Li L.-P.,University of Chicago |
Li L.-P.,Center for Advanced Imaging |
Thacker J.,Northwestern University |
Franklin T.,Center for Advanced Imaging |
And 5 more authors.
Investigative Radiology | Year: 2014
Objective: The objective of this study was to evaluate the effects of potential renoprotective interventions such as the administration of N-acetylcysteine (NAC; antioxidant) and furosemide (diuretic) on intrarenal oxygenation as evaluated by blood oxygen level-dependent (BOLD) magnetic resonance imaging (MRI) in combination with urinary neutrophil gelatinase-associated lipocalin (NGAL) measurements. Materials and Methods: Rats received nitric oxide synthase inhibitor L-NAME (10 mg/kg) and cyclooxygenase inhibitor indomethacin (10 mg/kg) to induce the risk for developing iodinated contrast-induced acute kidney injury before receiving one of the interventions: NAC, furosemide, or placebo. One of the 3 iodinated contrast agents (iohexol, ioxaglate, or iodixanol) was then administered (1600-mg organic iodine per kilogram body weight). Fiftyfour Sprague-Dawley rats were allocated in a random order into 9 groups on the basis of the intervention and the contrast agent received. Blood-oxygen-level-dependent MRI-weighted images were acquired on a Siemens 3.0-T scanner using a multiple gradient recalled echo sequence at baseline, after L-NAME, indomethacin, interventions or placebo, and iodinated contrast agents. Data acquisition and analysis were performed in a blind fashion. R2∗ (=1/T2∗) maps were generated inline on the scanner. A mixed-effects growth curve model with first-order autoregressive variance-covariance was used to analyze the temporal data. Urinary NGAL, a marker of acute kidney injury, was measured at baseline, 2 and 4 hours after the contrast injection. Results: Compared with the placebo-treated rats, those treated with furosemide showed a significantly lower rate of increase in R2∗ (P < 0.05) in the renal inner stripe of the outer medulla. The rats treated with NAC showed a lower rate of increase in R2∗ compared with the controls, but the difference did not reach statistical significance. Urinary NGAL showed little to no increase in R2∗ after administration of iodixanol in the rats pretreated with furosemide but demonstrated significant increase in the rats pretreated with NAC or placebo (P < 0.05). Conclusions: This is the first study to evaluate the effects of interventions to mitigate the deleterious effects of contrast media using BOLD MRI. The rate of increase in R2∗ after administration of iodinated contrast is associated with acute renal injury as evaluated by NGAL. Further studies are warranted to determine the optimum dose of furosemide and NAC for mitigating the ill effects of contrast media. Because NGAL has been shown to be useful in humans to document iodinated contrast-induced acute kidney injury, the method presented in this study using BOLD MRI and NGAL measurements can be translated to humans. Copyright © 2014 Lippincott Williams & Wilkins.
Ortiz O.,Winthrop University |
Mathis J.M.,Center for Advanced Imaging
Neuroimaging Clinics of North America | Year: 2010
Vertebral augmentation techniques use image guidance for the percutaneous placement of spinal implants that stabilize a painful osteoporotic or pathologic vertebral compression fracture. The initial implant, acrylic bone cement, was injected through a bone needle into the vertebral body, a procedure referred to as vertebroplasty. A modification of this procedure, kyphoplasty, entails the temporary use of an inflatable balloon tamp before cement injection. Other techniques and the equipment required to perform these vertebral augmentation procedures have evolved significantly during the past two decades. It is now possible to perform vertebral body reconstruction in patients with painful fractures of compromised vertebrae with excellent outcomes in terms of sustainable pain relief and marked reduction in patient morbidity. © 2010 Elsevier Inc.
Undheim E.A.B.,Institute for Molecular Bioscience |
Undheim E.A.B.,Center for Advanced Imaging |
Hamilton B.R.,Materials Health Services |
Hamilton B.R.,University of Queensland |
And 5 more authors.
Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
Venom represents one of the most extreme manifestations of a chemical arms race. Venoms are complex biochemical arsenals, often containing hundreds to thousands of unique protein toxins. Despite their utility for prey capture, venoms are energetically expensive commodities, and consequently it is hypothesized that venom complexity is inversely related to the capacity of a venomous animal to physically subdue prey. Centipedes, one of the oldest yet least-studied venomous lineages, appear to defy this rule. Although scutigeromorph centipedes produce less complex venom than those secreted by scolopendrid centipedes, they appear to rely heavily on venom for prey capture. We show that the venom glands are large and well developed in both scutigerid and scolopendrid species, but that scutigerid forcipules lack the adaptations that allow scolopendrids to inflict physical damage on prey and predators. Moreover, we reveal that scolopendrid venom glands have evolved to accommodate a much larger number of secretory cells and, by using imaging mass spectrometry, we demonstrate that toxin production is heterogeneous across these secretory units. We propose that the differences in venom complexity between centipede orders are largely a result of morphological restrictions of the venom gland, and consequently there is a strong correlation between the morphological and biochemical complexity of this unique venom system. The current data add to the growing body of evidence that toxins are not expressed in a spatially homogenous manner within venom glands, and they suggest that the link between ecology and toxin evolution is more complex than previously thought. venom evolution , venom-gland morphology , centipede,mass spectrometry imaging ,venom optimization hypothesis.
PubMed | Center for Advanced Imaging, University of South Australia, Institute for Molecular Bioscience and Materials Health Services
Type: Journal Article | Journal: Proceedings of the National Academy of Sciences of the United States of America | Year: 2015
Venom represents one of the most extreme manifestations of a chemical arms race. Venoms are complex biochemical arsenals, often containing hundreds to thousands of unique protein toxins. Despite their utility for prey capture, venoms are energetically expensive commodities, and consequently it is hypothesized that venom complexity is inversely related to the capacity of a venomous animal to physically subdue prey. Centipedes, one of the oldest yet least-studied venomous lineages, appear to defy this rule. Although scutigeromorph centipedes produce less complex venom than those secreted by scolopendrid centipedes, they appear to rely heavily on venom for prey capture. We show that the venom glands are large and well developed in both scutigerid and scolopendrid species, but that scutigerid forcipules lack the adaptations that allow scolopendrids to inflict physical damage on prey and predators. Moreover, we reveal that scolopendrid venom glands have evolved to accommodate a much larger number of secretory cells and, by using imaging mass spectrometry, we demonstrate that toxin production is heterogeneous across these secretory units. We propose that the differences in venom complexity between centipede orders are largely a result of morphological restrictions of the venom gland, and consequently there is a strong correlation between the morphological and biochemical complexity of this unique venom system. The current data add to the growing body of evidence that toxins are not expressed in a spatially homogenous manner within venom glands, and they suggest that the link between ecology and toxin evolution is more complex than previously thought.
Bae H.,Spine Institute |
Bae H.,Spine Center |
Hatten H.P.,Indian River Radiology |
Linovitz R.,Core Orthopedic Medical Center |
And 8 more authors.
Spine | Year: 2012
STUDY DESIGN.: Randomized, controlled, prospective (AAOS therapeutic level I) trial conducted under Food and Drug Administration Investigational Device Exemption hypothesized noninferiority of a novel bioactive composite material to polymethylmethacrylate (PMMA). OBJECTIVE.: To determine the safety and efficacy of a new, nonresorbable bioactive composite (Cortoss) compared with PMMA, the standard treatment of vertebral compression fractures (VCFs). SUMMARY OF BACKGROUND DATA.: Vertebroplasty with PMMA, the widely adopted treatment for VCFs nonresponsive to conservative care, provides effective, immediate pain relief, but the material has received criticism for its properties. A new bioactive composite material designed specifically for vertebroplasty showed promising results in animals and nonrandomized clinical studies and was subsequently compared with PMMA in a randomized study. This study represents the first prospective study evaluating vertebroplasty comparing PMMA with another material with 24-month follow-up. METHODS.: Using 2:1 randomization, vertebroplasty was performed with Cortoss on 162 patients and PMMA on 94 patients. Inclusion criteria were painful osteoporotic VCFs with a visual analogue scale pain score of at least 50 mm on a 100-mm scale and at least 30% disability as measured by the Oswestry Disability Index. Evaluations at pretreatment, treatment day, and 7 posttreatment intervals out to 24 months included pain, disability, neurological status, adverse events, quality of life, patient satisfaction, analgesic use, and independently reviewed radiographs. RESULTS.: Noninferiority of Cortoss relative to PMMA was observed, with Cortoss-treated patients experiencing significant pain relief at 3 months (P = 0.0395) and better maintenance or improvement in function at 24 months (P = 0.0299). Incidence of serious device-related adverse events was 4.3% in both groups; none were life threatening. CONCLUSION.: Vertebroplasty using either Cortoss or PMMA provides effective, immediate, and lasting pain relief and prevents further loss of function. Both materials performed comparably at most time points; Cortoss demonstrated better results for pain reduction at 3 months and for function at 24 months. © 2012, Lippincott Williams & Wilkins.
