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Sample records for oral contrast agent

  1. Pineapple juice as a negative oral contrast agent in magnetic resonance cholangiopancreatography: a preliminary evaluation.

    PubMed

    Riordan, R D; Khonsari, M; Jeffries, J; Maskell, G F; Cook, P G

    2004-12-01

    The quality of magnetic resonance cholangiopancreatography (MRCP) images is frequently degraded by high signal from the gastrointestinal tract. The aim of this study is to evaluate pineapple juice (PJ) as an oral negative contrast agent in MRCP. Preliminary in vitro evaluation demonstrated that PJ shortened T(2) relaxation time and hence decreased T(2) signal intensity on a standard MRCP sequence to a similar degree to a commercially available negative contrast agent (ferumoxsil). Electrothermal atomic absorption spectrometry assay demonstrated a high manganese concentration in PJ of 2.76 mg dl(-1), which is likely to be responsible for its T(2) imaging properties. MRCP was subsequently performed in 10 healthy volunteers, before and at 15 min and 30 min following ingestion of 400 ml of PJ. Images were assessed blindly by two Consultant Radiologists using a standard grading technique based on contrast effect (degree of suppression of bowel signal), and image effect (diagnostic quality). There were statistically significant improvements in contrast and image effect between pre and post PJ images. There was particularly significant improvement in visualization of the pancreatic duct, but no significant difference between 15 min and 30 min post PJ images. Visualization of the ampulla, common bile duct, common hepatic and central intrahepatic ducts were also significantly improved at 15 min following PJ. Our results demonstrate that PJ, may be used as an alternative to commercially available negative oral contrast agent in MRCP. PMID:15569640

  2. Oral manganese as an MRI contrast agent for the detection of nociceptive activity.

    PubMed

    Jacobs, Kathleen E; Behera, Deepak; Rosenberg, Jarrett; Gold, Garry; Moseley, Michael; Yeomans, David; Biswal, Sandip

    2012-04-01

    The ability of divalent manganese to enter neurons via calcium channels makes manganese an excellent MRI contrast agent for the imaging of nociception, the afferent neuronal encoding of pain perception. There is growing evidence that nociceptive neurons possess increased expression and activity of calcium channels, which would allow for the selective accumulation of manganese at these sites. In this study, we show that oral manganese chloride leads to increased enhancement of peripheral nerves involved in nociception on T(1)-weighted MRI. Oral rather than intravenous administration was chosen for its potentially better safety profile, making it a better candidate for clinical translation with important applications, such as pain diagnosis, therapy and research. The spared nerve injury (SNI) model of neuropathic pain was used for the purposes of this study. SNI rats were given, sequentially, increasing amounts of manganese chloride (lowest, 2.29 mg/100 g weight; highest, 20.6 mg/100 g weight) with alanine and vitamin D(3) by oral gavage. Compared with controls, SNI rats demonstrated increased signal-to-background ratios on T(1)-weighted fast spin echo MRI, which was confirmed by and correlated strongly with spectrometry measurements of nerve manganese concentration. We also found the difference between SNI and control rats to be greater at 48 h than at 24 h after dosing, indicating increased manganese retention in addition to increased manganese uptake in nociceptive nerves. This study demonstrates that oral manganese is a viable method for the imaging of nerves associated with increased nociceptive activity. PMID:22447731

  3. Comparative Study of Pineapple Juice as a Negative Oral Contrast Agent in Magnetic Resonance Cholangiopancreatography

    PubMed Central

    2015-01-01

    Objectives: The aim of this study was to compare the image quality of magnetic resonance Cholangiopancreatography (MRCP) using Pineapple Juice (PJ) or ranitidine as negative oral contrast agents and no agent. Materials and Methods: MRCP images of patients administered PJ (n = 117) or Ranitidine (n = 110) at random, and patients without an agent (n = 50) were evaluated. The subjective image quality of the overall, extra hepatic bile duct and pancreatic duct and the degree of elimination of gastrointestinal fluid were scored by two blinded radiologists. Results were compared using Mann-Whitney’s U-test. Results: The degrees of elimination of gastro duodenal fluid of PJ and ranitidine were significantly better than those without an agent (p < 0.01 and p < 0.01, respectively). The subjective image quality of PJ of the overall and extra hepatic bile duct were significantly better, although no significant differences for ranitidine were observed compared with those without an agent (p < 0.01 and p =0.23, p = 0.025 and p = 0.18). There were no significant differences for the pancreatic duct (p = 0.13 and p = 0.20), nor were there any significant differences in the evaluations between PJ and ranitidine (p = 0.21 and p = 0.96). Conclusion: PJ showed better performance compared to that of conventional ranitidine in terms of pancreatic and biliary depiction and safety. PMID:25738055

  4. Confocal Microscopy and Molecular-Specific Optical Contrast Agents for the Detection of Oral Neoplasia

    PubMed Central

    Carlson, Alicia L.; Gillenwater, Ann M.; Williams, Michelle D.; El-Naggar, Adel K.; Richards-Kortum, R. R.

    2009-01-01

    Using current clinical diagnostic techniques, it is difficult to visualize tumor morphology and architecture at the cellular level, which is necessary for diagnostic localization of pathologic lesions. Optical imaging techniques have the potential to address this clinical need by providing real-time, sub-cellular resolution images. This paper describes the use of dual mode confocal microscopy and optical molecular-specific contrast agents to image tissue architecture, cellular morphology, and sub-cellular molecular features of normal and neoplastic oral tissues. Fresh tissue slices were prepared from 33 biopsies of clinically normal and abnormal oral mucosa obtained from 14 patients. Reflectance confocal images were acquired after the application of 6% acetic acid, and fluorescence confocal images were acquired after the application of a fluorescence contrast agent targeting the epidermal growth factor receptor (EGFR). The dual imaging modes provided images similar to light microscopy of hematoxylin and eosin and immunohistochemistry staining, but from thick fresh tissue slices. Reflectance images provided information on the architecture of the tissue and the cellular morphology. The nuclear-to-cytoplasmic (N/C) ratio from the reflectance images was at least 7.5 times greater for the carcinoma than the corresponding normal samples, except for one case of highly keratinized carcinoma. Separation of carcinoma from normal and mild dysplasia was achieved using this ratio (p<0.01). Fluorescence images of EGFR expression yielded a mean fluorescence labeling intensity (FLI) that was at least 2.7 times higher for severe dysplasia and carcinoma samples than for the corresponding normal sample, and could be used to distinguish carcinoma from normal and mild dysplasia (p<0.01). Analyzed together, the N/C ratio and the mean FLI may improve the ability to distinguish carcinoma from normal squamous epithelium. PMID:17877424

  5. A clinical trial of oral cholecystography using combinations of contrast agents and two consecutive doses.

    PubMed

    Thoeni, R F; Moss, A A

    1982-07-01

    Fifteen healthy volunteers underwent a randomized trial of oral cholecystography (OCG) using 5 different combinations of contrast agents given as 2 consecutive doses: Telepaque (iopanoic acid) given with food (TF) or without food (T), Bilopaque (sodium tyropanoate) given without food, and a combination of both agents (TF-B). The density of gallbladder opacification was judged visually on a scale of 1+ to 4+ and quantitatively by a densitometric method. Comparison of gallbladder opacification on the first and second days of the study revealed 52 of 75 (70%) combinations (TF-T, TF-TF,T-T, TF-B, B-B) resulted in improved opacification, 17% in equal opacification, and 13% in worse opacification on day 2. The TF-B combination showed the highest number (9) of excellent (grade 4+) results and the lowest number (2) of poor (grade 1+ and 2+) results, gave the best opacification in 8 volunteers, and had the highest average density difference (0.32) between first- and second-day opacifications. The TF-TF combination was the next most effective, and the T-T combination was the least effective. The results indicate that OCG in 2 consecutive doses is superior to single-dose OCG, and that a combination of TF-B or TF-TF will provide the greatest gallbladder opacification. The TF-B combination is recommended because of better patient tolerance. PMID:7045975

  6. Small bowel obstruction following computed tomography and magnetic resonance enterography using psyllium seed husk as an oral contrast agent.

    PubMed

    Chen, Yingming Amy; Cervini, Patrick; Kirpalani, Anish; Vlachou, Paraskevi A; Grover, Samir C; Colak, Errol

    2014-01-01

    The authors report a case series describing four patients who developed small bowel obstruction following the use of psyllium seed husk as an oral contrast agent for computed tomography or magnetic resonance enterography. Radiologists who oversee computed tomography and magnetic resonance enterography should be aware of this potential complication when using psyllium seed husk and other bulking agents, particularly when imaging patients with known or suspected small bowel strictures or active inflammation. PMID:25157531

  7. Small bowel obstruction following computed tomography and magnetic resonance enterography using psyllium seed husk as an oral contrast agent

    PubMed Central

    Chen, Yingming Amy; Cervini, Patrick; Kirpalani, Anish; Vlachou, Paraskevi A; Grover, Samir C; Colak, Errol

    2014-01-01

    The authors report a case series describing four patients who developed small bowel obstruction following the use of psyllium seed husk as an oral contrast agent for computed tomography or magnetic resonance enterography. Radiologists who oversee computed tomography and magnetic resonance enterography should be aware of this potential complication when using psyllium seed husk and other bulking agents, particularly when imaging patients with known or suspected small bowel strictures or active inflammation. PMID:25157531

  8. Comparison of 3% sorbitol vs psyllium fibre as oral contrast agents in MR enterography

    PubMed Central

    Saini, S; Colak, E; Anthwal, S; Vlachou, P A; Raikhlin, A

    2014-01-01

    Objective: To compare the degree of small bowel distension achieved by 3% sorbitol, a high osmolarity solution, and a psyllium-based bulk fibre as oral contrast agents (OCAs) in MR enterography (MRE). Methods: This retrospective study was approved by our institutional review board. A total of 45 consecutive normal MRE examinations (sorbitol, n = 20; psyllium, n = 25) were reviewed. The patients received either 1.5 l of 3% sorbitol or 2 l of 1.6 g kg−1 psyllium prior to imaging. Quantitative small bowel distension measurements were taken in five segments: proximal jejunum, distal jejunum, proximal ileum, distal ileum and terminal ileum by two independent radiologists. Distension in these five segments was also qualitatively graded from 0 (very poor) to 4 (excellent) by two additional independent radiologists. Statistical analysis comparing the groups and assessing agreement included intraclass coefficients, Student's t-test and Mann–Whitney U-test. Results: Small bowel distension was not significantly different in any of the five small bowel segments between the use of sorbitol and psyllium as OCAs in both the qualitative (p = 0.338–0.908) and quantitative assessments (p = 0.083–0.856). The mean bowel distension achieved was 20.1 ± 2.2 mm for sorbitol and 19.8 ± 2.5 mm for psyllium (p = 0.722). Visualization of the ileum was good or excellent in 65% of the examinations in both groups. Conclusion: Sorbitol and psyllium are not significantly different at distending the small bowel and both may be used as OCAs for MRE studies. Advances in knowledge: This is the first study to directly compare the degree of distension in MRE between these two common, readily available and inexpensive OCAs. PMID:25062448

  9. A potentially artifact-free oral contrast agent for gastrointestinal MRI.

    PubMed

    Liebig, T; Stoupis, C; Ros, P R; Ballinger, J R; Briggs, R W

    1993-11-01

    The combination of diamagnetic barium sulfate and superparamagnetic iron oxide (SPIO) in one suspension produces a macroscopic cancellation of positive and negative magnetic susceptibility components that can potentially eliminate susceptibility artifacts even with gradient echo pulse sequences. The relaxation properties that make the SPIO suspension a useful negative contrast agent are retained. PMID:8259066

  10. Study of suspending agents for gadolinium(III)-exchanged hectorite. An oral magnetic resonance imaging contrast agent

    SciTech Connect

    Balkus, K.J. Jr.; Shi, J.

    1996-12-25

    Clays modified with paramagnetic ions have been shown to be effective magnetic resonance imaging contrast agents. The efficacy in part relies on the suspension of the small clay particles in aqueous solution. In this study a series of macromolecules were eveluated as suspending agents for Gd(III) ion exchanged hectorite clay in water. The room temperature relaxivities for the Gd-hectorite clays were enhanced by the addition of poly(ethylene oxide), poly(ethylene glycol), cyclodextrins, and cholic acid to aqueous suspensions. Additionally, there was no evidence of free Gd(III) in solution in the presence of these suspending agents. In contrast the combination of alginic acid or poly(sodium 4-styrenesulfonate) with the clays resulted in release of the Gd(III) into solution. Xanthan gum, which is often used as an emulsifier and stabilizer in food products, forms a viscous suspension but also reacts with free Gd(III) ions. 25 refs., 10 figs., 2 tabs.

  11. Oral cancer screening approach based on labeling exfoliated oral cells with molecularly-targeted optical contrast agents

    NASA Astrophysics Data System (ADS)

    Leautaud, Veronica; Horres, Charles R.; Bhattar, Vijayashree S.; Williams, Michelle D.; Gillenwater, Ann M.; Richards-Kortum, Rebecca R.

    2011-03-01

    Early detection is a potential key to improving the survival rates of oral cancer patients and reducing the morbidity associated with treatment. We seek to improve upon methods of detecting of early malignancies with oral brush biopsies by using immunofluorescence-based assessment of the expression of multiple well-described markers commonly overexpressed in oral cancers, such as Epidermal Growth Factor Receptor (EGFR) and Cytokeratin 8 (CK8). Furthermore, since abnormal cells are often scarce in brush biopsy samples, we seek to use magnetic microparticles targeted to these markers as a means of enriching the concentration of abnormal cells. Finally, we plan to conduct a small pilot study using these methods with brush biopsies from patients of the M. D. Anderson Cancer Center Head and Neck Clinic.

  12. Gadofullerene MRI contrast agents.

    PubMed

    Bolskar, Robert D

    2008-04-01

    A promising new class of MRI contrast-enhancing agents with high relaxivities is based on gadolinium-containing metallofullerenes, which are also termed gadofullerenes. Detailed study of the water-proton relaxivity properties and intermolecular nanoclustering behavior of gadofullerene derivatives has revealed valuable information about their relaxivity mechanisms and given a deeper understanding of this new class of paramagnetic contrast agent. Here, the latest findings on water-solubilized gadofullerene materials and how these findings relate to their future applications in MRI are reviewed and discussed. PMID:18373426

  13. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, Paul H.; Brainard, James R.; Jarvinen, Gordon D.; Ryan, Robert R.

    1997-01-01

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC.sub.16 H.sub.14 N.sub.6. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques.

  14. Nuclear magnetic resonance contrast agents

    DOEpatents

    Smith, P.H.; Brainard, J.R.; Jarvinen, G.D.; Ryan, R.R.

    1997-12-30

    A family of contrast agents for use in magnetic resonance imaging and a method of enhancing the contrast of magnetic resonance images of an object by incorporating a contrast agent of this invention into the object prior to forming the images or during formation of the images. A contrast agent of this invention is a paramagnetic lanthanide hexaazamacrocyclic molecule, where a basic example has the formula LnC{sub 16}H{sub 14}N{sub 6}. Important applications of the invention are in medical diagnosis, treatment, and research, where images of portions of a human body are formed by means of magnetic resonance techniques. 10 figs.

  15. Environmentally responsive MRI contrast agents

    PubMed Central

    Davies, Gemma-Louise; Kramberger, Iris; Davis, Jason J.

    2015-01-01

    Biomedical imaging techniques can provide a vast amount of anatomical information, enabling diagnosis and the monitoring of disease and treatment profile. MRI uniquely offers convenient, non-invasive, high resolution tomographic imaging. A considerable amount of effort has been invested, across several decades, in the design of non toxic paramagnetic contrast agents capable of enhancing positive MRI signal contrast. Recently, focus has shifted towards the development of agents capable of specifically reporting on their local biochemical environment, where a switch in image contrast is triggered by a specific stimulus/biochemical variable. Such an ability would not only strengthen diagnosis but also provide unique disease-specific biochemical insight. This feature article focuses on recent progress in the development of MRI contrast switching with molecular, macromolecular and nanoparticle-based agents. PMID:24040650

  16. Clinical Comparison of Two Contrast Agents for Oral Cholecystography: Radiologic Efficacy and Drug Safety of Iopanoic Acid and Iopronic Acid 1

    PubMed Central

    Hedlund, Laurence; Putman, Charles E.; Burrell, Morton

    1979-01-01

    Oral doses of either iopronic acid (4.5 g Oravue, Squibb) or iopanoic acid (3 g Telepaque, Winthrop) were given to 98 patients requiring cholecystography. Radiographs were taken 13 to 16 hours after treatment showed good to excellent gallbladder opacification in 44 percent of patients after the first dose of iopronic acid and in an additional 29 percent after a second dose. Similar opacification occurred in 42 percent of patients after the first dose of iopanoic acid and in 34 percent after a second dose. Drug-related abnormalities in blood and urine tests occurred about equally in both groups and one patient in each group exhibited a clinically adverse reaction (diarrhea). Thus, the performance (radiographic efficacy and drug safety) of the new contrast agent, iopronic acid, was similar to a widely used drug, iopanoic acid. PMID:380184

  17. Polycatechol Nanoparticle MRI Contrast Agents.

    PubMed

    Li, Yiwen; Huang, Yuran; Wang, Zhao; Carniato, Fabio; Xie, Yijun; Patterson, Joseph P; Thompson, Matthew P; Andolina, Christopher M; Ditri, Treffly B; Millstone, Jill E; Figueroa, Joshua S; Rinehart, Jeffrey D; Scadeng, Miriam; Botta, Mauro; Gianneschi, Nathan C

    2016-02-01

    Amphiphilic triblock copolymers containing Fe(III) -catecholate complexes formulated as spherical- or cylindrical-shaped micellar nanoparticles (SMN and CMN, respectively) are described as new T1-weighted agents with high relaxivity, low cytotoxicity, and long-term stability in biological fluids. Relaxivities of both SMN and CMN exceed those of established gadolinium chelates across a wide range of magnetic field strengths. Interestingly, shape-dependent behavior is observed in terms of the particles' interactions with HeLa cells, with CMN exhibiting enhanced uptake and contrast via magnetic resonance imaging (MRI) compared with SMN. These results suggest that control over soft nanoparticle shape will provide an avenue for optimization of particle-based contrast agents as biodiagnostics. The polycatechol nanoparticles are proposed as suitable for preclinical investigations into their viability as gadolinium-free, safe, and effective imaging agents for MRI contrast enhancement. PMID:26681255

  18. A relaxometric method for the assessment of intestinal permeability based on the oral administration of gadolinium-based MRI contrast agents.

    PubMed

    Gianolio, Eliana; Boffa, Cinzia; Orecchia, Valeria; Bardini, Paola; Catanzaro, Valeria; Poli, Valeria; Aime, Silvio

    2016-04-01

    Herein, a new relaxometric method for the assessment of intestinal permeability based on the oral administration of clinically approved gadolinium (Gd)-based MRI contrast agents (CAs) is proposed. The fast, easily performed and cheap measurement of the longitudinal water proton relaxation rate (R1 ) in urine reports the amount of paramagnetic probe that has escaped the gastrointestinal tract. The proposed method appears to be a compelling alternative to the available methods for the assessment of intestinal permeability. The method was tested on the murine model of dextran sulfate sodium (DSS)-induced colitis in comparison with healthy mice. Three CAs were tested, namely ProHance®, MultiHance® and Magnevist®. Urine was collected for 24 h after the oral ingestion of the Gd-containing CA at day 3-4 (severe damage stage) and day 8-9 (recovery stage) after treatment with DSS. The Gd content in urine measured by (1) H relaxometry was confirmed by inductively coupled plasma-mass spectrometry (ICP-MS). The extent of urinary excretion was given as a percentage of excreted Gd over the total ingested dose. The method was validated by comparing the results obtained with the established methodology based on the lactulose/mannitol and sucralose tests. For ProHance and Magnevist, the excreted amounts in the severe stage of damage were 2.5-3 times higher than in control mice. At the recovery stage, no significant differences were observed with respect to healthy mice. Overall, a very good correlation with the lactulose/mannitol and sucralose results was obtained. In the case of MultiHance, the percentage of excreted Gd complex was not significantly different from that of control mice in either the severe or recovery stages. The difference from ProHance and Magnevist was explained on the basis of the (known) partial biliary excretion of MultiHance in mice. Copyright © 2016 John Wiley & Sons, Ltd. PMID:26866929

  19. Oral agents in multiple sclerosis.

    PubMed

    Lorefice, L; Fenu, G; Frau, J; Coghe, G C; Marrosu, M G; Cocco, E

    2015-01-01

    Multiple sclerosis (MS) is a complex autoimmune disease of the central nervous system. Disease-modifying drugs licensed for MS treatment have been developed to reduce relapse rates and halt disease progression. The majority of current MS drugs involve regular, parenteral administration, affecting long-term adherence and thus reducing treatment efficacy. Over the last two decades great progress has been made towards developing new MS therapies with different modes of action and biologic effects. In particular, oral drugs have generated much interest because of their convenience and positive impact on medication adherence. Fingolimod was the first launched oral treatment for relapsing-remitting MS; recently, Teriflunomide and Dimethyl fumarate have also been approved as oral disease-modifying agents. In this review, we summarize and discuss the history, pharmacodynamics, efficacy, and safety of oral agents that have been approved or are under development for the selective treatment of MS. PMID:25924620

  20. "Basic MR Relaxation Mechanisms & Contrast Agent Design"

    PubMed Central

    De León-Rodríguez, Luis M.; Martins, André F.; Pinho, Marco; Rofsky, Neil; Sherry, A. Dean

    2015-01-01

    The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we will detail the many important considerations when pursuing the design and use of MR contrast media. We will offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand based contrast agents. We will discuss the mechanisms involved in magnetic resonance relaxation in the context of probe design strategies. A brief description of currently available contrast agents will be accompanied by an in-depth discussion that highlights promising MRI contrast agents in development for future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. PMID:25975847

  1. Frequently asked questions: iodinated contrast agents.

    PubMed

    Bettmann, Michael A

    2004-10-01

    Although iodinated contrast agents are safe and widely used, adverse events occur and questions remain about their use, safety, and interactions. Some questions are easily answered and others still require extensive investigation. For one frequent question--is informed consent necessary before all contrast media injections--the simple answer is no. Another question concerns use of contrast media in patients with prior reactions or allergies. Contrast agents can be safely used in such patients, but special care must be taken to be aware of what the previous reaction was and to be ready to treat any reaction. The protective role of pre-treatment with steroids is well established for minor reactions, but they may not prevent major reactions. It is important to realize that even life-threatening, anaphylactoid reactions are not the result of a true allergy to contrast media. Many questions arise about contrast agent-induced nephropathy. Baseline serum creatinine values should be obtained in patients who are at risk, not all patients. The incidence and natural history of contrast agent-induced nephropathy remain unclear. It occurs only in patients with compromised renal function before contrast agent injection, but even patients with normal serum creatinine levels can have renal dysfunction. Calculated creatinine clearance is a better way to determine risk and to follow this complication. The outcome in almost all patients is benign, with progression to end-stage renal disease being rare. The major risk factors, in addition to renal dysfunction, are long-standing diabetes mellitus, dehydration, and use of other nephrotoxic medications. Recent work in preventing and ameliorating contrast agent-induced nephropathy with N-acetyl cysteine, substitution of an isosmolal nonionic contrast agent, and various hydration regimens has been promising. Another common concern is use of iodinated contrast agents in pregnant or breast-feeding women. In both cases, there is no evidence

  2. Contrast agent choice for intravenous coronary angiography

    SciTech Connect

    Zeman, H.D.; Siddons, D.P.

    1989-01-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation x-rays and an iodine containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic x-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the x-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation x-rays is visualizing a coronary artery through the left ventricle or aorta which also contains a contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth.

  3. Contrast agent choice for intravenous coronary angiography

    NASA Astrophysics Data System (ADS)

    Zeman, H. D.; Siddons, D. P.

    1990-05-01

    The screening of the general population for coronary artery disease would be practical if a method existed for visualizing the extent of occlusion after an intravenous injection of contrast agent. Measurements performed with monochromatic synchrotron radiation X-rays and an iodine-containing contrast agent at the Stanford Synchrotron Radiation Laboratory have shown that such an intravenous angiography procedure would be possible with an adequately intense monochromatic X-ray source. Because of the size and cost of synchrotron radiation facilities it would be desirable to make the most efficient use of the intensity available, while reducing as much as possible the radiation dose experienced by the patient. By choosing contrast agents containing elements with a higher atomic number than iodine, it is possible to both improve the image quality and reduce the patient radiation dose, while using the same synchrotron radiation source. By using Si monochromator crystals with a small mosaic spread, it is possible to increase the X-ray flux available for imaging by over an order of magnitude, without any changes in the storage ring or wiggler magnet. The most critical imaging task for intravenous coronary angiography utilizing synchrotron radiation X-rays is visualizing a coronary artery through the left ventricle or aorta which also contain contrast agent. Calculations have been made of the signal to noise ratio expected for this imaging task for various contrast agents with atomic numbers between that of iodine and bismuth. The X-ray energy spectrum of the X-17 superconduction wiggler beam line at the National Synchrotron Light Source at Brookhaven National Laboratory has been used for these calculations. Both perfect Si crystals and Si crystals with a small mosaic spread are considered as monochromators. Contrast agents containing Gd or Yb seem to have about the optimal calculated signal to noise ratio. Gd-DTPA is already approved for use as a contrast agent for

  4. Nanoparticles of gadolinium-incorporated Prussian blue with PEG coating as an effective oral MRI contrast agent for gastrointestinal tract imaging.

