecubital) whose concentration may differ significantly from both arterial and central vein concentration. METHODS A physiologically based pharmacokinetic (PBPK) model for the tissues drained by the antecubital vein (referred to as "arm") is developed. It is assumed that the "arm" is composed of tissues with identical properties (partition coefficient, blood flow/gm) as the whole body tissues plus a new "tissue" representing skin arteriovenous shunts. The antecubital vein concentration depends on the following parameters: the fraction of "arm" blood flow contributed by muscle, skin, adipose, connective tissue and arteriovenous shunts, and the flow per gram of the arteriovenous shunt. The value of these parameters was investigated using simultaneous experimental measurements of arterial and antecubital concentrations for eight solutes: ethanol, thiopental, 99Tcm-diethylene triamine pentaacetate (DTPA), ketamine, D2O, acetone, methylene chloride and toluene. A new procedure is described that can be used to determine the arterial concentration for an arbitrary solute by deconvolution of the antecubital concentration. These procedures are implemented in PKQuest, a general PBPK program that is freely distributed http://www.pkquest.com. RESULTS One set of "standard arm" parameters provides an adequate description of the arterial/antecubital vein concentration for ethanol, DTPA, thiopental and ketamine. A significantly different set of "arm" parameters was required to describe the data for D2O, acetone, methylene chloride and toluene - probably because the "arm" is in a different physiological state. CONCLUSIONS Using the set of "standard arm" parameters, the antecubital vein concentration can be used to determine the whole body PBPK model parameters for an arbitrary solute without any additional adjustable parameters. Also, the antecubital vein concentration can be used to estimate the arterial concentration for an arbitrary input for solutes for which no arterial concentration data is available.