Liu J.,University of Queensland |
Yan J.,University of Queensland |
Greer J.M.,University of Queensland |
Read S.J.,Royal Brisbane and Womens Hospital |
And 5 more authors.
International Journal of Neuroscience | Year: 2014
Human adrenomedullin (ADM), a 52-amino acid peptide, belongs to the calcitonin/calcitonin gene-related peptide (CGRP)/amylin peptide family. ADM acts as a multifunctional regulatory peptide and is upregulated in response to hypoxia. Previous microarray studies have found increased ADM gene (ADM) expression in peripheral blood cells of patients with stroke, however, it is unknown if an increased ADM level is correlated with severity of human ischemic stroke. This study investigated ADM expression in peripheral blood leukocytes (PBL) of healthy controls and subjects at day 1, week 1 and week 3 postacute ischemic stroke using rtPCR methodology. We found that ADM expression was significantly upregulated on the first day of stroke compared to the healthy subjects and the disease controls; the levels remained elevated for up to week 3. Further, ADM expression at day 1 was correlated with stroke severity measured by the National Institute of Healthy Stroke Scale (NIHSS), the modified Barthel Index (mBI) and the modified Rankin Scale (mRS). This could indicate that ADM expression level is related to the severity of tissue damage. We suggest that increased ADM expression in PBL after acute ischemic stroke is most likely to indicate that these cells have been subjected to hypoxia and that the magnitude of expression is likely to be related to the volume of hypoxic tissue. Hypoxia can affect lymphocytes function and could affect the immune response to stroke. The correlation of ADM expression level with the measures of stroke severity implicates ADM -a potential blood bio-marker in studies of ischemic stroke. Copyright © 2014 Informa Healthcare USA, Inc.
Li L.-P.,Center for Advanced Imaging |
Li L.-P.,University of Chicago |
Lu J.,University of Chicago |
Lu J.,NorthShore University HealthSystem |
And 5 more authors.
Investigative Radiology | Year: 2015
Objectives: The objective of this study was to assess whether streptozotocin (STZ)-induced diabetic rats develop iodinated contrast-induced acute kidney injury. The intrarenal R2∗ (=1/T2∗) was evaluated continuously before, during, and after contrast administration. Renal injury was confirmed using urinary neutrophil gelatinase-associated lipocalin measurements. Materials and Methods: Six Sprague-Dawley rats were administered with STZ to induce diabetes (group 1). R2∗ was measured before, during, and after administration of iodixanol. R2∗ readings were sampled from 4 renal regions: inner medulla, inner stripe of outer medulla (ISOM), outer stripe of outer medulla, and cortex. Peak R2∗ and initial upslope of R2∗ increase after iodinated contrast were calculated. Data from 12 nondiabetic rats pretreated with nitric oxide synthase and prostaglandin inhibitors to induce susceptibility to contrast-induced acute kidney injury (pretreatment model) from a previous study were reanalyzed for peak R2∗ and initial upslope of R2∗ increase after contrast. Six of these animals received saline (group 2), and the other 6 received furosemide (group 3) before iodixanol. Results: Peak R2∗ and initial upslope of R2∗ increase were used as bloodoxygenation- level-dependent response parameters. R2∗ in ISOM was comparable in all 3 groups before administration of furosemide/saline. Except for the furosemide group, ISOMshowed a rapid increase in R2∗ immediately after contrast administration. Unlike the L-NAME- and indomethacin-treated groups, the diabetic group showed a quick reversal of R2∗ toward baseline measurements after contrast administration. Urinary neutrophil gelatinase-associated lipocalin indicated significant increase in diabetic rats 4 hours after contrast administration. The observed trends with peak R2∗ and initial upslope of R2∗ increase in renal ISOM were in agreement with those of urinary neutrophil gelatinase-associated lipocalin. Conclusions: The STZ-induced diabetic rat may be suitable for studying the effects of iodinated contrast on renal oxygenation status and may mimic human condition closer than the pretreatment model described before. The peak R2∗ value and initial upslope of R2∗ in ISOM appear to be effective magnetic resonance imaging markers to predict renal injury after administration of an iodinated contrast agent. Copyright © 2015 Wolters Kluwer Health, Inc. All rights reserved.