    PubMed

    Perera, Vindya S; Chen, Guojun; Cai, Qing; Huang, Songping D

    2016-03-01

    Biocompatible nanoparticles of gadolinium-incorporated Prussian blue with the empirical formula K0.94Gd0.02Fe[Fe(CN)6] exhibit extremely high stability against the release of Gd(3+) and CN(-) ions under the acidic conditions similar to stomach juice. The high r1 relaxivity, low cytotoxicity and the ability of such nanoparticles to penetrate the cell membrane suggest that this coordination-polymer structural platform offers a unique opportunity for developing the next generation of T1-weighted oral cellular MRI probes for the early detection of tumors in the gastrointestinal tract. PMID:26890149

  5. Multifunctional nanoparticles as coupled contrast agents

    PubMed Central

    Jin, Yongdong; Jia, Congxian; Huang, Sheng-Wen; O’Donnell, Matthew; Gao, Xiaohu

    2011-01-01

    Engineering compact imaging probes with highly integrated modalities is a key focus in bionanotechnology and will have profound impact on molecular diagnostics, imaging, and therapeutics. However, combining multiple components on a nanometer scale to create new imaging modalities unavailable from individual components has proven challenging. Here, we demonstrate iron oxide and gold coupled core-shell nanoparticles with well defined structural characteristics (e.g., size, shell thickness, and core-shell separation) and physical properties (e.g., electronic, magnetic, optical, thermal, and acoustic). The resulting multifunctional nanoprobes not only offer contrast for electron microscopy, magnetic resonance imaging, and scattering-based imaging, but more importantly, enable a new imaging mode, magnetomotive photoacoustic (mmPA) imaging, with remarkable contrast enhancement compared to PA images using conventional nanoparticle contrast agents. PMID:20975706

  6. Optical imaging with dynamic contrast agents.

    PubMed

    Wei, Qingshan; Wei, Alexander

    2011-01-24

    Biological imaging applications often employ molecular probes or nanoparticles for enhanced contrast. However, resolution and detection are still often limited by the intrinsic heterogeneity of the sample, which can produce high levels of background that obscure the signals of interest. Herein, we describe approaches to overcome this obstacle based on the concept of dynamic contrast: a strategy for elucidating signals by the suppression or removal of background noise. Dynamic contrast mechanisms can greatly reduce the loading requirement of contrast agents, and may be especially useful for single-probe imaging. Dynamic contrast modalities are also platform-independent, and can enhance the performance of sophisticated biomedical imaging systems or simple optical microscopes alike. Dynamic contrast is performed in two stages: 1) a signal modulation scheme to introduce time-dependent changes in amplitude or phase, and 2) a demodulation step for signal recovery. Optical signals can be coupled with magnetic nanoparticles, photoswitchable probes, or plasmon-resonant nanostructures for modulation by magnetomotive, photonic, or photothermal mechanisms, respectively. With respect to image demodulation, many of the strategies developed for signal processing in electronics and communication technologies can also be applied toward the editing of digital images. The image-processing step can be as simple as differential imaging, or may involve multiple reference points for deconvolution by using cross-correlation algorithms. Periodic signals are particularly amenable to image demodulation strategies based on Fourier transform; the contrast of the demodulated signal increases with acquisition time, and modulation frequencies in the kHz range are possible. Dynamic contrast is an emerging topic with considerable room for development, both with respect to molecular or nanoscale probes for signal modulation, and also to methods for more efficient image processing and editing. PMID

  7. Nanoparticle contrast agents for optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Gabriele, Michelle Lynn

    Optical coherence tomography (OCT) provides real-time, objective, in-vivo, optical cross-sectional representations of the retina and optic nerve. Recent innovations in image acquisition, including the incorporation of Fourier/spectral-domain detection, have improved imaging speed, sensitivity and resolution. Still, there remain specific structures within ocular OCT images, such as retinal ganglion cells (RGCs), which are of clinical interest but consistently have low contrast. This makes it difficult to differentiate between surrounding layers and structures. The objectives of this project were: (1) To establish a reliable method for OCT imaging of the healthy and diseased mouse eye in order to provide a platform for testing the utility of OCT contrast agents for ocular imaging, (2) To develop antibody-conjugated gold nanoparticles suitable for targeting specific structures and enhancing OCT image contrast in the mouse eye, and (3) To examine the localized contrast-enhancing ability and biocompatibility of gold nanoparticle contrast agents in-vivo. Our organizing hypotheses were that nanoparticles could improve contrast by modulating the intensity of backscattered light detected by OCT and that they could be directed to ocular structures of interest using antibodies specific to cellular markers. A reproducible method for imaging the mouse retina and quantifying retinal thickness was developed and this technique was then applied to a mouse model for retinal ganglion cell loss, optic nerve crush. Gold nanorods were designed specifically to augment the backscattering OCT signal at the same wavelengths of light used in current ophthalmic OCT imaging schemes (resonant wavelength lambda = 840 nm). Anti-CD90.1 (Thy1.1) antibodies were conjugated to the gold nanorods and a protocol for characterization of the success of antibody conjugation was developed. Upon injection, the gold nanorods were found to remain in the vitreous post-injection, with many consumed by an early

  8. Photoacoustic cell for ultrasound contrast agent characterization.

    PubMed

    Alippi, A; Bettucci, A; Biagioni, A; D'Orazio, A; Germano, M; Passeri, D

    2010-10-01

    Photoacoustics has emerged as a tool for the study of liquid gel suspension behavior and has been recently employed in a number of new biomedical applications. In this paper, a photoacoustic sensor is presented which was designed and realized for analyzing photothermal signals from solutions filled with microbubbles, commonly used as ultrasound contrast agents in echographic imaging techniques. It is a closed cell device, where photothermal volume variation of an aqueous solution produces the periodic deflection of a thin membrane closing the cell at the end of a short pipe. The cell then acts as a Helmholtz resonator, where the displacement of the membrane is measured through a laser probe interferometer, whereas photoacoustic signal is generated by a laser chopped light beam impinging onto the solution through a glass window. Particularly, the microbubble shell has been modeled through an effective surface tension parameter, which has been then evaluated from experimental data through the shift of the resonance frequencies of the photoacoustic sensor. This shift of the resonance frequencies of the photoacoustic sensor caused by microbubble solutions is high enough for making such a cell a reliable tool for testing ultrasound contrast agent, particularly for bubble shell characterization. PMID:21034110

  9. Photoacoustic cell for ultrasound contrast agent characterization

    NASA Astrophysics Data System (ADS)

    Alippi, A.; Bettucci, A.; Biagioni, A.; D'Orazio, A.; Germano, M.; Passeri, D.

    2010-10-01

    Photoacoustics has emerged as a tool for the study of liquid gel suspension behavior and has been recently employed in a number of new biomedical applications. In this paper, a photoacoustic sensor is presented which was designed and realized for analyzing photothermal signals from solutions filled with microbubbles, commonly used as ultrasound contrast agents in echographic imaging techniques. It is a closed cell device, where photothermal volume variation of an aqueous solution produces the periodic deflection of a thin membrane closing the cell at the end of a short pipe. The cell then acts as a Helmholtz resonator, where the displacement of the membrane is measured through a laser probe interferometer, whereas photoacoustic signal is generated by a laser chopped light beam impinging onto the solution through a glass window. Particularly, the microbubble shell has been modeled through an effective surface tension parameter, which has been then evaluated from experimental data through the shift of the resonance frequencies of the photoacoustic sensor. This shift of the resonance frequencies of the photoacoustic sensor caused by microbubble solutions is high enough for making such a cell a reliable tool for testing ultrasound contrast agent, particularly for bubble shell characterization.

  10. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    PubMed Central

    Sinharay, Sanhita; Pagel, Mark D.

    2016-01-01

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

  11. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection

    NASA Astrophysics Data System (ADS)

    Sinharay, Sanhita; Pagel, Mark D.

    2016-06-01

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized 13C to detect the agent with outstanding sensitivity. These hyperpolarized 13C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection.

  12. Advances in Magnetic Resonance Imaging Contrast Agents for Biomarker Detection.

    PubMed

    Sinharay, Sanhita; Pagel, Mark D

    2016-06-12

    Recent advances in magnetic resonance imaging (MRI) contrast agents have provided new capabilities for biomarker detection through molecular imaging. MRI contrast agents based on the T2 exchange mechanism have more recently expanded the armamentarium of agents for molecular imaging. Compared with T1 and T2* agents, T2 exchange agents have a slower chemical exchange rate, which improves the ability to design these MRI contrast agents with greater specificity for detecting the intended biomarker. MRI contrast agents that are detected through chemical exchange saturation transfer (CEST) have even slower chemical exchange rates. Another emerging class of MRI contrast agents uses hyperpolarized (13)C to detect the agent with outstanding sensitivity. These hyperpolarized (13)C agents can be used to track metabolism and monitor characteristics of the tissue microenvironment. Together, these various MRI contrast agents provide excellent opportunities to develop molecular imaging for biomarker detection. PMID:27049630

  13. MMP-14 Triggered Fluorescence Contrast Agent.

    PubMed

    Nguyen, Mai-Dung; Kang, Kyung A

    2016-01-01

    Matrix metalloproteinase-14 (MMP-14) is involved in cancer invasion, metastasis, and angiogenesis. Therefore, it is considered to be a biomarker for aggressive cancer types, including some of the triple-negative breast cancer. Accurate (i.e., specific) and sensitive detection of MMP-14 can, thus, be important for the early diagnosis of and accurate prognosis for aggressive cancer, including the breast cancer caused by cell line MDA-MB 231. Fluorophore-mediated molecular sensing has been used for detecting biomarkers, for a long time. One way to increase the specificity of the sensing is designing the fluorophore to emit its fluorescence only when it encounters the biomarker of interest. When a fluorophore is placed on the surface of, or very close to a gold nanoparticle (GNP), its fluorescence is quenched. Applying this relationship between the GNP and fluorophore, we have developed a GNP-based, near-infrared fluorescent contrast agent that is highly specific for MMP-14. This agent normally emits only 14-17 % fluorescence of the free fluorophore. When the agent encounters MMP-14, its fluorescence gets fully restored, allowing MMP-14 specific optical signal emission. PMID:27526171

  14. Gene transfection by echo contrast agent microbubbles

    NASA Astrophysics Data System (ADS)

    Tachibana, Katsuro

    2002-11-01

    In vitro and in vivo experiments have demonstrated that various echo contrast agent microbubbles can be intentionally ruptured by diagnostic and therapeutic ultrasound. Violent microstreaming are produced during microbubble collapse. Researchers have hypothesized that these microjets or microstreaming could be applied to promote diffusion of drugs into various tissues and lesions. The most exciting application of this method is probably delivery of genes into cells. As various genes are currently under investigation for the purpose of treating diseases, ultrasound and microbubbles may be used as a modality to promote better outcome for gene therapy. Recent studies have shown that different gases contained within the bubbles greatly influence the degree of gene transfection. Also, the outer layer of the microbubbles can be custom-made for binding to target tissue. Recent advance on this topic will be discussed.

  15. Intraoperative imaging using intravascular contrast agent

    NASA Astrophysics Data System (ADS)

    Watson, Jeffrey R.; Martirosyan, Nikolay; Garland, Summer; Lemole, G. Michael; Romanowski, Marek

    2016-03-01

    Near-infrared (NIR) contrast agents are becoming more frequently studied in medical imaging due to their advantageous characteristics, most notably the ability to capture near-infrared signal across the tissue and the safety of the technique. This produces a need for imaging technology that can be specific for both the NIR dye and medical application. Indocyanine green (ICG) is currently the primary NIR dye used in neurosurgery. Here we report on using the augmented microscope we described previously for image guidance in a rat glioma resection. Luc-C6 cells were implanted in a rat in the left-frontal lobe and grown for 22 days. Surgical resection was performed by a neurosurgeon using augmented microscopy guidance with ICG contrast. Videos and images were acquired to evaluate image quality and resection margins. ICG accumulated in the tumor tissue due to enhanced permeation and retention from the compromised bloodbrain- barrier. The augmented microscope was capable of guiding the rat glioma resection and intraoperatively highlighted tumor tissue regions via ICG fluorescence under normal illumination of the surgical field.

  16. [Oral magnetic particles as an MR contrast medium for the gastrointestinal tract].

    PubMed

    Rinck, P A; Myhr, G; Smevik, O; Børseth, A

    1992-12-01

    The authors summarise their experience of four clinical studies with a negative oral contrast agent for magnetic resonance imaging of the abdomen and pelvis. 140 patients were enrolled in the studies. These were partly comparative studies pre- and post-contrast, partly at 0.5 and 1.5 T, partly pre-injection and post-injection of glucagon. All patients received 800 ml of a suspension of oral magnetic particles "OMP". The distribution of this contrast agent was homogeneous throughout the entire GI tract. A complete or partial signal void was observed in all patients in T1, T2-, and intermediately weighted images. Generally, diagnostic information was higher after contrast. Artifacts caused by peristalsis and movement of the diaphragm were fewer after contrast. After contrast metallic artifacts were observed in a minority of patients. Adverse events after contrast were minimal; they included nausea and vomiting. PMID:1457787

  17. 21 CFR 872.6030 - Oral cavity abrasive polishing agent.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Oral cavity abrasive polishing agent. 872.6030... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6030 Oral cavity abrasive polishing agent. (a) Identification. An oral cavity abrasive polishing agent is a device in paste or powder...

  18. 21 CFR 872.6030 - Oral cavity abrasive polishing agent.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Oral cavity abrasive polishing agent. 872.6030... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6030 Oral cavity abrasive polishing agent. (a) Identification. An oral cavity abrasive polishing agent is a device in paste or powder...

  19. 21 CFR 872.6030 - Oral cavity abrasive polishing agent.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Oral cavity abrasive polishing agent. 872.6030... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6030 Oral cavity abrasive polishing agent. (a) Identification. An oral cavity abrasive polishing agent is a device in paste or powder...

  20. 21 CFR 872.6030 - Oral cavity abrasive polishing agent.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Oral cavity abrasive polishing agent. 872.6030... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6030 Oral cavity abrasive polishing agent. (a) Identification. An oral cavity abrasive polishing agent is a device in paste or powder...

  1. 21 CFR 872.6030 - Oral cavity abrasive polishing agent.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Oral cavity abrasive polishing agent. 872.6030... (CONTINUED) MEDICAL DEVICES DENTAL DEVICES Miscellaneous Devices § 872.6030 Oral cavity abrasive polishing agent. (a) Identification. An oral cavity abrasive polishing agent is a device in paste or powder...

  2. Tumor-specific fluorescent contrast agents

    NASA Astrophysics Data System (ADS)

    Achilefu, Samuel I.; Dorshow, Richard B.; Bugaj, Joseph E.; Rajagopalan, Raghavan

    2000-04-01

    Several dyes are currently used for various biomedical applications due to their biocompatibility and high molar absorptivity. Localization of dyes in tumors may be mediated by several factors such as leaky vasculature and high metabolic activity in proliferating cells. However, these mechanisms of action make it difficult to differentiate inflammation from benign or malignant tumors. In order to enhance their tumor specificity, dyes have been conjugated to biomolecules that target unique factors in various diseased state. However, such large biomolecules can elicit adverse immunogenic reactions in humans, and are often preferentially taken up by the liver. Furthermore, for solid tumors which may rely on diffusion of the biomarkers from the vascular, penetration of large dye conjugates is not favorable. To overcome these problems, we designed and synthesized novel dye-peptide conjugates that are receptor specific. The efficacy of these new fluorescent contrast agents was tested in vivo in well-characterized rat tumor lines. The resulting optical images demonstrate that successful specific tumor targeting was achieved.

  3. Oral anticancer agent medication adherence by outpatients.

    PubMed

    Kimura, Michio; Usami, Eiseki; Iwai, Mina; Nakao, Toshiya; Yoshimura, Tomoaki; Mori, Hiromi; Sugiyama, Tadashi; Teramachi, Hitomi

    2014-11-01

    In the present study, medication adherence and factors affecting adherence were examined in patients taking oral anticancer agents. In June 2013, 172 outpatients who had been prescribed oral anticancer agents by Ogaki Municipal Hospital (Ogaki, Gifu, Japan) completed a questionnaire survey, with answers rated on a five-point Likert scale. The factors that affect medication adherence were evaluated using a customer satisfaction (CS) analysis. For patients with good and insufficient adherence to medication, the median ages were 66 years (range, 21-85 years) and 73 years (range, 30-90 years), respectively (P=0.0004), while the median dosing time was 131 days (range, 3-3,585 days) and 219 days (24-3,465 days), respectively (P=0.0447). In 36.0% (62 out of 172) of the cases, there was insufficient medication adherence; 64.5% of those cases (40 out of 62) showed good medication compliance (4-5 point rating score). However, these patients did not fully understand the effects or side-effects of the drugs, giving a score of three points or less. The percentage of patients with good medication compliance was 87.2% (150 out of 172). Through the CS analysis, three items, the interest in the drug, the desire to consult about the drug and the condition of the patient, were extracted as items for improvement. Overall, the medication compliance of the patients taking the oral anticancer agents was good, but the medication adherence was insufficient. To improve medication adherence, a better understanding of the effectiveness and necessity of drugs and their side-effects is required. In addition, the interest of patients in their medication should be encouraged and intervention should be tailored to the condition of the patient. These steps should lead to improved medication adherence. PMID:25295117

  4. Oral anticancer agent medication adherence by outpatients

    PubMed Central

    KIMURA, MICHIO; USAMI, EISEKI; IWAI, MINA; NAKAO, TOSHIYA; YOSHIMURA, TOMOAKI; MORI, HIROMI; SUGIYAMA, TADASHI; TERAMACHI, HITOMI

    2014-01-01

    In the present study, medication adherence and factors affecting adherence were examined in patients taking oral anticancer agents. In June 2013, 172 outpatients who had been prescribed oral anticancer agents by Ogaki Municipal Hospital (Ogaki, Gifu, Japan) completed a questionnaire survey, with answers rated on a five-point Likert scale. The factors that affect medication adherence were evaluated using a customer satisfaction (CS) analysis. For patients with good and insufficient adherence to medication, the median ages were 66 years (range, 21–85 years) and 73 years (range, 30–90 years), respectively (P=0.0004), while the median dosing time was 131 days (range, 3–3,585 days) and 219 days (24–3,465 days), respectively (P=0.0447). In 36.0% (62 out of 172) of the cases, there was insufficient medication adherence; 64.5% of those cases (40 out of 62) showed good medication compliance (4–5 point rating score). However, these patients did not fully understand the effects or side-effects of the drugs, giving a score of three points or less. The percentage of patients with good medication compliance was 87.2% (150 out of 172). Through the CS analysis, three items, the interest in the drug, the desire to consult about the drug and the condition of the patient, were extracted as items for improvement. Overall, the medication compliance of the patients taking the oral anticancer agents was good, but the medication adherence was insufficient. To improve medication adherence, a better understanding of the effectiveness and necessity of drugs and their side-effects is required. In addition, the interest of patients in their medication should be encouraged and intervention should be tailored to the condition of the patient. These steps should lead to improved medication adherence. PMID:25295117

  5. Nanoparticle Contrast Agents for Computed Tomography: A Focus on Micelles

    PubMed Central

    Cormode, David P.; Naha, Pratap C.; Fayad, Zahi A.

    2014-01-01

    Computed tomography (CT) is an X-ray based whole body imaging technique that is widely used in medicine. Clinically approved contrast agents for CT are iodinated small molecules or barium suspensions. Over the past seven years there has been a great increase in the development of nanoparticles as CT contrast agents. Nanoparticles have several advantages over small molecule CT contrast agents, such as long blood-pool residence times, and the potential for cell tracking and targeted imaging applications. Furthermore, there is a need for novel CT contrast agents, due to the growing population of renally impaired patients and patients hypersensitive to iodinated contrast. Micelles and lipoproteins, a micelle-related class of nanoparticle, have notably been adapted as CT contrast agents. In this review we discuss the principles of CT image formation and the generation of CT contrast. We discuss the progress in developing non-targeted, targeted and cell tracking nanoparticle CT contrast agents. We feature agents based on micelles and used in conjunction with spectral CT. The large contrast agent doses needed will necessitate careful toxicology studies prior to clinical translation. However, the field has seen tremendous advances in the past decade and we expect many more advances to come in the next decade. PMID:24470293

  6. [Iodinated contrast agents used in Radiology].

    PubMed

    Ramírez Ribelles, C; Sánchez Fuster, M A; Pamies Guilabert, J

    2014-06-01

    Iodinated contrast media are widely used in Radiology practices with a very low rate of adverse effects, being contrast-induced nephropathy the most serious one. In the majority of cases it is temporary and reversible, even though it can increase the inhospital morbidity and mortality in patients with risk factors. We will describe the various measures of prevention, being hydration and use of non-ionic contrast low osmolality those which have demonstrated greater effectiveness. Precautions to be taken in some risk situations, as patients treated with metformin or with impaired renal function, are also discussed. PMID:25267147

  7. Modified natural nanoparticles as contrast agents for medical imaging

    PubMed Central

    Cormode, David P.; Jarzyna, Peter A.; Mulder, Willem J. M.; Fayad, Zahi A.

    2009-01-01

    The development of novel and effective contrast agents is one of the drivers of the ongoing improvement in medical imaging. Many of the new agents reported are nanoparticle-based. There are a variety of natural nanoparticles known, e.g. lipoproteins, viruses or ferritin. Natural nanoparticles have advantages as delivery platforms such as biodegradability. In addition, our understanding of natural nanoparticles is quite advanced, allowing their adaptation as contrast agents. They can be labeled with small molecules or ions such as Gd3+ to act as contrast agents for magnetic resonance imaging, 18F to act as positron emission tomography contrast agents or fluorophores to act as contrast agents for fluorescence techniques. Additionally, inorganic nanoparticles such as iron oxide, gold nanoparticles or quantum dots can be incorporated to add further contrast functionality. Furthermore, these natural nanoparticle contrast agents can be rerouted from their natural targets via the attachment of targeting molecules. In this review, we discuss the various modified natural nanoparticles that have been exploited as contrast agents. PMID:19900496

  8. Basic MR relaxation mechanisms and contrast agent design.

    PubMed

    De León-Rodríguez, Luis M; Martins, André F; Pinho, Marco C; Rofsky, Neil M; Sherry, A Dean

    2015-09-01

    The diagnostic capabilities of magnetic resonance imaging (MRI) have undergone continuous and substantial evolution by virtue of hardware and software innovations and the development and implementation of exogenous contrast media. Thirty years since the first MRI contrast agent was approved for clinical use, a reliance on MR contrast media persists, largely to improve image quality with higher contrast resolution and to provide additional functional characterization of normal and abnormal tissues. Further development of MR contrast media is an important component in the quest for continued augmentation of diagnostic capabilities. In this review we detail the many important considerations when pursuing the design and use of MR contrast media. We offer a perspective on the importance of chemical stability, particularly kinetic stability, and how this influences one's thinking about the safety of metal-ligand-based contrast agents. We discuss the mechanisms involved in MR relaxation in the context of probe design strategies. A brief description of currently available contrast agents is accompanied by an in-depth discussion that highlights promising MRI contrast agents in the development of future clinical and research applications. Our intention is to give a diverse audience an improved understanding of the factors involved in developing new types of safe and highly efficient MR contrast agents and, at the same time, provide an appreciation of the insights into physiology and disease that newer types of responsive agents can provide. PMID:25975847

  9. Inorganic nanoparticle-based contrast agents for molecular imaging

    PubMed Central

    Cho, Eun Chul; Glaus, Charles; Chen, Jingyi; Welch, Michael J.; Xia, Younan

    2010-01-01

    Inorganic nanoparticles including semiconductor quantum dots, iron oxide nanoparticles, and gold nanoparticles have been developed as contrast agents for diagnostics by molecular imaging. Compared to traditional contrast agents, nanoparticles offer several advantages: their optical and magnetic properties can be tailored by engineering the composition, structure, size, and shape; their surfaces can be modified with ligands to target specific biomarkers of disease; the contrast enhancement provided can be equivalent to millions of molecular counterparts; and they can be integrated with a combination of different functions for multi-modal imaging. Here, we review recent advances in the development of contrast agents based on inorganic nanoparticles for molecular imaging, with a touch on contrast enhancement, surface modification, tissue targeting, clearance, and toxicity. As research efforts intensify, contrast agents based on inorganic nanoparticles that are highly sensitive, target-specific, and safe to use are expected to enter clinical applications in the near future. PMID:21074494

  10. Biodegradable Iodinated Polydisulfides as Contrast Agents for CT Angiography

    PubMed Central

    Jin, Erlei; Zheng-Rong, Lu

    2014-01-01

    Current clinical CT contrast agents are mainly small molecular iodinated compounds, which often suffer from short blood pool retention for more comprehensive cardiovascular CT imaging and may cause contrast-induced nephropathy. In this work, we prepared polydisulfides containing a traditional iodinated CT contrast agent in order to optimize the pharmacokinetics of the agent and improve its safety. Initially acting as a macromolecular agent and achieving sharp blood vessel delineation, the polydisulfides can be reduced by endogenous thiols via disulfide-thiol exchange reaction to oligomers that can be readily excreted via renal filtration. Short polyethylene glycol (PEG) chain was also introduced to the polymers to further modify the in vivo properties of the agents. Strong and prolonged vascular enhancement has been generated with two new agents in mice (5–10 times higher blood pool enhancement than iodinaxol). The polydisulfide agents gradually degraded and excreted via renal filtration. The gradual excretion process could prevent contrast induced nephropathy. These results suggest that the biodegradable macromolecular CT contrast agents are promising safe and effective blood contrast agents for CT angiography and image-guided interventions. PMID:24768156

  11. Non-toxic lead sulfide nanodots as efficient contrast agents for visualizing gastrointestinal tract.

    PubMed

    Liu, Zhen; Ran, Xiang; Liu, Jianhua; Du, Yingda; Ren, Jinsong; Qu, Xiaogang

    2016-09-01

    Non-invasive imaging of gastrointestinal (GI) tract using novel but efficient contrast agents is of the most important issues in the diagnosis and prognosis of GI diseases. Here, for the first time, we reported the design and synthesis of biothiol-decorated lead sulfide nanodots, as well as their usages in functional dual-modality imaging of GI tract in vivo. Due to the presence of glutathione on the surface of the nanodots, these well-prepared contrast agents could decrease the unwanted ion leakage, withstand the harsh conditions in GI tract, and avoid the systemic absorption after oral administration. Compared with clinical barium meal and iodine-based contrast agents, these nanodots exhibited much more significant enhancement in contrast efficiency during both 2D X-ray imaging and 3D CT imaging. Different from some conventional invasive imaging modalities, such as gastroscope and enteroscope, non-invasive imaging strategy by using glutathione modified PbS nanodots as contrast agents could reduce the painfulness towards patients, facilitate the imaging procedure, and economize the manipulation period. Moreover, long-term toxicity and bio-distribution of these nanodots after oral administration were evaluated in detail, which indicated their overall safety. Based on our present study, these nanodots could act as admirable contrast agents to integrate X-ray imaging and CT imaging for the direct visualization of GI tract. PMID:27240159

  12. Contrast agents in diagnostic imaging: Present and future.

    PubMed

    Caschera, Luca; Lazzara, Angelo; Piergallini, Lorenzo; Ricci, Domenico; Tuscano, Bruno; Vanzulli, Angelo

    2016-08-01

    Specific contrast agents have been developed for x ray examinations (mainly CT), sonography and Magnetic Resonance Imaging. Most of them are extracellular agents which create different enhancement on basis of different vascularization or on basis of different interstitial network in tissues, but some can be targeted to a particular cell line (e.g. hepatocyte). Microbubbles can be used as carrier for therapeutic drugs which can be released in specific targets under sonographic guidance, decreasing systemic toxicity and increasing therapeutic effect. Radiologists have to choose a particular contrast agent knowing its physical and chemical properties and the possibility of adverse reactions and balancing them with the clinical benefits of a more accurate diagnosis. As for any drug, contrast agents can cause adverse events, which are more frequent with Iodine based CA, but also with Gd based CA and even with sonographic contrast agents hypersensitivity reaction can occur. PMID:27168225

  13. Superparamagnetic nanoparticle-inclusion microbubbles for ultrasound contrast agents

    NASA Astrophysics Data System (ADS)

    Yang, Fang; Li, Ling; Li, Yixin; Chen, Zhongping; Wu, Junru; Gu, Ning

    2008-11-01

    We have developed a new type of ultrasound (US) contrast agent, consisting of a gas core, a layer of superparamagnetic iron oxide Fe3O4 nanoparticles (SPIO) and an oil in water outermost layer. The newly developed US contrast agent microbubbles have a mean diameter of 760 nm with a polydisperity index (PI) of 0.699. Our in vitro and in vivo experiments have shown that they have the following advantages compared to gas-encapsulated microbbubbles without SPIO inclusion: (1) they provide better contrast for US images; (2) the SPIO-inclusion microbubbles generate a higher backscattering signal; the mean grey scale is 97.9, which is 38.6 higher than that of microbubbles without SPIO; and (3) since SPIO can also serve as a contrast agent of magnetic resonance images (MRI) in vitro, they can be potentially used as contrast agents for double-modality (MRI and US) clinical studies.

  14. [Mecanisms of pharmacokinetic interactions involving oral anticancer agents].

    PubMed

    Levêque, Dominique; Duval, Céline; Poulat, Charlotte; Palas, Benjamin; El Aatmani, Anne; Dory, Anne; Becker, Guillaume; Gourieux, Bénédicte

    2015-01-01

    Oral anticancer agents and particularly kinase inhibitors are subject to pharmacokinetic drug interactions in relation to absorption and elimination phases. Interacting factors are food, fruit juices, cigarette smoke, acid-reducing agents and inducers/inhibitors. Some anticancer agents are inducers and/or inhibitors and can also perpetrate drug interactions. This review emphasizes the mechanisms of pharmacokinetic drug interactions involving oral anticancer agents. PMID:25609481

  15. Iron Oxide as an MRI Contrast Agent for Cell Tracking

    PubMed Central

    Korchinski, Daniel J.; Taha, May; Yang, Runze; Nathoo, Nabeela; Dunn, Jeff F.

    2015-01-01

    Iron oxide contrast agents have been combined with magnetic resonance imaging for cell tracking. In this review, we discuss coating properties and provide an overview of ex vivo and in vivo labeling of different cell types, including stem cells, red blood cells, and monocytes/macrophages. Furthermore, we provide examples of applications of cell tracking with iron contrast agents in stroke, multiple sclerosis, cancer, arteriovenous malformations, and aortic and cerebral aneurysms. Attempts at quantifying iron oxide concentrations and other vascular properties are examined. We advise on designing studies using iron contrast agents including methods for validation. PMID:26483609

  16. Microbubbles as contrast agent for in-line x-ray phase-contrast imaging

    SciTech Connect

    Xi Yan; Zhao Jun; Tang Rongbiao; Wang Yujie

    2011-07-04

    In the present study, we investigated the potential of gas-filled microbubbles as contrast agents for in-line x-ray phase-contrast imaging (PCI) in biomedical applications. When imaging parameters are optimized, the microbubbles function as microlenses that focus the incoming x-rays to form bright spots, which can significantly enhance the image contrast. Since microbubbles have been shown to be safe contrast agents in clinical ultrasonography, this contrast-enhancement procedure for PCI may have promising utility in biomedical applications, especially when the dose of radiation is a serious concern. In this study, we performed both numerical simulations and ex vivo experiments to investigate the formation of the contrast and the effectiveness of microbubbles as contrast agents in PCI.

  17. Improvement of distension and mural visualization of bowel loops using neutral oral contrasts in abdominal computed tomography

    PubMed Central

    Hashemi, Jahanbakhsh; Davoudi, Yasmin; Taghavi, Mina; Pezeshki Rad, Masoud; Moghadam, Amien Mahajeri

    2014-01-01

    AIM: To assess and compare the image quality of 4% sorbitol and diluted iodine 2% (positive oral contrast agent) in abdomino-pelvic multi-detector computed tomography. METHODS: Two-hundred patients, referred to the Radiology Department of a central educational hospital for multi-detector row abdominal-pelvic computed tomography, were randomly divided into two groups: the first group received 1500 mL of 4% sorbitol solution as a neutral contrast agent, while in the second group 1500 mL of meglumin solution as a positive contrast agent was administered in a one-way randomized prospective study. The results were independently reviewed by two radiologists. Luminal distension and mural thickness and mucosal enhancement were compared between the two groups. Statistical analysis of the results was performed by Statistical Package for the Social Sciences software version 16 and the Mann-Whitney test at a confidence level of 95%. RESULTS: Use of neutral oral contrast agent significantly improved visualization of the small bowel wall thickness and mural appearance in comparison with administration of positive contrast agent (P < 0.01). In patients who received sorbitol, the small bowel showed better distention compared with those who received iodine solution as a positive contrast agent (P < 0.05). CONCLUSION: The results of the study demonstrated that oral administration of sorbitol solution allows better luminal distention and visualization of mural features than iodine solution as a positive contrast agent. PMID:25550995

  18. A brief account of nanoparticle contrast agents for photoacoustic imaging.

    PubMed

    Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V; Lanza, Gregory M

    2013-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds. PMID:23983210

  19. MRI contrast agent concentration and tumor interstitial fluid pressure.

    PubMed

    Liu, L J; Schlesinger, M

    2016-10-01

    The present work describes the relationship between tumor interstitial fluid pressure (TIFP) and the concentration of contrast agent for dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI). We predict the spatial distribution of TIFP based on that of contrast agent concentration. We also discuss the cases for estimating tumor interstitial volume fraction (void fraction or porosity of porous medium), ve, and contrast volume transfer constant, K(trans), by measuring the ratio of contrast agent concentration in tissue to that in plasma. A linear fluid velocity distribution may reflect a quadratic function of TIFP distribution and lead to a practical method for TIFP estimation. To calculate TIFP, the parameters or variables should preferably be measured along the direction of the linear fluid velocity (this is in the same direction as the gray value distribution of the image, which is also linear). This method may simplify the calculation for estimating TIFP. PMID:27343032

  20. A Brief Account of Nanoparticle Contrast Agents for Photoacoustic Imaging

    PubMed Central

    Pan, Dipanjan; Kim, Benjamin; Wang, Lihong V.; Lanza, Gregory M

    2014-01-01

    Photoacoustic imaging (PAI) is a hybrid, nonionizing modality offering excellent spatial resolution, deep penetration, and high soft tissue contrast. In PAI, signal is generated based on the absorption of laser-generated optical energy by endogenous tissues or exogenous contrast agents leading to acoustic emissions detected by an ultrasound transducer. Research in this area over the years has shown that PAI has the ability to provide both physiological and molecular imaging, which can be viewed alone or used in a hybrid modality fashion to extend the anatomic and hemodynamic sensitivities of clinical ultrasound. PAI may be performed using inherent contrast afforded by light absorbing molecules such as hemoglobin, myoglobin, and melanin or exogenous small molecule contrast agent such as near infrared dyes and porphyrins. However, this review summarizes the potential of exogenous nanoparticle-based agents for PAI applications including contrast based on gold particles, carbon nanotubes, and encapsulated copper compounds. PMID:23983210

  1. Multiwalled carbon nanotube hybrids as MRI contrast agents.

    PubMed

    Kuźnik, Nikodem; Tomczyk, Mateusz Michał

    2016-01-01

    Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories. PMID:27547627

  2. Multiwalled carbon nanotube hybrids as MRI contrast agents

    PubMed Central

    Tomczyk, Mateusz Michał

    2016-01-01

    Summary Magnetic resonance imaging (MRI) is one of the most commonly used tomography techniques in medical diagnosis due to the non-invasive character, the high spatial resolution and the possibility of soft tissue imaging. Contrast agents, such as gadolinium complexes and superparamagnetic iron oxides, are administered to spotlight certain organs and their pathologies. Many new models have been proposed that reduce side effects and required doses of these already clinically approved contrast agents. These new candidates often possess additional functionalities, e.g., the possibility of bioactivation upon action of particular stimuli, thus serving as smart molecular probes, or the coupling with therapeutic agents and therefore combining both a diagnostic and therapeutic role. Nanomaterials have been found to be an excellent scaffold for contrast agents, among which carbon nanotubes offer vast possibilities. The morphology of multiwalled carbon nanotubes (MWCNTs), their magnetic and electronic properties, the possibility of different functionalization and the potential to penetrate cell membranes result in a unique and very attractive candidate for a new MRI contrast agent. In this review we describe the different issues connected with MWCNT hybrids designed for MRI contrast agents, i.e., their synthesis and magnetic and dispersion properties, as well as both in vitro and in vivo behavior, which is important for diagnostic purposes. An introduction to MRI contrast agent theory is elaborated here in order to point to the specific expectations regarding nanomaterials. Finally, we propose a promising, general model of MWCNTs as MRI contrast agent candidates based on the studies presented here and supported by appropriate theories. PMID:27547627

  3. Gadolinium-Based Contrast Agent Accumulation and Toxicity: An Update.

    PubMed

    Ramalho, J; Semelka, R C; Ramalho, M; Nunes, R H; AlObaidy, M; Castillo, M

    2016-07-01

    In current practice, gadolinium-based contrast agents have been considered safe when used at clinically recommended doses in patients without severe renal insufficiency. The causal relationship between gadolinium-based contrast agents and nephrogenic systemic fibrosis in patients with renal insufficiency resulted in new policies regarding the administration of these agents. After an effective screening of patients with renal disease by performing either unenhanced or reduced-dose-enhanced studies in these patients and by using the most stable contrast agents, nephrogenic systemic fibrosis has been largely eliminated since 2009. Evidence of in vivo gadolinium deposition in bone tissue in patients with normal renal function is well-established, but recent literature showing that gadolinium might also deposit in the brain in patients with intact blood-brain barriers caught many individuals in the imaging community by surprise. The purpose of this review was to summarize the literature on gadolinium-based contrast agents, tying together information on agent stability and animal and human studies, and to emphasize that low-stability agents are the ones most often associated with brain deposition. PMID:26659341

  4. Optical characterization of contrast agents for optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Lee, Tin-Man; Toublan, Farah J.; Oldenburg, Amy; Sitafalwalla, Shoeb; Luo, Wei; Marks, Daniel L.; Suslick, Kenneth S.; Boppart, Stephen A.

    2003-07-01

    The use of contrast agents in almost every imaging modality has been known to enhance the sensitivity of detection and improve diagnostic capabilities by site-specifically labeling tissues or cells of interest. The imaging capabilities of Optical Coherence Tomography (OCT) need to be improved in order to detect early neoplastic changes in medicine and tumor biology. We introduce and characterize the optical properties of several types of optical contrast agents in OCT, namely encapsulating microspheres that incorporate materials including melanin, gold, and carbon. Micron-sized microspheres have been fabricated by state-of-the-art sonicating and ultrasound technology. The optical properties of optical contrast agents have been characterized according to their scattering and absorption coefficients and lifetimes using OCT and the oblique incidence reflectometry method. Finally, we demonstrate the use of these optical contrast agents in in vitro mice liver and analyze the contrast improvement from the OCT images. These optical contrast agents have the potential to improve the detection of in vivo pathologies in the future.

  5. Targeting cancer chemotherapeutic agents by use of lipiodol contrast medium

    SciTech Connect

    Konno, T. )

    1990-11-01

    Arterially administered Lipiodol Ultrafluid contrast medium selectively remained in various malignant solid tumors because of the difference in time required for the removal of Lipiodol contrast medium from normal capillaries and tumor neovasculature. Although blood flow was maintained in the tumor, even immediately after injection Lipiodol contrast medium remained in the neovasculature of the tumor. To target anti-cancer agents to tumors by using Lipiodol contrast medium as a carrier, the characteristics of the agents were examined. Anti-cancer agents had to be soluble in Lipiodol, be stable in it, and separate gradually from it so that the anti-cancer agents would selectively remain in the tumor. These conditions were found to be necessary on the basis of the measurement of radioactivity in VX2 tumors implanted in the liver of 16 rabbits that received arterial injections of 14C-labeled doxorubicin. Antitumor activities and side effects of arterial injections of two types of anti-cancer agents were compared in 76 rabbits with VX2 tumors. Oily anti-cancer agents that had characteristics essential for targeting were compared with simple mixtures of anti-cancer agents with Lipiodol contrast medium that did not have these essential characteristics. Groups of rabbits that received oily anti-cancer agents responded significantly better than groups that received simple mixtures, and side effects were observed more frequently in the groups that received the simple mixtures. These results suggest that targeting of the anti-cancer agent to the tumor is important for treatment of solid malignant tumors.

  6. Chlorotoxin-modified macromolecular contrast agent for MRI tumor diagnosis.

    PubMed

    Huang, Rongqin; Han, Liang; Li, Jianfeng; Liu, Shuhuan; Shao, Kun; Kuang, Yuyang; Hu, Xing; Wang, Xuxia; Lei, Hao; Jiang, Chen

    2011-08-01

    Clinical diagnosis of cancers using magnetic resonance imaging (MRI) is highly dependent on contrast agents, especially for brain tumors which contain blood-brain barrier (BBB) at the early stage. However, currently mostly used low molecular weight contrast agents such as Gd-DTPA suffer from rapid renal clearance, non-specificity, and low contrast efficiency. The aim of this paper is to investigate the potential of a macromolecular MRI contrast agent based on dendrigraft poly-l-lysines (DGLs), using chlorotoxin (CTX) as a tumor-specific ligand. The contrast agent using CTX-modified conjugate as the main scaffold and Gd-DTPA as the payload was successfully synthesized. The results of fluorescent microscopy showed that the modification of CTX could markedly enhance the cellular uptake in C6 glioma and liver tumor cell lines, but not in normal cell line. Significantly increased accumulation of CTX-modified conjugate within glioma and liver tumor was further demonstrated in tumor-bearing nude mice using in vivo imaging system. The MRI results showed that the signal enhancement of mice treated with CTX-modified contrast reached peak level at 5 min for both glioma and liver tumor, 144.97% ± 19.54% and 158.69% ± 12.41%, respectively, significantly higher than that of unmodified counterpart and commercial control. And most importantly, the signal enhancement of CTX-modified contrast agent maintained much longer compared to that of controls, which might be useful for more exact diagnosis for tumors. CTX-modified dendrimer-based conjugate might be applied as an efficient MRI contrast agent for targeted and accurate tumor diagnosis. This finding is especially important for tumors such as brain glioma which is known hard to be diagnosed due to the presence of BBB. PMID:21531455

  7. Efficient mucosal delivery of optical contrast agents using imidazole-modified chitosan

    NASA Astrophysics Data System (ADS)

    Ghosn, Bilal; van de Ven, Anne L.; Tam, Justina; Gillenwater, Ann; Sokolov, Konstantin V.; Richards-Kortum, Rebecca; Roy, Krishnendu

    2010-01-01

    The clinical applicability of antibodies and plasmonic nanosensors as topically applied, molecule-specific optical diagnostic agents for noninvasive early detection of cancer and precancer is severely limited by our inability to efficiently deliver macromolecules and nanoparticles through mucosal tissues. We have developed an imidazole-functionalized conjugate of the polysaccharide chitosan (chitosan-IAA) to enhance topical delivery of contrast agents, ranging from small molecules and antibodies to gold nanoparticles up to 44 nm in average diameter. Contrast agent uptake and localization in freshly resected mucosal tissues was monitored using confocal microscopy. Chitosan-IAA was found to reversibly enhance mucosal permeability in a rapid, reproducible manner, facilitating transepithelial delivery of optical contrast agents. Permeation enhancement occurred through an active process, resulting in the delivery of contrast agents via a paracellular or a combined paracellular/transcellular route depending on size. Coadministration of epidermal growth factor receptor-targeted antibodies with chitosan-IAA facilitated specific labeling and discrimination between paired normal and malignant human oral biopsies. Together, these data suggest that chitosan-IAA is a promising topical permeation enhancer for mucosal delivery of optical contrast agents.

  8. Pineapple juice labeled with gadolinium: a convenient oral contrast for magnetic resonance cholangiopancreatography.

    PubMed

    Coppens, Emmanuel; Metens, Thierry; Winant, Catherine; Matos, Celso

    2005-10-01

    The aim of our study was to prepare in vitro a pineapple juice (PJ) solution labeled with a minimal gadolinium concentration working as a negative contrast agent in heavily T2-weighted imaging and to assess that solution in vivo as a negative oral contrast agent for magnetic resonance cholangiopancreatography (MRCP). Three PJs were compared in vitro according to their T2. Increasing concentrations of gadolinium (Gd)-DOTA in PJ were assessed in vitro for T2 reduction. Single-shot turbo spin echo T2-weighted MR cholangiopancreatograms were obtained for 35 patients with suspected biliopancreatic duct disease, before and after ingestion of the PJ/Gd-DOTA solution. Signal intensity (SI) measurements of gastroduodenal lumens, pancreatobiliary ducts, and image quality scores were obtained systematically before and after contrast ingestion. The in vitro selected Gd-DOTA concentration in the PJ was 2.76 mmol/l. Ingestion of 180 ml of PJ labeled with 1 ml of Gd-DOTA eliminated efficiently the gastroduodenal SI in MRCP, improving significantly the rates of complete visualization of the pancreatobiliary ducts (P<0.01) and the MRCP image quality scores (P<0.05). All patients easily ingested the contrast solution and found the solution palatable. PJ labeled with gadolinium constituted an efficient and convenient negative oral contrast agent for MRCP. PMID:15999215

  9. Contrast Agents for Photoacoustic and Thermoacoustic Imaging: A Review

    PubMed Central

    Wu, Dan; Huang, Lin; Jiang, Max S.; Jiang, Huabei

    2014-01-01

    Photoacoustic imaging (PAI) and thermoacoustic imaging (TAI) are two emerging biomedical imaging techniques that both utilize ultrasonic signals as an information carrier. Unique advantages of PAI and TAI are their abilities to provide high resolution functional information such as hemoglobin and blood oxygenation and tissue dielectric properties relevant to physiology and pathology. These two methods, however, may have a limited detection depth and lack of endogenous contrast. An exogenous contrast agent is often needed to effectively resolve these problems. Such agents are able to greatly enhance the imaging contrast and potentially break through the imaging depth limit. Furthermore, a receptor-targeted contrast agent could trace the molecular and cellular biological processes in tissues. Thus, photoacoustic and thermoacoustic molecular imaging can be outstanding tools for early diagnosis, precise lesion localization, and molecular typing of various diseases. The agents also could be used for therapy in conjugation with drugs or in photothermal therapy, where it functions as an enhancer for the integration of diagnosis and therapy. In this article, we present a detailed review about various exogenous contrast agents for photoacoustic and thermoacoustic molecular imaging. In addition, challenges and future directions of photoacoustic and thermoacoustic molecular imaging in the field of translational medicine are also discussed. PMID:25530615

  10. Selective imaging of adherent targeted ultrasound contrast agents

    PubMed Central

    Zhao, S; Kruse, D E; Ferrara, K W; Dayton, P A

    2007-01-01

    The goal of ultrasonic molecular imaging is the detection of targeted contrast agents bound to receptors on endothelial cells. We propose imaging methods that can distinguish adherent microbubbles from tissue and from freely circulating microbubbles, each of which would otherwise obscure signal from molecularly targeted adherent agents. The methods are based on a harmonic signal model of the returned echoes over a train of pulses. The first method utilizes an ‘image–push–image’ pulse sequence where adhesion of contrast agents is rapidly promoted by acoustic radiation force and the presence of adherent agents is detected by the signal change due to targeted microbubble adhesion. The second method rejects tissue echoes using a spectral high-pass filter. Free agent signal is suppressed by a pulse-to-pulse low-pass filter in both methods. An overlay of the adherent and/or flowing contrast agents on B-mode images can be readily created for anatomical reference. Contrast-to-tissue ratios from adherent microbubbles exceeding 30 dB and 20 dB were achieved for the two methods proposed, respectively. The performance of these algorithms is compared, emphasizing the significance and potential applications in ultrasonic molecular imaging. PMID:17404455

  11. Exogenous contrast agents for thermoacoustic imaging: An investigation into the underlying sources of contrast

    SciTech Connect

    Ogunlade, Olumide Beard, Paul

    2015-01-15

    Purpose: Thermoacoustic imaging at microwave excitation frequencies is limited by the low differential contrast exhibited by high water content tissues. To overcome this, exogenous thermoacoustic contrast agents based on gadolinium compounds, iron oxide, and single wall carbon nanotubes have previously been suggested and investigated. However, these previous studies did not fully characterize the electric, magnetic, and thermodynamic properties of these agents thus precluding identification of the underlying sources of contrast. To address this, measurements of the complex permittivity, complex permeability, DC conductivity, and Grüneisen parameter have been made. These measurements allowed the origins of the contrast provided by each substance to be identified. Methods: The electric and magnetic properties of the contrast agents were characterized at 3 GHz using two rectangular waveguide cavities. The DC conductivity was measured separately using a conductivity meter. Thermoacoustic signals were then acquired and compared to those generated in water. Finally, 3D electromagnetic simulations were used to decouple the different contributions to the absorbed power density. Results: It was found that the gadolinium compounds provided appreciable electric contrast but not originating from the gadolinium itself. The contrast was either due to dissociation of the gadolinium salt which increased ionic conductivity or its nondissociated polar fraction which increased dielectric polarization loss or a combination of both. In addition, very high concentrations were required to achieve appreciable contrast, to the extent that the Grüneisen parameter increased significantly and became a source of contrast. Iron oxide particles were found to produce low but measurable dielectric contrast due to dielectric polarization loss, but this is attributed to the coating of the particles not the iron oxide. Single wall carbon nanotubes did not provide measurable contrast of any type

  12. Use of pineapple juice with gadopentetate dimeglumine as a negative oral contrast for magnetic resonance cholangiopancreatography: a multicentric study.