Bennett T.M.,University of Queensland |
Bennett T.M.,Center for Advanced Imaging |
Jack K.S.,University of Queensland |
Thurecht K.J.,University of Queensland |
And 4 more authors.
Macromolecules | Year: 2016
Understanding the phase behavior of block copolymer/ionic liquid mixtures is an important step toward their implementation in commercial devices. Here we report a high throughput and systematic small-angle X-ray scattering study of the lyotropic phase behavior of a series of polystyrene-b-poly(methyl methacrylate) (PS-b-PMMA) block copolymers in the ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethane sulfonyl)imide (EMIM Tf2N). The ionic liquid induces disorder-order transitions for a number of low molecular weight systems, and the onset points of these transitions are used to calculate the dependence of the effective Flory-Huggins interaction parameter (χeff) on the ionic liquid concentration. This enabled construction of an experimental phase diagram, which reveals that after taking volumetric swelling into account, at higher ionic liquid concentrations, the experimental phase boundaries shift significantly when compared to theoretical calculations for block copolymer melts. It is also demonstrated that the scaling of the domain spacing with ionic liquid concentration is dependent on the molecular weight for low degrees of polymerization. Finally, it is demonstrated that the addition of the ionic liquid is able to induce phase separation in normally disordered block copolymers to achieve individual lamellar domains as narrow as 7.2 nm, which is significantly narrower than those for neat PS-b-PMMA. These findings should be an important tool in future investigations that target specific self-assembled morphologies to suit a desired application. © 2015 American Chemical Society.
PubMed | Center for Advanced Imaging, Mayo Medical School and Ben - Gurion University of the Negev
Type: Clinical Study | Journal: Journal of electrocardiology | Year: 2014
To determine if ECG repolarization measures can be used to detect small changes in serum potassium levels in hemodialysis patients.Signal-averaged ECGs were obtained from standard ECG leads in 12 patients before, during, and after dialysis. Based on physiological considerations, five repolarization-related ECG measures were chosen and automatically extracted for analysis: the slope of the T wave downstroke (T right slope), the amplitude of the T wave (T amplitude), the center of gravity (COG) of the T wave (T COG), the ratio of the amplitude of the T wave to amplitude of the R wave (T/R amplitude), and the center of gravity of the last 25% of the area under the T wave curve (T4 COG) (Fig.1).The correlations with potassium were statistically significant for T right slope (P<0.0001), T COG (P=0.007), T amplitude (P=0.0006) and T/R amplitude (P=0.03), but not T4 COG (P=0.13). Potassium changes as small as 0.2mmol/L were detectable.Small changes in blood potassium concentrations, within the normal range, resulted in quantifiable changes in the processed, signal-averaged ECG. This indicates that non-invasive, ECG-based potassium measurement is feasible and suggests that continuous or remote monitoring systems could be developed to detect early potassium deviations among high-risk patients, such as those with cardiovascular and renal diseases. The results of this feasibility study will need to be further confirmed in a larger cohort of patients.
PubMed | Mahatma Jyotiba Phule Rohilkhand University, Center for Advanced Imaging, Mayo Medical School and Ben - Gurion University of the Negev
Type: Journal Article | Journal: Journal of the American Heart Association | Year: 2016
Hyper- and hypokalemia are clinically silent, common in patients with renal or cardiac disease, and are life threatening. A noninvasive, unobtrusive, blood-free method for tracking potassium would be an important clinical advance.Two groups of hemodialysis patients (development group, n=26; validation group, n=19) underwent high-resolution digital ECG recordings and had 2 to 3 blood tests during dialysis. Using advanced signal processing, we developed a personalized regression model for each patient to noninvasively calculate potassium values during the second and third dialysis sessions using only the processed single-channel ECG. In addition, by analyzing the entire development groups first-visit data, we created a global model for all patients that was validated against subsequent sessions in the development group and in a separate validation group. This global model sought to predict potassium, based on the T wave characteristics, with no blood tests required. For the personalized model, we successfully calculated potassium values with an absolute error of 0.360.34 mmol/L (or 10% of the measured blood potassium). For the global model, potassium prediction was also accurate, with an absolute error of 0.440.47 mmol/L for the training group (or 11% of the measured blood potassium) and 0.50.42 for the validation set (or 12% of the measured blood potassium).The signal-processed ECG derived from a single lead can be used to calculate potassium values with clinically meaningful resolution using a strategy that requires no blood tests. This enables a cost-effective, noninvasive, unobtrusive strategy for potassium assessment that can be used during remote monitoring.