    PubMed

    Duarte, Juliana Avila; Furtado, Alvaro Porto Alegre; Marroni, Claudio Augusto

    2012-06-01

    We evaluated the efficacy of pineapple juice with gadopentetate dimeglumine as a negative oral contrast agent for magnetic resonance cholangiopancreatography (MRCP). Images were obtained before and after the intake of a negative oral contrast agent. Images obtained from six different areas of the biliary tree were analyzed by three different radiologists, who were blind to the exams; scores regarding image quality were given to each area. The statistical analysis showed a significant difference between images before and after the use of the contrast agent (P < 0.001) for the three radiologists (R1-R3). Mean scores given by radiologists before the intake of the contrast agent were 2.49 ± 0.42 (R1), 2.62 ± 0.32 (R2), and 2.22 ± 0.46 (R3). After the intake, mean scores were 3.38 ± 0.62 (R1), 3.48 ± 0.55 (R2), and 2.89 ± 0.69 (R3). The ducts that showed the highest scores were the common bile duct and duct of Wirsung, the distal portion of the common bile duct and the cystic duct. We suggest herein that the contrast agent pineapple juice with gadopentate dimeglumine constitutes an efficient negative oral contrast agent for MRCP, for it efficiently eliminates the signal of the digestive tube in MRCP images. PMID:21630051

  13. Graphene-based contrast agents for photoacoustic and thermoacoustic tomography☆

    PubMed Central

    Lalwani, Gaurav; Cai, Xin; Nie, Liming; Wang, Lihong V.; Sitharaman, Balaji

    2013-01-01

    In this work, graphene nanoribbons and nanoplatelets were investigated as contrast agents for photoacoustic and thermoacoustic tomography (PAT and TAT). We show that oxidized single- and multi-walled graphene oxide nanoribbons (O-SWGNRs, O-MWGNRs) exhibit approximately 5–10 fold signal enhancement for PAT in comparison to blood at the wavelength of 755 nm, and approximately 10–28% signal enhancement for TAT in comparison to deionized (DI) water at 3 GHz. Oxidized graphite microparticles (O-GMPs) and exfoliated graphene oxide nanoplatelets (O-GNPs) show no significant signal enhancement for PAT, and approximately 12–29% signal enhancement for TAT. These results indicate that O-GNRs show promise as multi-modal PAT and TAT contrast agents, and that O-GNPs are suitable contrast agents for TAT. PMID:24490141

  14. Oral Adverse Reactions Caused by Over-the-Counter Oral Agents

    PubMed Central

    Andabak Rogulj, Ana; Vidovic Juras, Danica; Gabric, Dragana; Vrdoljak, Danko Velimir

    2015-01-01

    Over-the-counter products rarely cause unwanted reactions in the oral cavity. Oral reactions to these agents are not specific and might present with various clinical oral findings. Detailed medical history is a key to the proper diagnosis of these lesions and fortunately other diagnostic procedures are rarely needed. Lesions are usually managed with elimination of the offending agent and with topical steroids. In more severe cases systemic steroids should be applied. PMID:25883811

  15. Ultrasound contrast agents and their use in monitoring therapy

    NASA Astrophysics Data System (ADS)

    Ferrara, Katherine; Dayton, Paul; Shortencarrier, Michaelann; Kruse, Dustin

    2003-10-01

    The shell of ultrasound contrast agents can be modified to include a molecular targeting ligand, and the properties of the agent with and without molecular targeting can be used to monitor changes produced by a therapy. We have investigated the use of ligands targeted to an integrin expressed in cancer, whose expression correlates with tumor grade. Acoustic studies illustrate a 3- to 20-fold increase in echo amplitude from integrin-expressing cells exposed to the targeted contrast agent, as compared to controls, and depending on cell type, stimulation, and targeting ligand. Changes in integrin expression with therapy may be important in future studies. We have also developed a system to quantify small changes in vascular parameters due to effects of new anti-angiogenic drugs using the intrinsic properties of contrast agents. Regions containing intravascular contrast agents are identified using a strategy that combines subharmonic and phase inversion imaging. As predicted by a Rayleigh-Plesset analysis, this strategy can successfully detect flow over a range of transmission frequencies from 4-6 MHz. We demonstrate that regions of viable tumor as small as 1 mm, as verified by histology, can be detected and show similar morphology to images acquired with computed tomography (CT).

  16. Influence of radiographic contrast agents on quantitative coronary angiography

    SciTech Connect

    Jost, Stefan; Hausmann, Dirk; Lippolt, Peter; Gerhardt, Uwe; Lichtlen, Paul R.

    1997-01-15

    Purpose. Quantitative angiographic studies on the vasomotility of epicardial coronary arteries are gaining increasing relevance. We investigated whether radiographic contrast agents might influence coronary vasomotor tone and thereby the results of such studies. Methods. Coronary angiograms were taken in 12 patients with coronary artery disease at intervals of 5, 3, 2, and 1 min with the low-osmolar, nonionic contrast agent iopamidol 300, and were repeated at identical intervals with the high-osmolar, ionic agent diatrizoate 76%. Results. Quantitative cine film analysis demonstrated no significant diameter changes in angiographically normal and stenotic coronary arteries with iopamidol. With diatrizoate, however, normal segments were dilated 2%{+-}2% (p<0.01) after 2 min and 10%{+-}3% after the 1 min interval (p<0.001). Stenoses showed no uniform responses to diatrizoate. Conclusion. Low-osmolar, nonionic contrast agents should be preferred for quantitative angiographic studies on epicardial coronary vasomotility. When using ionic contrast agents, injection intervals of at least 3 min are required.

  17. Gd-HOPO Based High Relaxivity MRI Contrast Agents

    SciTech Connect

    Datta, Ankona; Raymond, Kenneth

    2008-11-06

    Tris-bidentate HOPO-based ligands developed in our laboratory were designed to complement the coordination preferences of Gd{sup 3+}, especially its oxophilicity. The HOPO ligands provide a hexadentate coordination environment for Gd{sup 3+} in which all he donor atoms are oxygen. Because Gd{sup 3+} favors eight or nine coordination, this design provides two to three open sites for inner-sphere water molecules. These water molecules rapidly exchange with bulk solution, hence affecting the relaxation rates of bulk water olecules. The parameters affecting the efficiency of these contrast agents have been tuned to improve contrast while still maintaining a high thermodynamic stability for Gd{sup 3+} binding. The Gd- HOPO-based contrast agents surpass current commercially available agents ecause of a higher number of inner-sphere water molecules, rapid exchange of inner-sphere water molecules via an associative mechanism, and a long electronic relaxation time. The contrast enhancement provided by these agents is at least twice that of commercial contrast gents, which are based on polyaminocarboxylate ligands.

  18. Microfabricated High-Moment Micrometer-sized MRI Contrast Agents

    PubMed Central

    Zabow, Gary; Dodd, Stephen J.; Shapiro, Erik; Moreland, John; Koretsky, Alan P.

    2010-01-01

    While chemically synthesized superparamagnetic microparticles have enabled much new research based on MRI-tracking of magnetically labeled cells, signal-to-noise levels still limit the potential range of applications. Here it is shown how, through top-down microfabrication, contrast agent relaxivity can be increased several-fold, which should extend the sensitivity of such cell tracking studies. Microfabricated agents can benefit from both higher magnetic moments and higher uniformity than their chemically synthesized counterparts, implying increased label visibility and more quantitative image analyses. To assess the performance of microfabricated micrometer-sized contrast agent particles, analytic models and numerical simulations are developed and tested against new microfabricated agents described in this paper, as well as against results of previous imaging studies of traditional chemically synthesized microparticle agents. Experimental data showing signal effects of 500-nanometer thick, 2-micrometer diameter, gold-coated iron and gold-coated nickel disks verify the simulations. Additionally, it is suggested that measures of location better than the pixel resolution can be obtained and that these are aided using well-defined contrast agent particles achievable through microfabrication techniques. PMID:20928829

  19. Revisiting an old friend: manganese-based MRI contrast agents

    PubMed Central

    Pan, Dipanjan; Caruthers, Shelton D.; Senpan, Angana; Schmieder, Ann H.; Wickline, Samuel A.; Lanza, Gregory M.

    2011-01-01

    Non-invasive cellular and molecular imaging techniques are emerging as a multidisciplinary field that offers promise in understanding the components, processes, dynamics and therapies of disease at a molecular level. Magnetic resonance imaging (MRI) is an attractive technique due to the absence of radiation and high spatial resolution which makes it advantageous over techniques involving radioisotopes. Typically paramagnetic and superparamagnetic metals are used as contrast materials for MR based techniques. Gadolinium has been the predominant paramagnetic contrast metal until the discovery and association of the metal with nephrogenic systemic fibrosis (NSF) in some patients with severe renal or kidney disease. Manganese was one of the earliest reported examples of paramagnetic contrast material for MRI because of its efficient positive contrast enhancement. In this review manganese based contrast agent approaches will be presented with a particular emphasis on nanoparticulate agents. We have discussed both classically used small molecule based blood pool contrast agents and recently developed innovative nanoparticle-based strategies highlighting a number of successful molecular imaging examples. PMID:20860051

  20. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration

    PubMed Central

    Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

    2016-01-01

    Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

  1. Sonophoresis Using Ultrasound Contrast Agents: Dependence on Concentration.

    PubMed

    Park, Donghee; Song, Gillsoo; Jo, Yongjun; Won, Jongho; Son, Taeyoon; Cha, Ohrum; Kim, Jinho; Jung, Byungjo; Park, Hyunjin; Kim, Chul-Woo; Seo, Jongbum

    2016-01-01

    Sonophoresis can increase skin permeability to various drugs in transdermal drug delivery. Cavitation is recognized as the predominant mechanism of sonophoresis. Recently, a new logical approach to enhance the efficiency of transdermal drug delivery was tried. It is to utilize the engineered microbubble and its resonant frequency for increase of cavitation activity. Actively-induced cavitation with low-intensity ultrasound (less than ~1 MPa) causes disordering of the lipid bilayers and the formation of aqueous channels by stable cavitation which indicates a continuous oscillation of bubbles. Furthermore, the mutual interactions of microbubble determined by concentration of added bubble are also thought to be an important factor for activity of stable cavitation, even in different characteristics of drug. In the present study, we addressed the dependence of ultrasound contrast agent concentration using two types of drug on the efficiency of transdermal drug delivery. Two types of experiment were designed to quantitatively evaluate the efficiency of transdermal drug delivery according to ultrasound contrast agent concentration. First, an experiment of optical clearing using a tissue optical clearing agent was designed to assess the efficiency of sonophoresis with ultrasound contrast agents. Second, a Franz diffusion cell with ferulic acid was used to quantitatively determine the amount of drug delivered to the skin sample by sonophoresis with ultrasound contrast agents. The maximum enhancement ratio of sonophoresis with a concentration of 1:1,000 was approximately 3.1 times greater than that in the ultrasound group without ultrasound contrast agent and approximately 7.5 times greater than that in the control group. These results support our hypothesis that sonophoresis becomes more effective in transdermal drug delivery due to the presence of engineered bubbles, and that the efficiency of transdermal drug delivery using sonophoresis with microbubbles depends on the

  2. Tumor Characterization with Dynamic Contrast Enhanced Magnetic Resonance Imaging and Biodegradable Macromolecular Contrast Agents in Mice

    PubMed Central

    Wu, Xueming; Feng, Yi; Jeong, Eun-Kee; Emerson, Lyska; Lu, Zheng-Rong

    2009-01-01

    Purpose To investigate the efficacy of polydisulfide-based biodegradable macromolecular contrast agents of different degradability and molecular weight for tumor characterization based on angiogenesis using dynamic contrast enhanced MRI (DCE-MRI). Methods Biodegradable macromolecular MRI contrast agents, GDCC and GDCP, with molecular weight of 20 and 70 KDa were evaluated for tumor characterization. The DCE-MRI studies were performed in nude mice bearing MDA PCa 2b and PC-3 human prostate tumor xenografts. Tumor angiogenic kinetic parameters, endothelium transfer coefficient (Ktrans) and fractional tumor plasma volume (fPV), were calculated from the DCE-MRI data using a two-compartment model. Results There was no significant difference in the fPV values between two tumor models estimated with the same agent except for GDCC-70. The Ktrans values in both tumor models decreased with increasing molecular weight of the agents. GDCC-70 showed a higher Ktrans values than GDCP-70 due to high degradability of the former in both tumor models (p < 0.05). The Ktrans values of MDA PCa 2b tumors were significantly higher than those of PC-3 tumors estimated by Gd(DTPA-BMA), GDCC-20, GDCC-70, GDCP-70, and albumin-(Gd-DTPA) (p < 0.05). Conclusions The polydisulfide based biodegradable macromolecular MRI contrast agents are promising in tumor characterization with dynamic contrast enhanced MRI. PMID:19597972

  3. Molecular Imaging and Contrast Agent Database (MICAD): Evolution and Progress

    PubMed Central

    Chopra, Arvind; Shan, Liang; Eckelman, W. C.; Leung, Kam; Latterner, Martin; Bryant, Stephen H.; Menkens, Anne

    2011-01-01

    The purpose of writing this review is to showcase the Molecular Imaging and Contrast Agent Database (MICAD; www.micad.nlm.nih.gov) to students, researchers and clinical investigators interested in the different aspects of molecular imaging. This database provides freely accessible, current, online scientific information regarding molecular imaging (MI) probes and contrast agents (CA) used for positron emission tomography, single-photon emission computed tomography, magnetic resonance imaging, x-ray/computed tomography, optical imaging and ultrasound imaging. Detailed information on >1000 agents in MICAD is provided in a chapter format and can be accessed through PubMed. Lists containing >4250 unique MI probes and CAs published in peer-reviewed journals and agents approved by the United States Food and Drug Administration (FDA) as well as a CSV file summarizing all chapters in the database can be downloaded from the MICAD homepage. Users can search for agents in MICAD on the basis of imaging modality, source of signal/contrast, agent or target category, preclinical or clinical studies, and text words. Chapters in MICAD describe the chemical characteristics (structures linked to PubChem), the in vitro and in vivo activities and other relevant information regarding an imaging agent. All references in the chapters have links to PubMed. A Supplemental Information Section in each chapter is available to share unpublished information regarding an agent. A Guest Author Program is available to facilitate rapid expansion of the database. Members of the imaging community registered with MICAD periodically receive an e-mail announcement (eAnnouncement) that lists new chapters uploaded to the database. Users of MICAD are encouraged to provide feedback, comments or suggestions for further improvement of the database by writing to the editors at: micad@nlm.nih.gov PMID:21989943

  4. Surface Modified Gadolinium Phosphate Nanoparticles as MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Dumont, Matthieu F.; Baligand, Celine; Knowles, Elisabeth S.; Meisel, Mark W.; Walter, Glenn A.; Talham, Daniel R.

    2012-02-01

    Nanoparticles of GdPO4H2O were synthesized in a water/oil microemulsion using IGEPAL CO-520 as surfactant resulting in 50 nm to 100 nm particles that are dispersible and stable in water. Using surface modification chemistry previously established for zirconium phosphonate surfaces,ootnotetext J. Monot et al., J. Am. Chem. Soc. 130 (2008) 6243. the particles are directly modified with 5'-phosphate terminated oligonucleotides, and the specific interaction of the divalent phosphate with Gd^3+ sites at the surface is demonstrated. The ability of the modified nanoparticles to act as MRI contrast agents was determined by performing MR relaxivity measurements at 14 T. Solutions of nanopure water, Feridex and Omniscan (FDA cleared contrast agents) in 0.25% agarose were used for comparison and control purposes. MRI data confirm that GdPO4H2O nanoparticles have relaxivities (r1,r2) comparable to commercially available contrast agents.ootnotetext H. Hifumi et al., J. Am. Chem. Soc. 128 (2006) 15090. In addition, biofunctionalization of the surface of the nanoparticles does not prevent their function as MRI contrast agents.

  5. Cell-Permeable MR Contrast Agents with Increased Intracellular Retention

    PubMed Central

    Endres, Paul J.; MacRenaris, Keith W.; Vogt, Stefan; Meade, Thomas J.

    2009-01-01

    Magnetic resonance imaging (MRI) is a technique used in both clinical and experimental settings to produce high resolution images of opaque organisms without ionizing radiation. Currently, MR imaging is augmented by contrast agents and the vast majority these small molecule Gd(III) chelates are confined to the extracellular regions. As a result, contrast agents are confined to vascular regions reducing their ability to provide information about cell physiology or molecular pathology. We have shown that polypeptides of arginine have the capacity to transport Gd(III) contrast agents across cell membranes. However, this transport is not unidirectional and once inside the cell the arginine-modified contrast agents efflux rapidly, decreasing the intracellular Gd(III) concentration and corresponding MR image intensity. By exploiting the inherent disulfide reducing environment of cells, thiol compounds, Gd(III)-DOTA-SS-Arg8 and Gd(III)-DTPA-SS-Arg8, are cleaved from their cell penetrating peptide transduction domains upon cell internalization. This reaction prolongs the cell-associated lifetime of the chelated Gd(III) by cleaving it from the cell transduction domain. PMID:18803414

  6. Macromolecular and Dendrimer Based Magnetic Resonance Contrast Agents

    PubMed Central

    Bumb, Ambika; Brechbiel, Martin W.; Choyke, Peter

    2010-01-01

    Magnetic resonance imaging (MRI) is a powerful imaging modality that can provide an assessment of function or molecular expression in tandem with anatomic detail. Over the last 20–25 years, a number of gadolinium based MR contrast agents have been developed to enhance signal by altering proton relaxation properties. This review explores a range of these agents from small molecule chelates, such as Gd-DTPA and Gd-DOTA, to macromolecular structures composed of albumin, polylysine, polysaccharides (dextran, inulin, starch), poly(ethylene glycol), copolymers of cystamine and cystine with GD-DTPA, and various dendritic structures based on polyamidoamine and polylysine (Gadomers). The synthesis, structure, biodistribution and targeting of dendrimer-based MR contrast agents are also discussed. PMID:20590365

  7. Paramagnetic self-assembled nanoparticles as supramolecular MRI contrast agents.

    PubMed

    Besenius, Pol; Heynens, Joeri L M; Straathof, Roel; Nieuwenhuizen, Marko M L; Bomans, Paul H H; Terreno, Enzo; Aime, Silvio; Strijkers, Gustav J; Nicolay, Klaas; Meijer, E W

    2012-01-01

    Nanometer-sized materials offer a wide range of applications in biomedical technologies, particularly imaging and diagnostics. Current scaffolds in the nanometer range predominantly make use of inorganic particles, organic polymers or natural peptide-based macromolecules. In contrast we hereby report a supramolecular approach for the preparation of self-assembled dendritic-like nanoparticles for applications as MRI contrast agents. This strategy combines the benefits from low molecular weight imaging agents with the ones of high molecular weight. Their in vitro properties are confirmed by in vivo measurements: post injection of well-defined and meta-stable nanoparticles allows for high-resolution blood-pool imaging, even at very low Gd(III) doses. These dynamic and modular imaging agents are an important addition to the young field of supramolecular medicine using well-defined nanometer-sized assemblies. PMID:22539406

  8. Novel design of multimodal MRI/NIR optical contrast agent

    NASA Astrophysics Data System (ADS)

    Guo, Kevin; Lin, Franck; Akers, Walter; Zheng, Jie; Teng, Bao; Vasalatiy, Olga; Griffiths, Gary L.; Gandjbakhche, Amir; Berezin, Mikhail Y.; Achilefu, Samuel

    2011-03-01

    We present a novel, dual modality gadolinium based MRI/near-infrared optical probe. Utilizing a fluorescent dye as a scaffold with attached Gd-chelating moiety, we demonstrated a substantial shortening of T1 relaxation time of water protons in vitro. The probe was compared to the commonly used MRI Gd-based contrast agents Magnevist® and Multihance® and showed superior contrast properties. The enhancement was due to strong albumin binding of the hydrophobic fluorophore and overall rigidification of the contrast agent. Due to the near-infrared optical properties of the probe and excellent MRI activity the proposed construct can be potentially utilized as a dual probe in multimodal MRI/NIR optical imaging.

  9. Extracardiac applications of MR blood pool contrast agent in children.

    PubMed

    Farmakis, Shannon G; Khanna, Geetika

    2014-12-01

    Magnetic resonance (MR) angiography has significantly reduced the need for diagnostic conventional angiography and is preferred over CT angiography in children because of its lack of ionizing radiation. The availability of gadofosveset trisodium (the only clinically approved blood pool MR contrast agent) has led to an increase in applications of MR for vascular imaging and an improvement in diagnostic quality of MR angiography. Gadofosveset is a gadolinium-based contrast agent that binds reversibly to albumin, resulting in increased paramagnetic effect and longer intravascular residence. This allows for high-resolution arterial and venous MR angiography, assessment of flow characteristics of vascular malformations, dynamic vascular imaging, and multi-station imaging with a single low-dose gadolinium contrast injection. The purpose of this pictorial essay is to facilitate understanding of the kinetics and safety profile of gadofosveset trisodium, discuss technical aspects of imaging, and illustrate advantages and extracardiac applications in pediatric body imaging. PMID:25408135

  10. Ultrasound Imaging Beyond the Vasculature with New Generation Contrast Agents

    PubMed Central

    Perera, Reshani H.; Hernandez, Christopher; Zhou, Haoyan; Kota, Pavan; Burke, Alan

    2015-01-01

    Current commercially available ultrasound contrast agents are gas-filled, lipid- or protein-stabilized microbubbles larger than 1 μm in diameter. Because the signal generated by these agents is highly dependent on their size, small yet highly echogenic particles have been historically difficult to produce. This has limited the molecular imaging applications of ultrasound to the blood pool. In the area of cancer imaging, microbubble applications have been constrained to imaging molecular signatures of tumor vasculature and drug delivery enabled by ultrasound-modulated bubble destruction. Recently, with the rise of sophisticated advancements in nanomedicine, ultrasound contrast agents, which are an order of magnitude smaller (100-500 nm) than their currently utilized counterparts, have been undergoing rapid development. These agents are poised to greatly expand the capabilities of ultrasound in the field of targeted cancer detection and therapy by taking advantage of the enhanced permeability and retention phenomenon of many tumors and can extravasate beyond the leaky tumor vasculature. Agent extravasation facilitates highly sensitive detection of cell surface or microenvironment biomarkers, which could advance early cancer detection. Likewise, when combined with appropriate therapeutic agents and ultrasound-mediated deployment on demand, directly at the tumor site, these nanoparticles have been shown to contribute to improved therapeutic outcomes. Ultrasound's safety profile, broad accessibility and relatively low cost make it an ideal modality for the changing face of healthcare today. Aided by the multifaceted nano-sized contrast agents and targeted theranostic moieties described herein, ultrasound can considerably broaden its reach in future applications focused on the diagnosis and staging of cancer. PMID:25580914

  11. Interactive neonatal gastrointestinal magnetic resonance imaging using fruit juice as an oral contrast media

    PubMed Central

    2014-01-01

    Background The objective was to evaluate the use of fruit juice with an interactive inversion recovery (IR) MR pulse sequence to visualise the gastrointestinal tract. Methods We investigated the relaxation properties of 12 different natural fruit juices in vitro, to identify which could be used as oral contrast. We then describe our initial experience using an interactive MR pulse sequence to allow optimal visualisation after administering pineapple juice orally, and suppressing pre-existing bowel fluid contents, with variable TI in three adult and one child volunteer. Results Pineapple juice (PJ) had both the shortest T1 (243 ms) and shortest T2 (48 ms) of the fruit juices tested. Optimal signal differentiation between pre-existing bowel contents and oral PJ administration was obtained with TIs of between 900 and 1100 ms. Conclusion The use of an inversion recovery preparation allowed long T1 pre-existing bowel contents to be suppressed whilst the short T1 of fruit juice acts as a positive contrast medium. Pineapple juice could be used as oral contrast agent for neonatal gastrointestinal magnetic resonance imaging. PMID:25245815

  12. Redox- and Hypoxia-Responsive MRI Contrast Agents

    PubMed Central

    Do, Quyen N.; Ratnakar, James S.; Kovács, Zoltán

    2014-01-01

    The development of responsive or “smart” magnetic resonance imaging (MRI) contrast agents that can report specific biomarker or biological events has been the focus of MRI contrast agent research over the past 20 years. Among various biological hallmarks of interest, tissue redox and hypoxia are particularly important owing to their roles in disease states and metabolic consequences. Herein we review the development of redox-/hypoxia-sensitive T1 shortening and paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents. Traditionally, the relaxivity of redox-sensitive Gd3+-based complexes is modulated through changes in the ligand structure or molecular rotation, while PARACEST sensors exploit the sensitivity of the metal-bound water exchange rate to electronic effects of the ligand-pendant arms and alterations in the coordination geometry. Newer designs involve complexes of redox-active metal ions in which the oxidation states have different magnetic properties. The challenges of translating redox- and hypoxia-sensitive agents in vivo are also addressed. PMID:24825674

  13. Redox- and hypoxia-responsive MRI contrast agents.

    PubMed

    Do, Quyen N; Ratnakar, James S; Kovács, Zoltán; Sherry, A Dean

    2014-06-01

    The development of responsive or "smart" magnetic resonance imaging (MRI) contrast agents that can report specific biomarker or biological events has been the focus of MRI contrast agent research over the past 20 years. Among various biological hallmarks of interest, tissue redox and hypoxia are particularly important owing to their roles in disease states and metabolic consequences. Herein we review the development of redox-/hypoxia-sensitive T1 shortening and paramagnetic chemical exchange saturation transfer (PARACEST) MRI contrast agents. Traditionally, the relaxivity of redox-sensitive Gd(3+) -based complexes is modulated through changes in the ligand structure or molecular rotation, while PARACEST sensors exploit the sensitivity of the metal-bound water exchange rate to electronic effects of the ligand-pendant arms and alterations in the coordination geometry. Newer designs involve complexes of redox-active metal ions in which the oxidation states have different magnetic properties. The challenges of translating redox- and hypoxia-sensitive agents in vivo are also addressed. PMID:24825674

  14. Effects of ultrasound and ultrasound contrast agent on vascular tissue

    PubMed Central

    2012-01-01

    Background Ultrasound (US) imaging can be enhanced using gas-filled microbubble contrast agents. Strong echo signals are induced at the tissue-gas interface following microbubble collapse. Applications include assessment of ventricular function and virtual histology. Aim While ultrasound and US contrast agents are widely used, their impact on the physiological response of vascular tissue to vasoactive agents has not been investigated in detail. Methods and results In the present study, rat dorsal aortas were treated with US via a clinical imaging transducer in the presence or absence of the US contrast agent, Optison. Aortas treated with both US and Optison were unable to contract in response to phenylephrine or to relax in the presence of acetylcholine. Histology of the arteries was unremarkable. When the treated aortas were stained for endothelial markers, a distinct loss of endothelium was observed. Importantly, terminal deoxynucleotidyl transferase mediated dUTP nick-end-labeling (TUNEL) staining of treated aortas demonstrated incipient apoptosis in the endothelium. Conclusions Taken together, these ex vivo results suggest that the combination of US and Optison may alter arterial integrity and promote vascular injury; however, the in vivo interaction of Optison and ultrasound remains an open question. PMID:22805356

  15. Biodegradable Polydisulfide Dendrimer Nanoclusters as MRI Contrast Agents

    PubMed Central

    Huang, Ching-Hui; Nwe, Kido; Zaki, Ajlan Al; Brechbiel, Martin W.; Tsourkas, Andrew

    2012-01-01

    Gd-conjugated dendrimer nanoclusters (DNCs) are a promising platform for the early detection of disease; however, their clinical utility is potentially limited due to safety concerns related to nephrogenic systemic fibrosis (NSF). In this paper, biodegradable DNCs were prepared with polydisulfide linkages between the individual dendrimers to facilitate excretion. Further, DNCs were labeled with pre-metalated Gd chelates to eliminate the risk of free Gd becoming entrapped in dendrimer cavities. The biodegradable polydisulfide DNCs possessed a circulation half-life of > 1.6 h in mice and produced significant contrast enhancement in the abdominal aorta and kidneys for as long as 4 h. The DNCs were reduced in circulation as a result of thiol-disulfide exchange and the degradation products were rapidly excreted via renal filtration. These agents demonstrated effective and prolonged in vivo contrast enhancement and yet minimized Gd tissue retention. Biodegradable polydisulfide DNCs represent a promising biodegradable macromolecular MRI contrast agent for magnetic resonance angiography and can potentially be further developed into target specific MRI contrast agents. PMID:23098069

  16. Dual-frequency transducer for nonlinear contrast agent imaging.

    PubMed

    Guiroy, Axel; Novell, Anthony; Ringgaard, Erling; Lou-Moeller, Rasmus; Grégoire, Jean-Marc; Abellard, André-Pierre; Zawada, Tomasz; Bouakaz, Ayache; Levassort, Franck

    2013-12-01

    Detection of high-order nonlinear components issued from microbubbles has emerged as a sensitive method for contrast agent imaging. Nevertheless, the detection of these high-frequency components, including the third, fourth, and fifth harmonics, remains challenging because of the lack of transducer sensitivity and bandwidth. In this context, we propose a new design of imaging transducer based on a simple fabrication process for high-frequency nonlinear imaging. The transducer is composed of two elements: the outer low-frequency (LF) element was centered at 4 MHz and used in transmit mode, whereas the inner high-frequency (HF) element centered at 14 MHz was used in receive mode. The center element was pad-printed using a lead zirconate titanate (PZT) paste. The outer element was molded using a commercial PZT, and curved porous unpoled PZT was used as backing. Each piezoelectric element was characterized to determine the electromechanical performance with thickness coupling factor around 45%. After the assembly of the two transducer elements, hydrophone measurements (electroacoustic responses and radiation patterns) were carried out and demonstrated a large bandwidth (70% at -3 dB) of the HF transducer. Finally, the transducer was evaluated for contrast agent imaging using contrast agent microbubbles. The results showed that harmonic components (up to the sixth harmonic) of the microbubbles were successfully detected. Moreover, images from a flow phantom were acquired and demonstrated the potential of the transducer for high-frequency nonlinear contrast imaging. PMID:24297028

  17. Molecular nanomagnets as contrast agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Rodríguez, Elisenda; Roig, Anna; Molins, Elies; Arús, Carles; Cabañas, Miquel; Quintero, María Rosa; Cerdán, Sebastián; Sanfeliu, Coral

    2003-03-01

    Magnetic resonance imaging (MRI) is a non-invasive technique used in medicine to produce high quality images of human body slices. In order to enhance the contrast between different organs or to reveal altered portions of them such necrosis or tumors, the administration of a contrast agent is highly convenient. Currently Gd-DTPA, a paramagnetic complex, is the most widely administered compound. In this context, we have assayed molecular nanomagnets as MRI contrast agents. The complex [(tacn)_6Fe_8(μ_3-O)_2(μ_2-OH)_12]Br_8·9H_2O^1(Fe8 in brief) has been evaluated and shorter relaxation times, T1 and T_2, have been obtained for Fe8 than those obtained for the commercial Gd-DTPA. No toxic effects have been observed at concentrations up to 1 mM of Fe8 in cultured cells. Phantom studies with T_1-weighted MRI at 9.4 Tesla suggest that Fe8 can have potentiality as T_1-contrast agent. ^1Wieghardt K Angew Chem Intl Ed Engl 23 1 (1984) 77

  18. Cardiac arrhythmias produced by ultrasound and contrast agents

    NASA Astrophysics Data System (ADS)

    Rota, Claudio

    Ultrasound is used widely in medicine for both diagnostic and therapeutic applications. Ultrasound contrast agents are suspensions of gas-filled microbubbles used to enhance diagnostic imaging. Microbubble contrast agents can increase the likelihood of bioeffects of ultrasound associated with acoustic cavitation. Under certain exposure conditions, the interaction of ultrasound with cardiac tissues can produce cardiac arrhythmias. The general objective of this thesis was to develop a greater understanding of ultrasound-induced premature cardiac beats. The hypothesis guiding this work was that acoustic cavitation is the physical mechanism for the production of arrhythmias with ultrasound. This hypothesis was tested through a series of experiments with mice in vivo and theoretical investigations. Results of this research supported the acoustic cavitation hypothesis. The acoustic pressure threshold for premature beats was significantly lower with microbubble contrast agents present in the blood than without. With microbubbles, the threshold for premature beats was below the current output limits of diagnostic devices. The threshold was not significantly dependent upon contrast agent type and was not influenced by contrast agent dose over three orders of magnitude. Furthermore, the dependence of the threshold on acoustic frequency was consistent with the frequency dependence of acoustic cavitation. Experimentally determined thresholds for premature beats in vivo were in excellent agreement with theoretically estimated thresholds for inertial cavitation. A passive cavitation detector (PCD) was used to measure the acoustic emissions produced by cavitating microbubbles in vivo. A direct correlation between the amplitude of the PCD and the percentage of ultrasound pulses producing a premature beat was consistent with cavitation as a mechanism for this bioeffect. Although this thesis focused on the mechanistic understanding of ultrasound-induced arrhythmias, more persistent

  19. Screening CEST contrast agents using ultrafast CEST imaging

    NASA Astrophysics Data System (ADS)

    Xu, Xiang; Yadav, Nirbhay N.; Song, Xiaolei; McMahon, Michael T.; Jerschow, Alexej; van Zijl, Peter C. M.; Xu, Jiadi

    2016-04-01

    A chemical exchange saturation transfer (CEST) experiment can be performed in an ultrafast fashion if a gradient field is applied simultaneously with the saturation pulse. This approach has been demonstrated for studying dia- and para-magnetic CEST agents, hyperpolarized Xe gas and in vivo spectroscopy. In this study we present a simple method for the simultaneous screening of multiple samples. Furthermore, by interleaving a number of saturation and readout periods within the TR, a series of images with different saturation times can be acquired, allowing for the quantification of exchange rates using the variable saturation time (QUEST) approach in a much accelerated fashion, thus enabling high throughput screening of CEST contrast agents.

  20. Nanoshells as an optical coherence tomography contrast agent

    NASA Astrophysics Data System (ADS)

    Barton, Jennifer K.; Halas, Naomi J.; West, Jennifer L.; Drezek, Rebekah A.

    2004-07-01

    Nanoshells are a layered dielectric core/metal shell composite nanostructure with an optical resonance geometrically tunable through the visible and near infrared. Due to their small size, ability to generate a strong backscattering signal, and potential for surface modification, they may be an ideal in vivo optical coherence tomography contrast agent. We performed a pilot study to assess their capabilities. Images of a cuvette filled with dilute nanoshells, 2 μm polystyrene microspheres, or a combination were obtained. When compared to microspheres, images of the nanoshells where much brighter and attenuation of the bottom cuvette interface less. Injection of micropheres into the tail vein of mice and hamsters caused a noticeable brightening of OCT images of the dorsal skin. These pilot studies indicate that nanoshells may be an excellent OCT contrast agent; work is continuing to determine optimum nanoshell parameters and applications.

  1. Tunable Diacetylene Polymerized Shell Microbubbles as Ultrasound Contrast Agents

    PubMed Central

    Park, Yoonjee; Luce, Adam C.; Whitaker, Ragnhild D.; Amin, Bhumica; Cabodi, Mario; Nap, Rikkert J.; Szleifer, Igal; Cleveland, Robin O.; Nagy, Jon O.; Wong, Joyce Y.

    2012-01-01

    Monodisperse gas microbubbles, encapsulated with a shell of photopolymerizable diacetylene lipids and phospholipids, were produced by microfluidic flow focusing, for use as ultrasound contrast agents. The stability of the polymerized shell microbubbles against both aggregation and gas dissolution under physiological conditions was studied. Polyethylene glycol (PEG) 5000, which was attached to the diacetylene lipids, was predicted by molecular theory to provide more steric hindrance against aggregation than PEG 2000 and this was confirmed experimentally. The polymerized shell microbubbles were found to have higher shell-resistance than nonpolymerizable shell microbubbles and commercially available microbubbles (Vevo MicroMarker). The acoustic stability under 7.5 MHz ultrasound insonation was significantly greater than for the two comparison microbubbles. The acoustic stability was tunable by varying the amount of diacetylene lipid. Thus, our polymerized shell microbubbles are a promising platform for ultrasound contrast agents. PMID:22260537

  2. Towards MRI T2 contrast agents of increased efficiency

    NASA Astrophysics Data System (ADS)

    Branca, Marlène; Marciello, Marzia; Ciuculescu-Pradines, Diana; Respaud, Marc; Morales, Maria del Puerto; Serra, Raphael; Casanove, Marie-José; Amiens, Catherine

    2015-03-01

    Magnetic nanoparticles can be efficient contrast agents for T2 weighted magnetic resonance imaging (MRI) after tuning of some key parameters such as size, surface state, colloidal stability and magnetization, thus motivating the development of new synthetic pathways. In this paper we report the effects of surface coating on the efficiency of two different types of iron based nanoparticles (NPs) as MRI contrast agents. Starting from well-defined hydrophobic iron oxide nanospheres and iron nanocubes of 13 nm size, we have used three methods to increase their hydrophilicity and transfer them into water: surface ligand modification, ligand exchange or encapsulation. The NPs obtained have been characterized by dynamic light scattering and transmission electron microscopy, and the relaxivities of their stable colloidal solutions in water have been determined. Among all samples prepared, iron nanocubes coated by silica display the highest relaxivity (r2) value: 628 s-1 mM-1.

  3. Odontonutraceuticals: Pleiotropic Phytotherapeutic Agents for Oral Health

    PubMed Central

    Varoni, Elena Maria; Iriti, Marcello

    2016-01-01

    This brief commentary aims to focus on the urgency of further clinical research on phytotherapy in dentistry, and, noteworthy, to propose, for the first time, to the best of our knowledge, the term “odontonutraceuticals” to identify those phytochemicals relevant for the prevention and the treatment of oral diseases. A valuable impact is expected on nutritional, dental and biomedical sciences, suggesting the use of the suffix "odonto-" to define a specific field of nutraceutical research. PMID:26927132

  4. The in vivo relaxivity of MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Shuter, Borys

    1999-11-01

    Post-contrast clinical 1H Magnetic Resonance Images have to date been interpreted with little regard for possible variations in the in-vivo properties of injected magnetic pharmaceuticals (contrast agents), particularly in their relaxivity or ability to alter tissue relaxation rates, T2-1 and T 2-1, per unit concentration. The relaxivities of contrast agents have only rarely been measured in-vivo, measurements usually being performed on excised tissues and at magnetic field strengths lower than used in clinical practice. Some researchers have simply assumed that relaxivities determined in homogeneous tissue phantoms were applicable in-vivo. In this thesis, the relaxivities of two contrast agents, Gd-DTPA and Gd-EOB-DTPA, were measured in simple tissue phantoms and in the kidney and liver of intact, but sacrificed, Wistar rats using a clinical MR scanner with a magnetic field of 1.5 Tesla. T1 and T2 were determined from sets of images acquired using a standard clinical spin-echo pulse sequence. The contrast agent concentration in tissue was assessed by radioassay of 153Gd-DTPA or 153Gd-EOB-DTPA, mixed with the normal compound prior to injection. Relaxivity was taken as the slope of a linear regression fit of relaxation rate against Gd concentration. The relaxivities of Gd-EOB-DTPA were similarly determined in normal and biliary- obstructed guinea pigs. Relaxivities in tissue differed significantly from values obtained in simple phantoms. Kidney T1 relaxivity was reduced for both compounds in normal animals. Three days or more of biliary obstruction produced further reductions in kidney T1 relaxivity of Gd-EOB-DTPA, providing strong evidence that disease affects contrast agent relaxivity. Kidney T2 relaxivity was much greater than T1 relaxivity and was also depressed by biliary obstruction. Liver T1 and T 2 relaxivites were increased above phantom values, but were not affected by the biliary obstruction. Water compartmentalisation, macromolecular binding, proton

  5. The effective use of acai juice, blueberry juice and pineapple juice as negative contrast agents for magnetic resonance cholangiopancreatography in children.

    PubMed

    Bittman, Mark E; Callahan, Michael J

    2014-07-01

    Magnetic resonance cholangiopancreatography (MRCP) is commonly performed in the evaluation of known or suspected pancreaticobiliary disease in children. The administration of a negative oral contrast agent can improve the quality of the examination without significant additional cost. We describe our experience with certain brands of acai juice, blueberry juice and pineapple juice as negative oral contrast agents in children. We believe these fruit juices are safe, palatable and may improve MRCP image quality. PMID:24573534

  6. Beat frequency ultrasonic microsphere contrast agent detection system

    NASA Technical Reports Server (NTRS)

    Pretlow, III, Robert A. (Inventor); Yost, William T. (Inventor); Cantrell, Jr., John H. (Inventor)

    1997-01-01

    A system for and method of detecting and measuring concentrations of an ultrasonically-reflective microsphere contrast agent involving detecting non-linear sum and difference beat frequencies produced by the microspheres when two impinging signals with non-identical frequencies are combined by mixing. These beat frequencies can be used for a variety of applications such as detecting the presence of and measuring the flow rates of biological fluids and industrial liquids, including determining the concentration level of microspheres in the myocardium.

  7. Acoustic properties of organic powders as ultrasonic contrast agents

    NASA Astrophysics Data System (ADS)

    Burov, V. A.; Loginov, S. V.; Dmitriev, K. V.

    2011-11-01

    The results of experiments on measuring attenuation and the effective acoustic nonlinear parameter of the second order are given for a suspension of cocoa-powder in water at different concentrations of the suspension. In the process of evaluating the value of the nonlinear parameter the attenuation in the suspension and generation of the second harmonic not only in the suspension but also in water are taken into account. The obtained results are evidence of the possibility of using a suspension of cocoa-powder in water as a technical substitute for ultrasonic contrast agents. The values of attenuation (up to 60 m-1 at the concentration of 1 g of the powder per 1 l of water) and the nonlinear parameter (up to 120 m-1 at the same concentration) mean that the suspension of cocoa-powder in water has smaller attenuation and the nonlinear parameter than ultrasonic contrast agents at the same concentration. However, these values for the suspension differ considerably from corresponding values for water or blood and, therefore, a suspension of cocoa-powder in water is a promising "substitute" for ultrasonic contrast agents in the case of technical testing of systems for nonlinear tomography of a blood flow, but cannot replace them in medical studies.

  8. Target-specific contrast agents for magnetic resonance microscopy

    PubMed Central

    Blackwell, Megan L.; Farrar, Christian T.; Fischl, Bruce; Rosen, Bruce R.

    2009-01-01

    High-resolution ex vivo magnetic resonance (MR) imaging can be used to delineate prominent architectonic features in the human brain, but increased contrast is required to visualize more subtle distinctions. To aid MR sensitivity to cell density and myelination, we have begun the development of target-specific paramagnetic contrast agents. This work details the first application of luxol fast blue (LFB), an optical stain for myelin, as a white matter-selective MR contrast agent for human ex vivo brain tissue. Formalin-fixed human visual cortex was imaged with an isotropic resolution between 80 and 150 μm at 4.7 and 14 T before and after en bloc staining with LFB. Longitudinal (R1) and transverse (R2) relaxation rates in LFB-stained tissue increased proportionally with myelination at both field strengths. Changes in R1 resulted in larger contrast-to-noise ratios (CNR), per unit time, on T1-weighted images between more myelinated cortical layers (IV–VI) and adjacent, superficial layers (I–III) at both field strengths. Specifically, CNR for LFB-treated samples increased by 229±13% at 4.7 T and 269±25% at 14 T when compared to controls. Also, additional cortical layers (IVca, IVd, and Va) were resolvable in 14T-MR images of LFB-treated samples but not in control samples. After imaging, samples were sliced in 40-micron sections, mounted, and photographed. Both the macroscopic and microscopic distributions of LFB were found to mimic those of traditional histological preparations. Our results suggest target-specific contrast agents will enable more detailed MR images with applications in imaging pathological ex vivo samples and constructing better MR atlases from ex vivo brains. PMID:19385012

  9. Hepatobiliary MR Imaging with Gadolinium Based Contrast Agents

    PubMed Central

    Frydrychowicz, Alex; Lubner, Meghan G.; Brown, Jeffrey J.; Merkle, Elmar M.; Nagle, Scott K.; Rofsky, Neil M.; Reeder, Scott B.

    2011-01-01

    The advent of gadolinium-based “hepatobiliary” contrast agents offers new opportunities for diagnostic MRI and has triggered a great interest for innovative imaging approaches to the liver and bile ducts. In this review article we will discuss the imaging properties of the two gadolinium-based hepatobiliary contrast agents currently available in the USA, gadobenate dimeglumine and gadoxetic acid, as well as important pharmacokinetic differences that affect their diagnostic performance. We will review potential applications, protocol optimization strategies, as well as diagnostic pitfalls. A variety of illustrative case examples will be used to demonstrate the role of these agents in detection and characterization of liver lesions as well as for imaging the biliary system. Changes in MR protocols geared towards optimizing workflow and imaging quality will also be discussed. It is our aim that the information provided in this article will facilitate the optimal utilization of these agents, and will stimulate the reader‘s pursuit of new applications for future benefit. PMID:22334493

  10. The Paramagnetic Pillared Bentonites as Digestive Tract MRI Contrast Agents

    NASA Astrophysics Data System (ADS)

    Mojović, Miloš; Daković, Marko; Omerašević, Mia; Mojović, Zorica; Banković, Predrag; Milutinović-Nikolić, Aleksandra; Jovanović, Dušan

    The increased use of imaging techniques in diagnostic studies, such as MRI, has contributed to the development of the wide range of new materials which could be successfully used as image improving agents. However, there is a lack of such substances in the area of gastrointestinal tract MRI. Many of the traditionally popular relaxation altering agents show poor results and disadvantages provoking black bowel, side effects of diarrhea and the presence of artifacts arising from clumping. Paramagnetic species seem to be potentially suitable agents for these studies, but contrast opacification has been reported and less than 60% of the gastrointestinal tract magnetic resonance scans showed improved delineation of abdominal pathologies. The new solution has been proposed as zeolites or smectite clays (hectorite and montmorillonite) enclosing of paramagnetic metal ions obtained by ion-exchange methods. However, such materials have problems of leakage of paramagnetic ions causing the appearance of the various side-effects. In this study we show that Co+2 and Dy+3 paramagnetic-pillared bentonites could be successfully used as MRI digestive tract non-leaching contrast agents, altering the longitudinal and transverse relaxation times of fluids in contact with the clay minerals.

  11. Biocompatible Nanocomplexes for Molecular Targeted MRI Contrast Agent

    NASA Astrophysics Data System (ADS)

    Chen, Zhijin; Yu, Dexin; Wang, Shaojie; Zhang, Na; Ma, Chunhong; Lu, Zaijun

    2009-07-01

    Accurate diagnosis in early stage is vital for the treatment of Hepatocellular carcinoma. The aim of this study was to investigate the potential of poly lactic acid-polyethylene glycol/gadolinium-diethylenetriamine-pentaacetic acid (PLA-PEG/Gd-DTPA) nanocomplexes using as biocompatible molecular magnetic resonance imaging (MRI) contrast agent. The PLA-PEG/Gd-DTPA nanocomplexes were obtained using self-assembly nanotechnology by incubation of PLA-PEG nanoparticles and the commercial contrast agent, Gd-DTPA. The physicochemical properties of nanocomplexes were measured by atomic force microscopy and photon correlation spectroscopy. The T1-weighted MR images of the nanocomplexes were obtained in a 3.0 T clinical MR imager. The stability study was carried out in human plasma and the distribution in vivo was investigated in rats. The mean size of the PLA-PEG/Gd-DTPA nanocomplexes was 187.9 ± 2.30 nm, and the polydispersity index was 0.108, and the zeta potential was -12.36 ± 3.58 mV. The results of MRI test confirmed that the PLA-PEG/Gd-DTPA nanocomplexes possessed the ability of MRI, and the direct correlation between the MRI imaging intensities and the nano-complex concentrations was observed ( r = 0.987). The signal intensity was still stable within 2 h after incubation of the nanocomplexes in human plasma. The nanocomplexes gave much better image contrast effects and longer stagnation time than that of commercial contrast agent in rat liver. A dose of 0.04 mmol of gadolinium per kilogram of body weight was sufficient to increase the MRI imaging intensities in rat livers by five-fold compared with the commercial Gd-DTPA. PLA-PEG/Gd-DTPA nanocomplexes could be prepared easily with small particle sizes. The nanocomplexes had high plasma stability, better image contrast effect, and liver targeting property. These results indicated that the PLA-PEG/Gd-DTPA nanocomplexes might be potential as molecular targeted imaging contrast agent.

  12. Hexameric Mn(II) Dendrimer as MRI Contrast Agent

    PubMed Central

    Zhu, Jiang; Gale, Eric M.; Atanasova, Iliyana; Rietz, Tyson A.

    2014-01-01

    A Mn(II) chelating dendrimer was prepared as a contrast agent for MRI applications. The dendrimer comprises six tyrosine-derived [Mn(EDTA)(H2O)]2− moieties coupled to a cyclotriphosphazene core. Variable temperature 17O NMR revealed a single water co-ligand per Mn(II) that undergoes fast water exchange (kex = (3.0±0.1) × 108 s−1 at 37 °C). The 37 °C per Mn(II) relaxivity ranged from 8.2 to 3.8 mM−1s−1 from 0.47 to 11.7T, and is 6-fold higher on a per molecule basis. From this field dependence a rotational correlation time was estimated as 0.45±0.02 ns. The imaging and pharmacokinetic properties of the dendrimer were compared to clinically used [Gd(DTPA)(H2O)]2− in mice at 4.7T. On first pass, the higher per ion relaxivity of the dendrimer resulted in 2-fold greater blood signal than for [Gd(DTPA)(H2O)]2−. Blood clearance was fast and elimination occurred through both the renal and hepatobiliary routes. This Mn(II) containing dendrimer represents potential alternative to Gd-based contrast agents, especially in patients with chronic kidney disease where the use of current Gd-based agents may be contraindicated. PMID:25224391

  13. Multifunctional Photosensitizer-Based Contrast Agents for Photoacoustic Imaging

    PubMed Central

    Ho, Chris Jun Hui; Balasundaram, Ghayathri; Driessen, Wouter; McLaren, Ross; Wong, Chi Lok; Dinish, U. S.; Attia, Amalina Binte Ebrahim; Ntziachristos, Vasilis; Olivo, Malini

    2014-01-01

    Photoacoustic imaging is a novel hybrid imaging modality combining the high spatial resolution of optical imaging with the high penetration depth of ultrasound imaging. Here, for the first time, we evaluate the efficacy of various photosensitizers that are widely used as photodynamic therapeutic (PDT) agents as photoacoustic contrast agents. Photoacoustic imaging of photosensitizers exhibits advantages over fluorescence imaging, which is prone to photobleaching and autofluorescence interference. In this work, we examined the photoacoustic activity of 5 photosensitizers: zinc phthalocyanine, protoporphyrin IX, 2,4-bis [4-(N,N-dibenzylamino)-2,6-dihydroxyphenyl] squaraine, chlorin e6 and methylene blue in phantoms, among which zinc phthalocyanine showed the highest photoacoustic activity. Subsequently, we evaluated its tumor localization efficiency and biodistribution at multiple time points in a murine model using photoacoustic imaging. We observed that the probe localized at the tumor within 10 minutes post injection, reaching peak accumulation around 1 hour and was cleared within 24 hours, thus, demonstrating the potential of photosensitizers as photoacoustic imaging contrast agents in vivo. This means that the known advantages of photosensitizers such as preferential tumor uptake and PDT efficacy can be combined with photoacoustic imaging capabilities to achieve longitudinal monitoring of cancer progression and therapy in vivo. PMID:24938638

  14. What We Can Really Do with Bioresponsive MRI Contrast Agents.

    PubMed

    Angelovski, Goran

    2016-06-13

    Bioresponsive MRI contrast agents hold great promise for monitoring major physiological and pathological processes in a non-invasive manner. They are capable of altering the acquired MRI signal as a consequence of changes in their microenvironment, thus allowing real-time functional reporting in living organisms. Importantly, chemistry offers diverse solutions for the design of agents which respond to a great number of specific targets. However, the path to the successful utilization of these biomarkers in the desired functional MRI studies involves careful consideration of multiple scientific, technical, and practical issues across various research disciplines. This Minireview highlights the critical steps for planning and executing such multidisciplinary projects with an aim to substantially improve our knowledge of essential biological processes. PMID:27112329

  15. Screening CEST contrast agents using ultrafast CEST imaging.

    PubMed

    Xu, Xiang; Yadav, Nirbhay N; Song, Xiaolei; McMahon, Michael T; Jerschow, Alexej; van Zijl, Peter C M; Xu, Jiadi

    2016-04-01

    A chemical exchange saturation transfer (CEST) experiment can be performed in an ultrafast fashion if a gradient field is applied simultaneously with the saturation pulse. This approach has been demonstrated for studying dia- and para-magnetic CEST agents, hyperpolarized Xe gas and in vivo spectroscopy. In this study we present a simple method for the simultaneous screening of multiple samples. Furthermore, by interleaving a number of saturation and readout periods within the TR, a series of images with different saturation times can be acquired, allowing for the quantification of exchange rates using the variable saturation time (QUEST) approach in a much accelerated fashion, thus enabling high throughput screening of CEST contrast agents. PMID:26969814

  16. Gadolinium nanoparticles and contrast agent as radiation sensitizers.

    PubMed

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist(®) in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL(-1)), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly 'energy dependent' for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs. PMID:25988839

  17. Gadolinium nanoparticles and contrast agent as radiation sensitizers

    NASA Astrophysics Data System (ADS)

    Taupin, Florence; Flaender, Mélanie; Delorme, Rachel; Brochard, Thierry; Mayol, Jean-François; Arnaud, Josiane; Perriat, Pascal; Sancey, Lucie; Lux, François; Barth, Rolf F.; Carrière, Marie; Ravanat, Jean-Luc; Elleaume, Hélène

    2015-06-01

    The goal of the present study was to evaluate and compare the radiosensitizing properties of gadolinium nanoparticles (NPs) with the gadolinium contrast agent (GdCA) Magnevist® in order to better understand the mechanisms by which they act as radiation sensitizers. This was determined following either low energy synchrotron irradiation or high energy gamma irradiation of F98 rat glioma cells exposed to ultrasmall gadolinium NPs (GdNPs, hydrodynamic diameter of 3 nm) or GdCA. Clonogenic assays were used to quantify cell survival after irradiation in the presence of Gd using monochromatic x-rays with energies in the 25 keV-80 keV range from a synchrotron and 1.25 MeV gamma photons from a cobalt-60 source. Radiosensitization was demonstrated with both agents in combination with X-irradiation. At the same concentration (2.1 mg mL-1), GdNPS had a greater effect than GdCA. The maximum sensitization-enhancement ratio at 4 Gy (SER4Gy) was observed at an energy of 65 keV for both the nanoparticles and the contrast agent (2.44   ±   0.33 and 1.50   ±   0.20, for GdNPs and GdCA, respectively). At a higher energy (1.25 MeV), radiosensitization only was observed with GdNPs (1.66   ±   0.17 and 1.01   ±   0.11, for GdNPs and GdCA, respectively). The radiation dose enhancements were highly ‘energy dependent’ for both agents. Secondary-electron-emission generated after photoelectric events appeared to be the primary mechanism by which Gd contrast agents functioned as radiosensitizers. On the other hand, other biological mechanisms, such as alterations in the cell cycle may explain the enhanced radiosensitizing properties of GdNPs.

  18. [Current status of oral immunomodulatory and immunosuppressive agents].

    PubMed

    Meller, S; Baran, A M; Braun, S A; Klossowski, N; Homey, B

    2014-02-01

    Various dermatological disorders require treatments with immunosuppressive or immunomodulatory agents. Nevertheless, several studies demonstrate low prescription rates for systemic treatments. This low usage may be a result of physicians' low levels of confidence in administering systemic treatments. However, immunosuppressive treatments represent safe options when potential side effects as well as pharmacological interactions are considered. This review overviews the most important oral immunosuppressive or immunomodulatory agents and summarizes their mode of actions, indications, and adverse effects. Biologics that require intravenous or subcutaneous application are not included, but novel and new agents likely to be released soon are considered. PMID:24549480

  19. Modified Gadonanotubes as a promising novel MRI contrasting agent

    PubMed Central

    2013-01-01

    Background and purpose of the study Carbon nanotubes (CNTs) are emerging drug and imaging carrier systems which show significant versatility. One of the extraordinary characteristics of CNTs as Magnetic Resonance Imaging (MRI) contrasting agent is the extremely large proton relaxivities when loaded with gadolinium ion (Gdn3+) clusters. Methods In this study equated Gdn3+ clusters were loaded in the sidewall defects of oxidized multiwalled (MW) CNTs. The amount of loaded gadolinium ion into the MWCNTs was quantified by inductively coupled plasma (ICP) method. To improve water solubility and biocompatibility of the system, the complexes were functionalized using diamine-terminated oligomeric poly (ethylene glycol) via a thermal reaction method. Results Gdn3+ loaded PEGylated oxidized CNTs (Gdn3+@CNTs-PEG) is freely soluble in water and stable in phosphate buffer saline having particle size of about 200 nm. Transmission electron microscopy (TEM) images clearly showed formation of PEGylated CNTs. MRI analysis showed that the prepared solution represents 10% more signal intensity even in half concentration of Gd3+ in comparison with commerciality available contrasting agent Magnevist®. In addition hydrophilic layer of PEG at the surface of CNTs could prepare stealth nanoparticles to escape RES. Conclusion It was shown that Gdn3+@CNTs-PEG was capable to accumulate in tumors through enhanced permeability and retention effect. Moreover this system has a potential for early detection of diseases or tumors at the initial stages. PMID:23815852

  20. Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent

    PubMed Central

    Keswani, Rahul K.; Tian, Chao; Peryea, Tyler; Girish, Gandikota; Wang, Xueding; Rosania, Gus R.

    2016-01-01

    Photoacoustic Tomography (PAT) is a deep-tissue imaging modality, with potential clinical applications in the diagnosis of arthritis, cancer and other disease conditions. Here, we identified Clofazimine (CFZ), a red-pigmented dye and anti-inflammatory FDA-approved drug, as a macrophage-targeting photoacoustic (PA) imaging agent. Spectroscopic experiments revealed that CFZ and its various protonated forms yielded optimal PAT signals at wavelengths −450 to 540 nm. CFZ’s macrophage-targeting chemical and structural forms were detected with PA microscopy at a high contrast-to-noise ratio (CNR > 22 dB) as well as with macroscopic imaging using synthetic gelatin phantoms. In vivo, natural and synthetic CFZ formulations also demonstrated significant anti-inflammatory activity. Finally, the injection of CFZ was monitored via a real-time ultrasound-photoacoustic (US-PA) dual imaging system in a live animal and clinically relevant human hand model. These results demonstrate an anti-inflammatory drug repurposing strategy, while identifying a new PA contrast agent with potential applications in the diagnosis and treatment of arthritis. PMID:27000434

  1. Photoacoustic microscopy using Evans Blue dye as a contrast agent

    NASA Astrophysics Data System (ADS)

    Yao, Junjie; Maslov, Konstantin I.; Hu, Song; Wang, Lihong V.

    2010-02-01

    Complete and continuous imaging of microvascular networks is crucial for a wide variety of biomedical applications. Photoacoustic tomography can provide high resolution microvascular imaging using hemoglobin within red blood cells (RBC) as an endogenous contrast agent. However, intermittent RBC flow in capillaries results in discontinuous and fragmentary capillary images. To overcome this problem, we used Evans Blue (EB) dye as a contrast agent for in vivo photoacoustic imaging. EB has strong optical absorption at 610 nm and distributes uniformly in the blood stream by chemically binding to albumin. By intravenous injection of EB (6%, 200 μL), complete and continuous microvascular networks-especially capillaries-of the ears of nude mice were imaged. The diffusion of EB (3%, 100 μL) leaving the blood stream was monitored for 2 hours. At lower administration dose of EB (3%, 50 μL), the clearance of the EB-albumin complex was imaged for 10 days and quantitatively investigated using a two-compartment model.

  2. Characterization of liposomes containing iodine-125-labeled radiographic contrast agents

    SciTech Connect

    Zalutsky, M.R.; Noska, M.A.; Seltzer, S.E.

    1987-02-01

    Multilamellar liposomes were prepared containing either iodine-125-labeled (/sup 125/I) diatrizoate or /sup 125/I labeled iotrol in their aqueous phase. The in vitro permeabilities of liposomes containing both contrast agents were measured in the presence of saline and serum at 37 degrees C. Two different phospholipid compositions were studied: phosphatidylcholine/cholesterol/stearylamine (PC/C/S, 8: 1:1 molar ratio) and distearoylphosphatidylcholine/sphingomyelin (DSPC/SM, 5:2 mole ratio). In saline, similar permeabilities were observed for the four phospholipid-contrast agent combinations. In serum, however, leakage of /sup 125/I activity was 2 to 3 times greater from PC/C/S liposomes than from vesicles composed of DSPC/SM. When PC/C/S liposomes that contained /sup 125/I-diatrizoate were injected into rats, the clearance half-times for /sup 125/I activity from the liver, spleen, and whole body were 4.4 hours, 4.5 hours, and 2.8 hours, respectively. Liposomes composed of DSPC/SM cleared at a significantly slower rate from the liver, spleen, and whole body with half-times of 24.0 hours, 18.4 hours, and 17.2 hours observed from these tissues, respectively.

  3. Repositioning Clofazimine as a Macrophage-Targeting Photoacoustic Contrast Agent.

    PubMed

    Keswani, Rahul K; Tian, Chao; Peryea, Tyler; Girish, Gandikota; Wang, Xueding; Rosania, Gus R

    2016-01-01

    Photoacoustic Tomography (PAT) is a deep-tissue imaging modality, with potential clinical applications in the diagnosis of arthritis, cancer and other disease conditions. Here, we identified Clofazimine (CFZ), a red-pigmented dye and anti-inflammatory FDA-approved drug, as a macrophage-targeting photoacoustic (PA) imaging agent. Spectroscopic experiments revealed that CFZ and its various protonated forms yielded optimal PAT signals at wavelengths -450 to 540 nm. CFZ's macrophage-targeting chemical and structural forms were detected with PA microscopy at a high contrast-to-noise ratio (CNR > 22 dB) as well as with macroscopic imaging using synthetic gelatin phantoms. In vivo, natural and synthetic CFZ formulations also demonstrated significant anti-inflammatory activity. Finally, the injection of CFZ was monitored via a real-time ultrasound-photoacoustic (US-PA) dual imaging system in a live animal and clinically relevant human hand model. These results demonstrate an anti-inflammatory drug repurposing strategy, while identifying a new PA contrast agent with potential applications in the diagnosis and treatment of arthritis. PMID:27000434

  4. Micro-radiography of biological samples with medical contrast agents

    NASA Astrophysics Data System (ADS)

    Dammer, J.; Weyda, F.; Benes, J.; Sopko, V.; Gelbic, I.

    2013-12-01

    Micro-radiography is an imaging technique that uses X-rays to study the internal structures of objects. This fast and easy imaging tool is based on differential X-ray attenuation by various tissues and structures within biological samples. The experimental setup described is based on the semiconductor pixel X-ray detector Medipix2 and X-ray micro-focus tube. Our micro-radiographic system has been recently used not only for the examination of internal structures of various arthropods and other biological objects but also for tracing some processes in selected model species (we used living larvae of mosquito Culex quinquefasciatus). Low concentrations of iodine, lanthanum or gold particles were used as a tracer (contrast agent). Such contrast agents increase the absorption of X-rays and allow a better visibility of internal structures of model organisms (especially the various cavities, pores, etc.). In addition, the movement of tracers in selected timing experiments demonstrates some physiological functions of digestive and excretory system.

  5. Chemical warfare agents: estimating oral reference doses.

    PubMed

    Opresko, D M; Young, R A; Faust, R A; Talmage, S S; Watson, A P; Ross, R H; Davidson, K A; King, J

    1998-01-01

    Health risk assessments for sites contaminated with chemical warfare agents require a comparison of the potential levels of exposure with a characterization of the toxic potency of each chemical. For noncancer health effects, toxic potency is expressed in terms of Reference Doses (RfD). A RfD is a daily exposure level or dose (usually expressed in units of milligrams of chemical per kilogram body weight per day) for the human population, including sensitive subpopulations, that is likely to be without an appreciable risk of deleterious effects. A daily exposure at or below the RfD is not likely to be associated with health risks, but as the amount of chemical that an individual is exposed to increases above the RfD, the probability that an adverse effect will occur also increases. A RfD is derived by first examining the available human or animal toxicity data to identify a dose or exposure that corresponds to a no-observed-adverse-effect level (NOAEL) or a lowest-observed-adverse-effect level (LOAEL). The NOAEL is the exposure level at which there are no statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. Effects may be produced at this level, but they are not considered to be adverse if they do not result in functional impairment or pathological lesions that affect the performance of the whole organism or which reduce an organism's ability to cope with additional challenge. The LOAEL is the lowest exposure level at which there are statistically or biologically significant increases in frequency or severity of adverse effects between the exposed population and its appropriate control. If only a LOAEL is identified by the toxicity data, a NOAEL is estimated by dividing the LOAEL by a factor no greater than 10. This extrapolation factor of 10 or less is termed the LOAEL-to-NOAEL Uncertainty Factor (UFL). The NOAEL is also adjusted by the application of other

  6. A phase contrast cytomorphometric study of squames of normal oral mucosa and oral leukoplakia: Original study

    PubMed Central

    Nadaf, Afreen; Bavle, Radhika M; Thambiah, Lalita J; Paremala, K; Sudhakara, M; Soumya, M

    2014-01-01

    Oral leukoplakia represents the most common potentially malignant oral disorder, representing 85% of such lesions. The worldwide prevalence of leukoplakia is 1.5- 4.3%. Leukoplakia is often associated with carcinogenic exposures, such as from use of tobacco, alcohol or betel nut. The level of risk for malignant transformation of leukoplakia is associated with lesion histology. The overall malignant transformation rates for dysplastic lesions range from 11% to 36%, depending on the length of follow-up. Exfoliative cytology is a simple and minimally invasive method. Phase contrast microscope, an essential tool in the field of biology and medical research provides improved discrimination of cellular details. Aims: To study and compare the cytomorphological and cytomorphometric features of squames obtained from the mucosa of normal individuals, tobacco habituates with and without clinically evident leukoplakia. To assess the role of phase contrast microscopy as an alternative and easy method of cytological evaluation of wet and unstained smears. Materials and Methods: Fifty cases from each group were taken. Fixed, unstained smears were viewed under phase contrast microscope and were evaluated morphologically and morphometrically for nuclear and cellular diameters. Results: The study showed a significant increase in the mean nuclear diameter and decrease in the mean cellular diameter. Conclusion: Cytomorphometric changes could be the earliest indicators of cellular alterations. This indicates that there could be a cause-effect relationship between tobacco and quantitative alterations. PMID:25364176

  7. Characterizing Galbumin as a high molecular weight contrast agent in MRI - A novel dual contrast agent protocol

    NASA Astrophysics Data System (ADS)

    Moosvi, Firas; Reinsberg, Stefan; Baker, Jennifer

    2009-05-01

    In studying cancer and tumours, traditional biochemical methods call for analyzing frozen cross sections of tumour tissues, staining and then fluorescently imaging them at high resolution. While this method has served its purpose for decades, situations and conditions are arising that require dynamic imaging in live animals. Recent advances in the field of Biophysics have allowed researchers the ability to correlate images taken with Magnetic Resonance Imaging (MRI) to those using high- resolution fluorescent microscopy. While live imaging is possible using MRI, it is certainly not possible to reproduce much of the biologically relevant data acquired by fluorescent microscopy. In this proposal, we set the stage for the biological problem, cover some basic tumour biology then outline the basic principles of imaging with NMR. Finally, we characterize the use of a new contrast agent, Galbumin, to conduct a pilot study for a new class of animal MRI experiments.Finally, we present a novel protocol for a dual contrast agent MR protocol to extract permeability and flow information to improve characterization of drug delivery. Our over-arching goal is to use the live imaging capabilities of MR, and combine them with traditional fluorescent microscopy techniques to get a more accurate biological picture of a tumour.

  8. Cellulose nanoparticles: photoacoustic contrast agents that biodegrade to simple sugars

    NASA Astrophysics Data System (ADS)

    Jokerst, Jesse V.; Bohndiek, Sarah E.; Gambhir, Sanjiv S.

    2014-03-01

    In photoacoustic imaging, nanoparticle contrast agents offer strong signal intensity and long-term stability, but are limited by poor biodistribution and clearance profiles. Conversely, small molecules offer renal clearance, but relatively low photoacoustic signal. Here we describe a cellulose-based nanoparticle with photoacoustic signal superior to gold nanorods, but that undergoes enzymatic cleavage into constituent glucose molecules for renal clearance. Cellulose nanoparticles (CNPs) were synthesized through acidic cleavage of cellulose linters and purified with centrifugation. TEM indicated that the nanoparticles were 132 +/- 46 nm; the polydispersity index was 0.138. Ex vivo characterization showed a photoacoustic limit of detection of 0.02 mg/mL CNPs, and the photoacoustic signal of CNPs was 1.5- to 3.0-fold higher than gold nanorods (also at 700 nm resonance) on a particle-to-particle basis. Cell toxicity assays suggested that overnight doses below 0.31 mg/mL CNPs produced no significant (p>0.05) impact on cell metabolism. Intravenous doses up to 0.24 mg were tolerated well in nude mice. Subcutaneous and orthotopic tumor xenografts of the OV2008 ovarian cancer cell line were then created in nude mice. Data was collected with a Nexus128 scanner from Endra LifeSciences. Spectral data used a LAZR system from Visualsonics both at 700 nm excitation. We injected CNPs (0.024 mg, 0.048 mg, and 0.80 mg) via tail vein and showed that the tumor photoacoustic signal reached maximum increase between 10 and 20 minutes. All injected concentrations were statistically (p<0.05) elevated relative to the control group with n=3 mice in each group, and dose and signal had a linear relationship at R2>0.96 suggesting quantitative signal. CNP biodegradation was demonstrated ex vivo with a glucose assay. CNPs in the presence of cellulase were reduced to free glucose in under than four hours. The glucose concentration before addition of cellulase was not detectable, but increased to

  9. Biological in situ characterization of polymeric microbubble contrast agents.

    PubMed

    Wan, Sha; Egri, Gabriella; Oddo, Letizia; Cerroni, Barbara; Dähne, Lars; Paradossi, Gaio; Salvati, Anna; Lynch, Iseult; Dawson, Kenneth A; Monopoli, Marco P

    2016-06-01

    Polymeric microbubbles (MBs) are gas filled particles composed of a thin stabilized polymer shell that have been recently developed as valid contrast agents for the combined use of ultrasonography (US), magnetic resonance imaging (MRI) and single photon emission computer tomography (SPECT) imaging. Due to their buoyancy, the commonly available approaches to study their behaviour in complex media are not easily applicable and their use in modern medicine requires such behaviour to be fully elucidated. Here we have used for the first time flow cytometry as a new high throughput approach that allows characterisation of the MB dispersion, prior to and after exposure in different biological media and we have additionally developed a method that allows characterisation of the strongly bound proteins adsorbed on the MBs, to fully predict their biological behaviour in biological milieu. PMID:26993210

  10. Superparamagnetic FePt nanoparticles as excellent MRI contrast agents

    NASA Astrophysics Data System (ADS)

    Maenosono, Shinya; Suzuki, Toshimasa; Saita, Soichiro

    Chemically disordered face-centered cubic (fcc) FePt nanoparticles (NPs) with a mean diameter of 9 nm were synthesized via pyrolysis of iron(III) ethoxide and platinum(II) acetylacetonate. The surface ligands of these NPs were then exchanged from oleic acid to tetramethylammonium hydroxide (TMAOH) to measure the longitudinal ( T1) and transverse ( T2) proton relaxation times of aqueous dispersion of FePt NPs. Magnetic resonance relaxometry reveals that TMAOH-capped FePt NPs have a higher T2-shortening effect than conventional superparamagnetic iron oxide NPs, indicating that fcc-phase FePt NPs might be superior negative contrast agents for magnetic resonance imaging.

  11. Biodistribution of gadolinium-based contrast agents, including gadolinium deposition

    PubMed Central

    Aime, Silvio; Caravan, Peter

    2010-01-01

    The biodistribution of approved gadolinium (Gd) based contrast agents (GBCA) is reviewed. After intravenous injection GBCA distribute in the blood and the extracellular space and transiently through the excretory organs. Preclinical animal studies and the available clinical literature indicate that all these compounds are excreted intact. Elimination tends to be rapid and for the most part, complete. In renally insufficient patients the plasma elimination half-life increases substantially from hours to days depending on renal function. In patients with impaired renal function and nephrogenic systemic fibrosis (NSF), the agents gadodiamide, gadoversetamide, and gadopentetate dimeglumine have been shown to result in Gd deposition in the skin and internal organs. In these cases, it is likely that the Gd is no longer present as the GBCA, but this has still not been definitively shown. In preclinical models very small amounts of Gd are retained in the bone and liver, and the amount retained correlates with the kinetic and thermodynamic stability of the GBCA with respect to Gd release in vitro. The pattern of residual Gd deposition in NSF subjects may be different than that observed in preclinical rodent models. GBCA are designed to be used via intravenous administration. Altering the route of administration and/or the formulation of the GBCA can dramatically alter the biodistribution of the GBCA and can increase the likelihood of Gd deposition. PMID:19938038

  12. Mechanically Tunable Hollow Silica Ultrathin Nanoshells for Ultrasound Contrast Agents

    PubMed Central

    Liberman, A.; Wang, J.; Lu, N.; Viveros, R.D.; Allen, C. A.; Mattrey, R.F.; Blair, S.L.; Trogler, W.C.; Kim, M. J.; Kummel, A.C.

    2015-01-01

    Perfluoropentane (PFP) gas filled biodegradable iron-doped silica nanoshells have been demonstrated as long-lived ultrasound contrast agents. Nanoshells are synthesized by a sol-gel process with tetramethyl orthosilicate (TMOS) and iron ethoxide. Substituting a fraction of the TMOS with R-substituted trialkoxysilanes produces ultrathin nanoshells with varying shell thicknesses and morphologies composed of fused nanoflakes. The ultrathin nanoshells had continuous ultrasound Doppler imaging lifetimes exceeding 3 hours, were twice as bright using contrast specific imaging, and had decreased pressure thresholds compared to control nanoshells synthesized with just TMOS. Transmission electron microscopy (TEM) showed that the R-group substituted trialkoxysilanes could reduce the mechanically critical nanoshell layer to 1.4 nm. These ultrathin nanoshells have the mechanical behavior of weakly linked nanoflakes but the chemical stability of silica. The synthesis can be adapted for general fabrication of three-dimensional nanostructures composed of nanoflakes, which have thicknesses from 1.4–3.8 nm and diameters from 2–23 nm. PMID:26955300

  13. Optical contrast agents to visualize molecular expression in breast cancer

    NASA Astrophysics Data System (ADS)

    Langsner, Robert James

    Breast cancer is the second leading cause of death of women in the United States. Improvements in screening technology have increased the breast cancer incidence rate, as smaller lesions are being detected. Due to the small size of lesions, patients can choose to receive breast conservation therapy (BCT) rather than a modified radical mastectomy. Even though the breast retains cosmesis after BCT, there is an increased risk of the patient having residual microscopic disease, known as positive margins. Patients with positive margins receive increased radiation and have an increased chance of second surgery. Pathology with hematoxylin and eosin (H&E) remains the gold standard for diagnosing margin status in patients. Intraoperative pathology has been shown to reduce the rate of positive margins in BCT. However, a minority of surgery centers have intraoperative pathology centers, limiting the number of patients that receive this standard of care. The expression profiles of surface receptors such as ErbB2 (HER2-positive) and epidermal growth factor receptor (EGFR) provide information about the aggressiveness of a particular tumor. Recent research has shown that there was elevated EGFR expression in patients with a local recurrence even though the biopsies were assessed to be disease free using standard H&E. If the physicians had known the molecular expression of these biopsies, a different treatment regimen or excision of more tissue might have prevented the recurrence. This thesis investigates targeted molecular contrast agents that enhance the visualization of molecular markers such as glucose transporters (GLUTs) and growth factor receptors in tissue specimens. First, application of 2-NBDG, a fluorescent deoxyglucose, enhances signal in cancerous tissue with a 20-minute incubation. Then, antibody functionalized silica-gold nanoshells enhance the visualization of ErbB2 overexpression in specimens with a 5-minute incubation. To image these contrast agents in cancerous

  14. Section 6—Mechanical Bioeffects in the Presence of Gas-Carrier Ultrasound Contrast Agents

    PubMed Central

    2007-01-01

    This review addresses the issue of mechanical ultrasound-induced bioeffects in the presence of gas carrier contrast agents (GCAs). Here, the term “contrast agent” refers to those agents that provide ultrasound contrast by being composed of microbubbles, encapsulated or not, containing one or more gases. Provided in this section are summaries on how contrast agents work, some of their current uses, and the potential for bio-effects associated with their presence in an ultrasonic field. PMID:10680618

  15. [Immediate allergy to iodinated contrast agents and prevention of reactions].

    PubMed

    Dewachter, P; Mouton-Faivre, C; Laroche, D; Clément, O

    2009-10-01

    The incidence and morbimortality of immediate hypersensitivity reactions following iodinated contrast media (ICM) injection remain unknown. The diagnosis of an immediate hypersensitivity reaction relies on a triad associating the precise description of the initial clinical manifestations and their delay of onset, the results of the biological assessment performed after the reaction including histamine and tryptase serum level measurements, and the results of skin testing with the culprit agent. Analysis of these data allows identification of the pathophysiologic mechanism of the reaction and the allergen involved in case of allergic hypersensitivity. Skin tests should be performed according to strict criteria. Cross-reactivity with ICM has to be investigated in order to propose a nonreactive ICM for future procedures. Allergic hypersensitivity to a given ICM imposes its definitive avoidance but not the avoidance of all iodinated drugs. The allergenic sequence has not yet been identified but is not the iodine atom itself. Asthma and treatment with beta-blockers are not risk factors of immediate allergic reactions to ICM per se, but may increase their severity. The various published protocols of premedication do not prevent the occurrence of an allergic/anaphylactic reaction to an ICM. The avoidance of the culprit ICM is the only way to prevent further reactions. PMID:19375199

  16. Ultrasound Induced Fluorescence of Nanoscale Liposome Contrast Agents

    PubMed Central

    Zhang, Qimei; Morgan, Stephen P.; O’Shea, Paul; Mather, Melissa L.

    2016-01-01

    A new imaging contrast agent is reported that provides an increased fluorescent signal upon application of ultrasound (US). Liposomes containing lipids labelled with pyrene were optically excited and the excimer fluorescence emission intensity was detected in the absence and presence of an ultrasound field using an acousto-fluorescence setup. The acousto-fluorescence dynamics of liposomes containing lipids with pyrene labelled on the fatty acid tail group (PyPC) and the head group (PyPE) were compared. An increase in excimer emission intensity following exposure to US was observed for both cases studied. The increased intensity and time constants were found to be different for the PyPC and PyPE systems, and dependent on the applied US pressure and exposure time. The greatest change in fluorescence intensity (130%) and smallest rise time constant (0.33 s) are achieved through the use of PyPC labelled liposomes. The mechanism underlying the observed increase of the excimer emission intensity in PyPC labelled liposomes is proposed to arise from the “wagging” of acyl chains which involves fast response and requires lower US pressure. This is accompanied by increased lipid lateral diffusivity at higher ultrasound pressures, a mechanism that is also active in the PyPE labelled liposomes. PMID:27467748

  17. BROADBAND ATTENUATION MEASUREMENTS OF PHOSPHOLIPID-SHELLED ULTRASOUND CONTRAST AGENTS

    PubMed Central

    Raymond, Jason L.; Haworth, Kevin J.; Bader, Kenneth B.; Radhakrishnan, Kirthi; Griffin, Joseph K.; Huang, Shao-Ling; McPherson, David D.; Holland, Christy K.

    2014-01-01

    The aim of this study was to characterize the frequency-dependent acoustic attenuation of three phospholipid-shelled ultrasound contrast agents (UCAs): Definity, MicroMarker and echogenic liposomes. A broadband through-transmission technique allowed for measurement over 2 to 25 MHz with a single pair of transducers. Viscoelastic shell parameters of the UCAs were estimated using a linearized model developed by N. de Jong, L. Hoff, T. Skotland and N. Bom (Ultrasonics 1992; 30:95–103). The effect of diluent on the attenuation of these UCA suspensions was evaluated by performing attenuation measurements in 0.5% (w/v) bovine serum albumin and whole blood. Changes in attenuation and shell parameters of the UCAs were investigated at room temperature (25°C) and physiologic temperature (37°C). The attenuation of the UCAs diluted in 0.5% (w/v) bovine serum albumin was found to be identical to the attenuation of UCAs in whole blood. For each UCA, attenuation was higher at 37°C than at 25°C, underscoring the importance of conducting characterization studies at physiologic temperature. Echogenic liposomes exhibited a larger increase in attenuation at 37°C versus 25°C than either Definity or MicroMarker. PMID:24262056

  18. Demonstration of a Sucrose-derived Contrast Agent for Magnetic Resonance Imaging of the GI Tract

    PubMed Central

    Martinez, Gary V.; Navath, Suryakiran; Sewda, Kamini; Rao, Venkataramanarao; Foroutan, Parastou; Alleti, Ramesh; Moberg, Valerie E.; Ahad, Ali M.; Coppola, Domenico; Lloyd, Mark C.; Gillies, Robert J.; Morse, David L.; Mash, Eugene A.

    2013-01-01

    A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd-DOTA complex were attached via copper(I)-catalyzed azide-alkyne cycloaddition. The resulting contrast agent (CA) was administered by gavage to C3H mice. Passage of the CA through the gastrointestinal (GI) tract was followed by T1-weighted magnetic resonance imaging (MRI) over a period of 47 hours, by which time the CA had exited the GI tract. No evidence for leakage of the CA from the GI tract was observed. Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated. PMID:23481651

  19. Demonstration of a sucrose-derived contrast agent for magnetic resonance imaging of the GI tract.

    PubMed

    Martinez, Gary V; Navath, Suryakiran; Sewda, Kamini; Rao, Venkataramanarao; Foroutan, Parastou; Alleti, Ramesh; Moberg, Valerie E; Ahad, Ali M; Coppola, Domenico; Lloyd, Mark C; Gillies, Robert J; Morse, David L; Mash, Eugene A

    2013-04-01

    A scaffold bearing eight terminal alkyne groups was synthesized from sucrose, and copies of an azide-terminated Gd-DOTA complex were attached via copper(I)-catalyzed azide-alkyne cycloaddition. The resulting contrast agent (CA) was administered by gavage to C3H mice. Passage of the CA through the gastrointestinal (GI) tract was followed by T1-weighted magnetic resonance imaging (MRI) over a period of 47h, by which time the CA had exited the GI tract. No evidence for leakage of the CA from the GI tract was observed. Thus, a new, orally administered CA for MRI of the GI tract has been developed and successfully demonstrated. PMID:23481651

  20. Small-animal microangiography using phase-contrast X-ray imaging and gas as contrast agent

    NASA Astrophysics Data System (ADS)

    Lundström, Ulf; Larsson, Daniel H.; Westermark, Ulrica K.; Burvall, Anna; Hertz, Hans M.

    2014-03-01

    We use propagation-based phase-contrast X-ray imaging with gas as contrast agent to visualize the microvasculature in small animals like mice and rats. The radiation dose required for absorption X-ray imaging is proportional to the minus fourth power of the structure size to be detected. This makes small vessels impossible to image at reasonable radiation doses using the absorption of conventional iodinated contrast agents. Propagation-based phase contrast gives enhanced contrast for high spatial frequencies by moving the detector away from the sample to let phase variations in the transmitted X-rays develop into intensity variations at the detector. Blood vessels are normally difficult to observe in phase contrast even with iodinated contrast agents as the density difference between blood and most tissues is relatively small. By injecting gas into the blood stream this density difference can be greatly enhanced giving strong phase contrast. One possible gas to use is carbon dioxide, which is a clinically accepted X-ray contrast agent. The gas is injected into the blood stream of patients to temporarily displace the blood in a region and thereby reduce the X-ray absorption in the blood vessels. We have shown that this method can be used to image blood vessels down to 8 μm in diameter in mouse ears. The low dose requirements of this method indicate a potential for live small-animal imaging and longitudinal studies of angiogenesis.

  1. Complex interfaces in "phase-change" contrast agents.

    PubMed

    Capece, Sabrina; Domenici, Fabio; Brasili, Francesco; Oddo, Letizia; Cerroni, Barbara; Bedini, Angelico; Bordi, Federico; Chiessi, Ester; Paradossi, Gaio

    2016-03-28

    In this paper we report on the study of the interface of hybrid shell droplets encapsulating decafluoropentane (DFP), which exhibit interesting potentialities for ultrasound (US) imaging. The fabrication of the droplets is based on the deposition of a dextran methacrylate layer onto the surface of surfactants. The droplets have been stabilized against coalescence by UV curing, introducing crosslinks in the polymer layer and transforming the shell into an elastomeric membrane with a thickness of about 300 nm with viscoelastic behaviour. US irradiation induces the evaporation of the DFP core of the droplets transforming the particles into microbubbles (MBs). The presence of a robust crosslinked polymer shell introduces an unusual stability of the droplets also during the core phase transition and allows the recovery of the initial droplet state after a few minutes from switching off US. The interfacial tension of the droplets has been investigated by two approaches, the pendant drop method and an indirect method, based on the determination of the liquid ↔ gas transition point of DFP confined in the droplet core. The re-condensation process has been followed by capturing images of single MBs by confocal microscopy. The time evolution of MB relaxation to droplets was analysed in terms of a modified Church model to account for the structural complexity of the MB shell, i.e. a crosslinked polymer layer over a layer of surfactants. In this way the microrheology parameters of the shell were determined. In a previous paper (Chem. Commun., 2013, 49, 5763-5765) we showed that these systems could be used as ultrasound contrast agents (UCAs). In this work we substantiate this view assessing some key features offered by the viscoelastic nature of the droplet shell. PMID:26931337

  2. Novel oral anticoagulants and reversal agents: Considerations for clinical development.

    PubMed

    Sarich, Troy C; Seltzer, Jonathan H; Berkowitz, Scott D; Costin', James; Curnutte, John T; Gibson, C Michael; Hoffman, Maureane; Kaminskas, Edvardas; Krucoff, Mitchell W; Levy, Jerrold H; Mintz, Paul D; Reilly, Paul A; Sager, Philip T; Singer, Daniel E; Stockbridge, Norman; Weitz, Jeffrey I; Kowey, Peter R

    2015-06-01

    This white paper provides a summary of presentations and discussions that were held at an Anticoagulant-Induced Bleeding and Reversal Agents Think Tank co-sponsored by the Cardiac Safety Research Consortium and the US Food and Drug Administration (FDA) at the FDA's White Oak Headquarters on April 22, 2014. Attention focused on a development pathway for reversal agents for the novel oral anticoagulants (NOACs). This is important because anticoagulation is still widely underused for stroke prevention in patients with atrial fibrillation. Undertreatment persists, although NOACs, in general, overcome some of the difficulties associated with anticoagulation provided by vitamin K antagonists. One reason for the lack of a wider uptake is the absence of NOAC reversal agents. As there are neither widely accepted academic and industry standards nor a definitive regulatory policy on the development of such reversal agents, this meeting provided a forum for leaders in the fields of cardiovascular clinical trials and cardiovascular safety to discuss the issues and develop recommendations. Attendees included representatives from pharmaceutical companies; regulatory agencies; end point adjudication specialist groups; contract research organizations; and active, academically based physicians. There was wide and solid consensus that NOACs overall offer improvements in convenience, efficacy, and safety compared with warfarin, even without reversal agents. Still, it was broadly accepted that it would be helpful to have reversal agents available for clinicians to use. Because it is not feasible to do definitive outcomes studies demonstrating a reversal agent's clinical benefits, it was felt that these agents could be approved for use in life-threatening bleeding situations if the molecules were well characterized preclinically, their pharmacodynamic and pharmacokinetic profiles were well understood, and showed no harmful adverse events in early human testing. There was also consensus

  3. Experimental characterization, comparison and image quality assessment of two ultrasound contrast agents: Optison and Definity

    NASA Astrophysics Data System (ADS)

    Hughes, Amy C.; Day, Steven W.; Linte, Cristian A.; Schwarz, Karl Q.

    2016-04-01

    Microbubble-based contrast agents are commonly used in ultrasound imaging to help differentiate the blood pool from the endocardial wall. It is essential to use an agent which produces high image intensity relative to the surrounding tissue, commonly referred to contrast effect. When exposed to ultrasound waves, microbubbles produce an intense backscatter signal in addition to the contrast produced by the fluctuating size of the microbubbles. However, over time, the microbubble concentration depletes, leading to reduced visual enhancement. The retention time associated with contrast effect varies according to the frequency and power level of the ultrasound wave, as well as the contrast agent used. The primary objective of this study was to investigate and identify the most appropriate image acquisition parameters that render optimal contrast effect for two intravenous contrast agents, Optison™ and Definity™. Several controlled in vitro experiments were conducted using an experimental apparatus that featured a perfused tissue-emulating phantom. A continuous flow of contrast agent was imaged using ultrasound at different frequencies and power levels, while a pulse wave Doppler device was used to monitor the concentration of the contrast agent solution. The contrast effect was determined based on the image intensity inside the flow pipe mimicking the blood-pool relative to the intensity of the surrounding phantom material mimicking cardiac tissue. To identify the combination of parameters that yielded optimal visualization for each contrast agent tested, the contrast effect was assessed at different microbubble concentrations and different ultrasound imaging frequencies and transmission power levels.

  4. Active extravasation of gadolinium-based contrast agent into the subdural space following lumbar puncture.

    PubMed

    Kothari, Pranay D; Hanser, Evelyn M; Wang, Harrison; Farid, Nikdokht

    2016-01-01

    A 38year-old male presented with cauda equina syndrome following multiple lumbar puncture attempts. Lumbar spine magnetic resonance imaging (MRI) showed a subdural hematoma and an area of apparent contrast enhancement in the spinal canal on sagittal post-contrast images. Axial post-contrast images obtained seven minutes later demonstrated an increase in size and change in shape of the region of apparent contrast enhancement, indicating active extravasation of the contrast agent. This is the first reported case of active extravasation of gadolinium-based contrast agent in the spine. PMID:27317202

  5. AParadigm Shift: The New Novel Oral Anticoagulation Agents.

    PubMed

    Saeed, Wajeeha; Burke, James F; Mirrani, Ghazi; Sirinivasa, Minisha; Nabi, Usman; Hayat, Umar; Khan, Zubair; Sardar, Muhammad Rizwan

    2016-07-01

    Atrial fibrillation (AF) is the most common arrhythmia and represents one-third of the arrhythmia-related hospital admissions in the developed countries. Embolic strokes associated with AF are more severe and disabling. Thromboembolic stroke prevention is a major goal in treatment of AF and Warfarin has successfully served this purpose for many years. Drug-drug interaction and regular monitoring with Warfarin pose a significant challenge where health care system has limited resources; and lack of a well-structured health system, hinders regular International Normalized Ratio (INR) monitoring. Novel oral anticoagulants (NOACs) have opened up a new exciting chapter in the field of anticoagulation in non-valvular atrial fibrillation (NVAF). This review discussed the landmark trials that led to the development of NOACs and explored the potentials of these new agents with simultaneous comparison of Warfarin. PMID:27504556

  6. Engineering of Nanoscale Contrast Agents for Optical Coherence Tomography

    PubMed Central

    Gordon, Andrew Y; Jayagopal, Ashwath

    2014-01-01

    Optical coherence tomography has emerged as valuable imaging modalityin ophthalmology and other fields by enabling high-resolution three-dimensional imaging of tissue. In this paper, we review recent progress in the field of contrast-enhanced optical coherence tomography (OCT). We discuss exogenous and endogenous sources of OCT contrast, focusing on their use with standard OCT systems as well as emerging OCT-based imaging modalities. We include advances in the processing of OCT data that generate improved tissue contrast, including spectroscopic OCT (SOCT), as well as work utilizing secondary light sources and/or detection mechanisms to create and detect enhanced contrast, including photothermal OCT (PTOCT) and photoacoustic OCT (PAOCT). Finally, we conclude with a discussion of the translational potential of these developments as well as barriers to their clinical use. PMID:25009761

  7. Adherence of oral streptococci to an immobilized antimicrobial agent.

    PubMed

    Saito, T; Takatsuka, T; Kato, T; Ishihara, K; Okuda, K

    1997-08-01

    An antimicrobial agent, 3-(trimethoxysilyl)-propyldimethyloctadecyl ammonium chloride, was immobilized on silica. Interaction between the material (termed) OAIS) and various oral bacterial species were then studied. Seven species of Streptococcus and two Actinomyces were investigated for their ability to adhere to this biomaterial. Cell-surface hydrophobicity and zeta-potential were examined as well. Analysis of extracted hydrophobic proteins which adhered to OAIS revealed that the adherence of these micro-organisms was closely related to the hydrophobicity of their cell surfaces. The results of zeta-potential assays indicated that negative charge on the cell surface inhibited adherence to OAIS. Gel electrophoresis revealed that OAIS could absorb cell-surface hydrophobic proteins from all bacterial species tested. Preadsorption of hydrophobic components on the cell surface inhibited adherence of the Strep. mutans strain to OAIS in a dose-dependent manner. The results indicate that OAIS adsorption of these oral bacteria was dependent on the degree of hydrophobicity of their surfaces. A major component of this adherence was hydrophobic cell-surface proteins. PMID:9347116

  8. Intravascular contrast agent improves magnetic resonance angiography of carotid arteries in minipigs.

    PubMed

    Lin, W; Abendschein, D R; Celik, A; Dolan, R P; Lauffer, R B; Walovitch, R C; Haacke, E M

    1997-01-01

    This study was designed to optimize three-dimensional (3D) time-of-flight (TOF) magnetic resonance angiography (MRA) sequences and to determine whether contrast-enhanced MRA could improve the accuracy of lumen definition in stenosed carotid arteries of minipigs. 3D TOF MRA was acquired with use of either an intravascular (n = 13) and/or an extravascular contrast agent (n = 5) administrated at 2 to 4 weeks after balloon-induced injury to a carotid artery in 16 minipigs. Vascular contrast, defined as signal intensity differences between blood vessels and muscle normalized to the signal intensity of muscle, was compared before and after the injection of each contrast agent and between the two agents. Different vascular patencies were observed among the animals, including completely occluded vessels (n = 5), stenotic vessels (n = 3), and vessels with no visible stenosis (n = 8). Superior vascular contrast improvement was observed for small arteries and veins and for large veins with the intravascular contrast agent when compared with the extravascular contrast agent. In addition, preliminary studies in two of the animals showed a good correlation for the extent of luminal stenosis defined by digital subtraction angiography compared with MRA obtained after administration of the intravascular contrast agent (R2 = .71, with a slope of .96 +/- .04 by a linear regression analysis). We concluded that use of an intravascular contrast agent optimizes 3D TOF MRA and may improve its accuracy compared with digital subtraction angiography. PMID:9400838

  9. Synthetic Ni3S2/Ni hybrid architectures as potential contrast agents in MRI

    NASA Astrophysics Data System (ADS)

    Ma, J.; Chen, K.

    2016-04-01

    Traditional magnetic resonance imaging (MRI) contrast agents mainly include superparamagnetic (SPM) iron oxide nanoparticle as T 2 contrast agent for liver and paramagnetic Gd (III)-chelate as T 1 contrast agent for all organs. In this work, weak ferromagnetic kale-like and SPM cabbage-like Ni3S2@Ni hybrid architectures were synthesized and evaluated as potential T 1 MRI contrast agents. Their relatively small r 2/r 1 ratios of 2.59 and 2.38, and high r 1 values of 11.27 and 4.89 mmol‑1 L s‑1 (for the kale-like and cabbage-like Ni3S2@Ni, respectively) will shed some light on the development of new-type MRI contrast agents.

  10. X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents.

    PubMed

    Rand, Danielle; Uchida, Masaki; Douglas, Trevor; Rose-Petruck, Christoph

    2014-09-22

    Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based "nanobubble" contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

  11. X-ray spatial frequency heterodyne imaging of protein-based nanobubble contrast agents

    PubMed Central

    Rand, Danielle; Uchida, Masaki; Douglas, Trevor; Rose-Petruck, Christoph

    2014-01-01

    Spatial Frequency Heterodyne Imaging (SFHI) is a novel x-ray scatter imaging technique that utilizes nanoparticle contrast agents. The enhanced sensitivity of this new technique relative to traditional absorption-based x-ray radiography makes it promising for applications in biomedical and materials imaging. Although previous studies on SFHI have utilized only metal nanoparticle contrast agents, we show that nanomaterials with a much lower electron density are also suitable. We prepared protein-based “nanobubble” contrast agents that are comprised of protein cage architectures filled with gas. Results show that these nanobubbles provide contrast in SFHI comparable to that of gold nanoparticles of similar size. PMID:25321797

  12. Noninvasive visualization of in vivo release and intratumoral distribution of surrogate MR contrast agent using the dual MR contrast technique.

    PubMed

    Onuki, Yoshinori; Jacobs, Igor; Artemov, Dmitri; Kato, Yoshinori

    2010-09-01

    A direct evaluation of the in vivo release profile of drugs from carriers is a clinical demand in drug delivery systems, because drug release characterized in vitro correlates poorly with in vivo release. The purpose of this study is to demonstrate the in vivo applicability of the dual MR contrast technique as a useful tool for noninvasive monitoring of the stability and the release profile of drug carriers, by visualizing in vivo release of the encapsulated surrogate MR contrast agent from carriers and its subsequent intratumoral distribution profile. The important aspect of this technique is that it incorporates both positive and negative contrast agents within a single carrier. GdDTPA, superparamagnetic iron oxide nanoparticles, and 5-fluorouracil were encapsulated in nano- and microspheres composed of poly(D,L-lactide-co-glycolide), which was used as a model carrier. In vivo studies were performed with orthotopic xenograft of human breast cancer. The MR-based technique demonstrated here has enabled visualization of the delivery of carriers, and release and intratumoral distribution of the encapsulated positive contrast agent. This study demonstrated proof-of-principle results for the noninvasive monitoring of in vivo release and distribution profiles of MR contrast agents, and thus, this technique will make a great contribution to the field. PMID:20580427

  13. Contrast Agents for Quantitative MicroCT of Lung Tumors in Mice

    PubMed Central

    Lalwani, Kush; Giddabasappa, Anand; Li, Danan; Olson, Peter; Simmons, Brett; Shojaei, Farbod; Arsdale, Todd Van; Christensen, James; Jackson-Fisher, Amy; Wong, Anthony; Lappin, Patrick B; Eswaraka, Jeetendra

    2013-01-01

    The identification and quantitative evaluation of lung tumors in mouse models is challenging and an unmet need in preclinical arena. In this study, we developed a noninvasive contrast-enhanced microCT (μCT) method to longitudinally evaluate and quantitate lung tumors in mice. Commercially available μCT contrast agents were compared to determine the optimal agent for visualization of thoracic blood vessels and lung tumors in naïve mice and in non-small-cell lung cancer models. Compared with the saline control, iopamidol and iodinated lipid agents provided only marginal increases in contrast resolution. The inorganic nanoparticulate agent provided the best contrast and visualization of thoracic vascular structures; the density contrast was highest at 15 min after injection and was stable for more than 4 h. Differential contrast of the tumors, vascular structures, and thoracic air space by the nanoparticulate agent enabled identification of tumor margins and accurate quantification. μCT data correlated closely with traditional histologic measurements (Pearson correlation coefficient, 0.995). Treatment of ELM4–ALK mice with crizotinib yielded 65% reduction in tumor size and thus demonstrated the utility of quantitative μCT in longitudinal preclinical trials. Overall and among the 3 agents we tested, the inorganic nanoparticulate product was the best commercially available contrast agent for visualization of thoracic blood vessels and lung tumors. Contrast-enhanced μCT imaging is an excellent noninvasive method for longitudinal evaluation during preclinical lung tumor studies. PMID:24326223

  14. Development and characterization of a nano-scale contrast agent.

    PubMed

    Oeffinger, Brian E; Wheatley, Margaret A

    2004-04-01

    Agents injected parenterally must be less than approximately 8 microm diameter in order to traverse the capillaries in the pulmonary bed, but these agents remain in the vasculature until they are eliminated from the body by a variety of mechanisms. Targeting of cells outside the capillaries requires agent diameters of less than approximately 700 nm to enable escape through the larger-than-usual pores that have been noted in the leaky vasculature of a tumor. The objective of this study was to test the feasibility of creating a surfactant-stabilized nano-bubble with favorable acoustic properties, and identify the key parameters that influence size, yield and stability. Size distribution was characterized using laser light scattering. In vitro acoustic enhancement was assessed by generation of dose and time response curves. We previously developed a successful protocol to generate gas-filled microbubbles (containing perfluorocarbon, sulfur hexafluoride or air) with mean diameter of 1.5 microm, using sonication of carefully selected surfactant mixtures. This presentation describes generation of nano-bubbles with mean diameters ranging from 700 to 450 nm, depending on process variables. In all cases a centrifugation step was employed to separate the nano-sized particles. The in vitro dose response curves gave a maximum of 23-27 dB enhancement compared to buffer in the absence of agent, with the maximum enhancement and presence of shadowing at higher doses being dependent on the fabrication protocol. The effect of sonication time for solutions containing a mixture of the surfactants (Span 60 and Tween 80) was also tested, but was determined not to be an influencing factor. Future studies will involve development of a mathematical model characterizing the mean size as a function of centrifugal force, spin time and initial size distribution. Future work will also include imaging of tumor-bearing mice and measuring imaging potential in vivo in New Zealand white rabbits

  15. Diffusion coefficients of articular cartilage for different CT and MRI contrast agents.

    PubMed

    Kulmala, K A M; Korhonen, R K; Julkunen, P; Jurvelin, J S; Quinn, T M; Kröger, H; Töyräs, J

    2010-10-01

    In contrast enhanced magnetic resonance imaging (MRI) and computed tomography (CT), the equilibrium distribution of anionic contrast agent is expected to reflect the fixed charged density (FCD) of articular cartilage. Diffusion is mainly responsible for the transport of contrast agents into cartilage. In osteoarthritis, cartilage composition changes at early stages of disease, and solute diffusion is most likely affected. Thus, investigation of contrast agent diffusion could enable new methods for imaging of cartilage composition. The aim of this study was to determine the diffusion coefficient of four contrast agents (ioxaglate, gadopentetate, iodide, gadodiamide) in bovine articular cartilage. The contrast agents were different in molecular size and charge. In peripheral quantitative CT experiments, penetration of contrast agent into the tissue was allowed either through the articular surface or through deep cartilage. To determine diffusion coefficients, a finite element model based on Fick's law was fitted to experimental data. Diffusion through articular surface was faster than through deep cartilage with every contrast agent. Iodide, being of atomic size, diffused into the cartilage significantly faster (q<0.05) than the other three contrast agents, for either transport direction. The diffusion coefficients of all clinical contrast agents (ioxaglate, gadopentetate and gadodiamide) were relatively low (142.8-253.7 μm(2)/s). In clinical diagnostics, such slow diffusion may not reach equilibrium and this jeopardizes the determination of FCD by standard methods. However, differences between diffusion through articular surface and deep cartilage, that are characterized by different tissue composition, suggest that diffusion coefficients may correlate with cartilage composition. Present method could therefore enable image-based assessment of cartilage composition by determination of diffusion coefficients within cartilage tissue. PMID:20594900

  16. K-edge ratio method for identification of multiple nanoparticulate contrast agents by spectral CT imaging

    PubMed Central

    Ghadiri, H; Ay, M R; Shiran, M B; Soltanian-Zadeh, H

    2013-01-01

    Objective: Recently introduced energy-sensitive X-ray CT makes it feasible to discriminate different nanoparticulate contrast materials. The purpose of this work is to present a K-edge ratio method for differentiating multiple simultaneous contrast agents using spectral CT. Methods: The ratio of two images relevant to energy bins straddling the K-edge of the materials is calculated using an analytic CT simulator. In the resulting parametric map, the selected contrast agent regions can be identified using a thresholding algorithm. The K-edge ratio algorithm is applied to spectral images of simulated phantoms to identify and differentiate up to four simultaneous and targeted CT contrast agents. Results: We show that different combinations of simultaneous CT contrast agents can be identified by the proposed K-edge ratio method when energy-sensitive CT is used. In the K-edge parametric maps, the pixel values for biological tissues and contrast agents reach a maximum of 0.95, whereas for the selected contrast agents, the pixel values are larger than 1.10. The number of contrast agents that can be discriminated is limited owing to photon starvation. For reliable material discrimination, minimum photon counts corresponding to 140 kVp, 100 mAs and 5-mm slice thickness must be used. Conclusion: The proposed K-edge ratio method is a straightforward and fast method for identification and discrimination of multiple simultaneous CT contrast agents. Advances in knowledge: A new spectral CT-based algorithm is proposed which provides a new concept of molecular CT imaging by non-iteratively identifying multiple contrast agents when they are simultaneously targeting different organs. PMID:23934964

  17. Bioengineered Colorectal Cancer Drugs: Orally Delivered Anti-Inflammatory Agents.

    PubMed

    Urbanska, Aleksandra Malgorzata; Zhang, Xiaoying; Prakash, Satya

    2015-07-01

    Intestinal inflammation is one of the major factors that increase colorectal cancer (CRC) incidence worldwide. Inflammation in the gastrointestinal tract is directly linked to tumor development at the early stages of the disease, thus a key issue toward the prevention and the treatment of colonic neoplasia. Thus, the use of anti-inflammatory drugs has emerged first as a strategy to reduce chronic inflammation in case of many inflammatory bowel diseases (IBD), but it has proven its efficacy by reducing the risk of colonic neoplasia. This comprehensive review highlights the role of chronic inflammation, mainly in IBD, in the development of CRC including molecular and immune mechanisms that have tumorigenic effects. Multiple lines of evidence indicate that several bioactive and phytochemical compounds used as anti-inflammatory drugs have also antitumoral attributes. The uses of orally delivered cytokines and small molecules, as well as key dietary supplementation as anti-inflammatory therapeutics are discussed. In addition, comprehensive knowledge about CRC and intestinal inflammation, and the importance of the intestinal mucosal wall as a mucosal immunological barrier that comes into play during interactions with gut microbiota (pathogens and commensal), luminal secretions (bile acids, and bacterial and epithelial metabolites), and ingested chemicals (food components, high fat content, heterocyclic amines, and low intake of dietary fiber) are underscored. The multifunctionality of several anti-inflammatory drugs opens a line for their application in the treatment and prevention not only in IBD but also in CRC. Current bioengineering approaches for oral delivery of anti-inflammatory agents including cytokines, genetically modified bacteria, or small molecule inhibitors of inflammation directly contribute to the early management of CRC. Limitations of the current therapeutics, which stem from the lack of complete understanding of the complex molecular interactions

  18. Diffusion and near-equilibrium distribution of MRI and CT contrast agents in articular cartilage.

    PubMed

    Silvast, Tuomo S; Kokkonen, Harri T; Jurvelin, Jukka S; Quinn, Thomas M; Nieminen, Miika T; Töyräs, Juha

    2009-11-21

    Charged contrast agents have been used both in vitro and in vivo for estimation of the fixed charge density (FCD) in articular cartilage. In the present study, the effects of molecular size and charge on the diffusion and equilibrium distribution of several magnetic resonance imaging (MRI) and computed tomography (CT) contrast agents were investigated. Full thickness cartilage disks (Ø = 4.0 mm, n = 64) were prepared from fresh bovine patellae. Contrast agent (gadopentetate: Magnevist((R)), gadodiamide: Omniscan, ioxaglate: Hexabrix or sodium iodide: NaI) diffusion was allowed either through the articular surface or through the deep cartilage. CT imaging of the samples was conducted before contrast agent administration and after 1, 5, 9, 16, 25 and 29 h (and with three samples after 2, 3, 4 and 5 days) diffusion using a clinical peripheral quantitative computed tomography (pQCT) instrument. With all contrast agents, the diffusion through the deep cartilage was slower when compared to the diffusion through the articular surface. With ioxaglate, gadopentetate and gadodiamide it took over 29 h for diffusion to reach the near-equilibrium state. The slow diffusion of the contrast agents raise concerns regarding the validity of techniques for FCD estimation, as these contrast agents may not reach the equilibrium state that is assumed. However, since cartilage composition, i.e. deep versus superficial, had a significant effect on diffusion, imaging of the nonequilibrium diffusion process might enable more accurate assessment of cartilage integrity. PMID:19864699

  19. Liver-specific agents for contrast-enhanced MRI: role in oncological imaging

    PubMed Central

    Thian, Yee Liang; Riddell, Angela M.

    2013-01-01

    Abstract Liver-specific magnetic resonance (MR) contrast agents are increasingly used in evaluation of the liver. They are effective in detection and morphological characterization of lesions, and can be useful for evaluation of biliary tree anatomy and liver function. The typical appearances and imaging pitfalls of various tumours at MR imaging performed with these agents can be understood by the interplay of pharmacokinetics of these contrast agents and transporter expression of the tumour. This review focuses on the applications of these agents in oncological imaging. PMID:24434892

  20. Motion corrected photoacoustic difference imaging of fluorescent contrast agents

    NASA Astrophysics Data System (ADS)

    Märk, Julia; Wagener, Asja; Pönick, Sarah; Grötzinger, Carsten; Zhang, Edward; Laufer, Jan

    2016-03-01

    In fluorophores, such as exogenous dyes and genetically expressed proteins, the excited state lifetime can be modulated using pump-probe excitation at wavelengths corresponding to the absorption and fluorescence spectra. Simultaneous pump-probe pulses induce stimulated emission (SE) which, in turn, modulates the thermalized energy, and hence the photoacoustic (PA) signal amplitude. For time-delayed pulses, by contrast, SE is suppressed. Since this is not observed in endogenous chromophores, the location of the fluorophore can be determined by subtracting images acquired using simultaneous and time-delayed pump-probe excitation. This simple experimental approach exploits a fluorophorespecific contrast mechanism, and has the potential to enable deep-tissue molecular imaging at fluences below the MPE. In this study, some of the challenges to its in vivo implementation are addressed. First, the PA signal amplitude generated in fluorophores in vivo is often much smaller than that in blood. Second, tissue motion can give rise to artifacts that correspond to endogenous chromophores in the difference image. This would not allow the unambiguous detection of fluorophores. A method to suppress motion artifacts based on fast switching between simultaneous and time-delayed pump-probe excitation was developed. This enables the acquisition of PA signals using the two excitation modes with minimal time delay (20 ms), thus minimizing the effects of tissue motion. The feasibility of this method is demonstrated by visualizing a fluorophore (Atto680) in tissue phantoms, which were moved during the image acquisition to mimic tissue motion.

  1. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    NASA Astrophysics Data System (ADS)

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G.-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-06-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence.

  2. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging

    PubMed Central

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J.; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T. C.; Kim, Ki Hean

    2016-01-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence. PMID:27283889

  3. Moxifloxacin: Clinically compatible contrast agent for multiphoton imaging.

    PubMed

    Wang, Taejun; Jang, Won Hyuk; Lee, Seunghun; Yoon, Calvin J; Lee, Jun Ho; Kim, Bumju; Hwang, Sekyu; Hong, Chun-Pyo; Yoon, Yeoreum; Lee, Gilgu; Le, Viet-Hoan; Bok, Seoyeon; Ahn, G-One; Lee, Jaewook; Gho, Yong Song; Chung, Euiheon; Kim, Sungjee; Jang, Myoung Ho; Myung, Seung-Jae; Kim, Myoung Joon; So, Peter T C; Kim, Ki Hean

    2016-01-01

    Multiphoton microscopy (MPM) is a nonlinear fluorescence microscopic technique widely used for cellular imaging of thick tissues and live animals in biological studies. However, MPM application to human tissues is limited by weak endogenous fluorescence in tissue and cytotoxicity of exogenous probes. Herein, we describe the applications of moxifloxacin, an FDA-approved antibiotic, as a cell-labeling agent for MPM. Moxifloxacin has bright intrinsic multiphoton fluorescence, good tissue penetration and high intracellular concentration. MPM with moxifloxacin was demonstrated in various cell lines, and animal tissues of cornea, skin, small intestine and bladder. Clinical application is promising since imaging based on moxifloxacin labeling could be 10 times faster than imaging based on endogenous fluorescence. PMID:27283889

  4. Tailored Near-Infrared Contrast Agents for Image Guided Surgery

    PubMed Central

    Njiojob, Costyl N.; Owens, Eric A.; Narayana, Lakshminarayana; Hyun, Hoon; Choi, Hak Soo; Henary, Maged

    2015-01-01

    The success of near-infrared (NIR) fluorescence to be employed for intraoperative imaging relies on the ability to develop a highly stable, NIR fluorescent, nontoxic, biocompatible, and highly excreted compound that retains a reactive functionality for conjugation to a cancer-recognizing peptide. Herein, systematic modifications to previously detailed fluorophore ZW800-1 are explored. Specific modifications, including the isosteric replacement of the O atom of ZW800-1, include nucleophilic amine and sulfur species attached to the heptamethine core. These novel compounds have shown similar satisfactory results in biodistribution and clearance while also expressing increased stability in serum. Most importantly, all of the synthesized and evaluated compounds display a reactive functionality (either a free amino group or carboxylic acid moiety) for further bioconjugation. The results obtained from the newly prepared derivatives demonstrate that the central substitution with the studied linking agents retains the ultralow background in vivo performance of the fluorophores regardless of the total net charge. PMID:25711712

  5. Contrasting actions of pressor agents in severe autonomic failure

    NASA Technical Reports Server (NTRS)

    Jordan, J.; Shannon, J. R.; Biaggioni, I.; Norman, R.; Black, B. K.; Robertson, D.

    1998-01-01

    BACKGROUND: Orthostatic hypotension is the most disabling symptom of autonomic failure. The choice of a pressor agent is largely empiric, and it would be of great value to define predictors of a response. PATIENTS AND METHODS: In 35 patients with severe orthostatic hypotension due to multiple system atrophy or pure autonomic failure, we determined the effect on seated systolic blood pressure (SBP) of placebo, phenylpropanolamine (12.5 mg and 25 mg), yohimbine (5.4 mg), indomethacin (50 mg), ibuprofen (600 mg), caffeine (250 mg), and methylphenidate (5 mg). In a subgroup of patients, we compared the pressor effect of midodrine (5 mg) with the effect of phenylpropanolamine (12.5 mg). RESULTS: There were no significant differences in the pressor responses between patients with multiple system atrophy or pure autonomic failure. When compared with placebo, the pressor response was significant for phenylpropanolamine, yohimbine, and indomethacin. In a subgroup of patients, we confirmed that this pressor effect of phenylpropanolamine, yohimbine, and indomethacin corresponded to a significant increase in standing SBP. The pressor responses to ibuprofen, caffeine, and methylphenidate were not significantly different from placebo. Phenylpropanolamine and midodrine elicited similar pressor responses. There were no significant associations between drug response and autonomic function testing, postprandial hypotension, or plasma catecholamine levels. CONCLUSIONS: We conclude that significant increases in systolic blood pressure can be obtained in patients with orthostatic hypotension due to primary autonomic failure with phenylpropanolamine in low doses or yohimbine or indomethacin in moderate doses. The response to a pressor agent cannot be predicted by autonomic function testing or plasma catecholamines. Therefore, empiric testing with a sequence of medications, based on the risk of side effects in the individual patient and the probability of a response, is a useful approach.

  6. Pre-existing oral contrast from lanthanum carbonate: a confounding factor in CT mesenteric angiography

    PubMed Central

    Bull, M D; Shrimanker, R; Thomas, M R M; Mulgrew, C J

    2012-01-01

    A 69-year-old male was referred from the renal unit to radiology for investigation of bleeding per rectum. A CT mesenteric angiogram was performed. However, it was noted on the pre-contrast images that the large bowel contained positive oral contrast media. The procedure was abandoned as it would have been difficult to see extravasation of intravenous contrast from a bleeding point in the large bowel. The initial belief was that either the patient had been given oral contrast by ward staff on the assumption that it would be needed, or had had a recent radiological study requiring contrast, which was still present. Neither was the case; it emerged that the patient was taking Fosrenol (Shire Pharmaceuticals, Wayne, PA), a lanthanum carbonate medication used in the treatment of hyperphosphataemia. Lanthanum is densely radio-opaque and appears as positive bowel contrast on CT and plain radiography studies. When considering radiological studies specifically requiring the absence of oral contrast, it is important to be aware of the patient's drug history to avoid non-diagnostic scans with the associated radiation exposure. PMID:22457410

  7. Superparamagnetic And Paramagnetic MRI Contrast Agents: Application Of Rapid Magnetic Resonance Imaging To Assess Renal Function

    NASA Astrophysics Data System (ADS)

    Carvlin, Mark J.; Renshaw, Perry F.; Arger, Peter; Kundel, Harold L.; Dougherty, Larry; Axel, Leon; Kassab, Eleanor; Moore, Bethanne

    1988-06-01

    The paramagnetic chelate complex, gadolinium-diethylene-triamine-pentaacetic acid, Gd-DTPA, and superparamagnetic particles, such as those composed of dextran coated magnetite, function as magnetic resonance contrast agents by changing the relaxation rates, 1/T1 and 1/T2. The effects that these agents have upon MR signal intensity are determined by: the inherent biophysical properties of the tissue being imaged, the concentration of the contrast agent and the data acquisition scheme (pulse sequence parameters) employed. Following the time course of MR signal change in the first minutes after the injection of contrast agent(s) allows a dynamic assessment of organ functions in a manner analogous to certain nuclear medicine studies. In order to study renal function, sequential MR fast scan images, gradient echo (TR=35/TE=7 msec, flip angle=25 degrees), were acquired, one every 12 seconds, after intravenous injection of Gd-DTPA and/or dextran-magnetite. Gd-DTPA, which is freely filtered at the glomerulus and is neither secreted nor reabsorbed, provides information concerning renal perfusion, glomerular filtration and tubular concentrating ability. Dextran-magnetite (200 A diameter), which is primarily contained within the intravascular space shortly after injection, provides information on blood flow to and distribution within the kidney. The MR signal change observed after administration of contrast agents varied dramatically depending upon the agents injected and the imaging parameters used. Hence a broad range of physiolgic processes may be described using these techniques, i.e. contrast agent enhanced functional MR examinations.

  8. Evaluation of different small bowel contrast agents by multi - detector row CT

    PubMed Central

    Wang, Yong-Ren; Yu, Xiao-Li; Peng, Zhi-Yi

    2015-01-01

    Objective: This study aims to evaluate the effects of different oral small bowel contrast agents towards the intestinal dilatation and intestinal wall structure exhibition by the abdominal multi - detector row CT (MDCT) examination. Methods: 80 patients were performed the whole abdominal CT examination, then randomly divided into four groups, with 20 patients in each group. 45 minutes before the CT examination, the patients were served with a total of 1800 ml pure water, pure milk, dilute lactulose solution and isotonic mannitol solution, respectively. Results: The images were blinded read by two experienced abdominal radiologists in the workstation, the cross-sectional diameters of duodenum, jejunum, proximal and terminal ends of ileum of each patient were measured, then the analysis of variance was performed to analyze the differences in the intestinal dilatation among the experimental groups. The scoring method was used to score the intestinal dilatation and intestinal structure exhibition. The diluted lactulose solution and 2.5% mannitol exhibited the best intestinal dilation degrees. Similarly, the diluted lactulose solution and 2.5% mannitol exhibited the highest scores in the entire small bowel dilatation degree and intestinal structure exhibition. Conclusions: 2.5% osmotic mannitol and the diluted lactulose solution enabled the full dilatation of small bowel, and could clearly exhibit the wall structure. PMID:26629131

  9. Design Principles of Nanoparticles as Contrast Agents for Magnetic Resonance Imaging

    NASA Astrophysics Data System (ADS)

    Shan, Liang; Gu, Xinbin; Wang, Paul

    2013-09-01

    Molecular imaging is an emerging field that introduces molecular agents into traditional imaging techniques, enabling visualization, characterization and measurement of biological processes at the molecular and cellular levels in humans and other living systems. The promise of molecular imaging lies in its potential for selective potency by targeting biomarkers or molecular targets and the imaging agents serve as reporters for the selectivity of targeting. Development of an efficient molecular imaging agent depends on well-controlled high-quality experiment design involving target selection, agent synthesis, in vitro characterization, and in vivo animal characterization before it is applied in humans. According to the analysis from the Molecular Imaging and Contrast Agent Database (MICAD, ), more than 6000 molecular imaging agents with sufficient preclinical evaluation have been reported to date in the literature and this number increases by 250-300 novel agents each year. The majority of these agents are radionuclides, which are developed for positron emission tomography (PET) and single photon emission computed tomography (SPECT). Contrast agents for magnetic resonance imaging (MRI) account for only a small part. This is largely due to the fact that MRI is currently not a fully quantitative imaging technique and is less sensitive than PET and SPECT. However, because of the superior ability to simultaneously extract molecular and anatomic information, molecular MRI is attracting significant interest and various targeted nanoparticle contrast agents have been synthesized for MRI. The first and one of the most critical steps in developing a targeted nanoparticle contrast agent is target selection, which plays the central role and forms the basis for success of molecular imaging. This chapter discusses the design principles of targeted contrast agents in the emerging frontiers of molecular MRI.

  10. Modified polysaccharides as potential (19)F magnetic resonance contrast agents.

    PubMed

    Krawczyk, Tomasz; Minoshima, Masafumi; Sugihara, Fuminori; Kikuchi, Kazuya

    2016-06-16

    The introduction of 3-aminobenzotrifluoride into partially oxidized alginic acid, dextran, and polygalacturonic acid (10-100 kDa) by means of the imine formation and a subsequent reduction resulted in water-soluble materials containing 1-14% of fluorine. They showed a single or split (19)F NMR signal in a narrow range of -63 to -63.5 ppm. The observed T1 and T2 were approximately 1 and 0.2 s at 400 or 500 MHz instruments, respectively. The samples showed low toxicity and uptake toward the HeLa cells similar to native polysaccharides and were preferentially localized in lysosomes. A tail intravenous injection of 5 mg of modified dextran containing 1% of fluorine revealed that the probe was not trapped in liver, spleen or kidneys, but was quickly cleared with urine. The proposed materials can be used for imaging of the gastrointestinal tract or the genitourinary system and act as a material for more complex (19)F MRI agent synthesis. PMID:27148998

  11. Nanoparticles in magnetic resonance imaging: from simple to dual contrast agents

    PubMed Central

    Estelrich, Joan; Sánchez-Martín, María Jesús; Busquets, Maria Antònia

    2015-01-01

    Magnetic resonance imaging (MRI) has become one of the most widely used and powerful tools for noninvasive clinical diagnosis owing to its high degree of soft tissue contrast, spatial resolution, and depth of penetration. MRI signal intensity is related to the relaxation times (T1, spin–lattice relaxation and T2, spin–spin relaxation) of in vivo water protons. To increase contrast, various inorganic nanoparticles and complexes (the so-called contrast agents) are administered prior to the scanning. Shortening T1 and T2 increases the corresponding relaxation rates, 1/T1 and 1/T2, producing hyperintense and hypointense signals respectively in shorter times. Moreover, the signal-to-noise ratio can be improved with the acquisition of a large number of measurements. The contrast agents used are generally based on either iron oxide nanoparticles or ferrites, providing negative contrast in T2-weighted images; or complexes of lanthanide metals (mostly containing gadolinium ions), providing positive contrast in T1-weighted images. Recently, lanthanide complexes have been immobilized in nanostructured materials in order to develop a new class of contrast agents with functions including blood-pool and organ (or tumor) targeting. Meanwhile, to overcome the limitations of individual imaging modalities, multimodal imaging techniques have been developed. An important challenge is to design all-in-one contrast agents that can be detected by multimodal techniques. Magnetoliposomes are efficient multimodal contrast agents. They can simultaneously bear both kinds of contrast and can, furthermore, incorporate targeting ligands and chains of polyethylene glycol to enhance the accumulation of nanoparticles at the site of interest and the bioavailability, respectively. Here, we review the most important characteristics of the nanoparticles or complexes used as MRI contrast agents. PMID:25834422

  12. Breakthrough reactions of iodinated and gadolinium contrast media after oral steroid premedication protocol

    PubMed Central

    2014-01-01

    Background Adverse reactions to iodinated and gadolinium contrast media are an important clinical issue. Although some guidelines have proposed oral steroid premedication protocols to prevent adverse reactions, some patients may have reactions to contrast media in spite of premedication (breakthrough reaction; BTR). The purpose of this study was to assess the frequency, type and severity of BTR when following an oral steroid premedication protocol. Methods All iodinated and gadolinium contrast-enhanced radiologic examinations between August 2011 and February 2013 for which the premedication protocol was applied in our institution were assessed for BTRs. Results The protocol was applied to a total of 252 examinations (153 patients, ages 15–87 years; 63 males, 90 females). Of these, 152 were for prior acute adverse reactions to contrast media, 85 were for a history of bronchial asthma, and 15 were for other reasons. There were 198 contrast enhanced CTs and 54 contrast enhanced MRIs. There were nine BTR (4.5%) for iodinated contrast media, and only one BTR (1.9%) for gadolinium contrast media: eight were mild and one was moderate. No patient who had a mild index reaction (IR) had a severe BTR. Conclusion Incidence of BTRs when following the premedication protocol was low. This study by no means proves the efficacy of premedication, but provides some support for following a premedication protocol to improve safety of contrast-enhanced examinations when prior adverse reactions are mild, or when there is a history of asthma. PMID:25287952

  13. Acoustic responses of monodisperse lipid-encapsulated microbubble contrast agents produced by flow focusing

    PubMed Central

    Kaya, Mehmet; Feingold, Steven; Hettiarachchi, Kanaka; Lee, Abraham P; Dayton, Paul A

    2010-01-01

    Lipid-encapsulated microbubbles are used as contrast agents in ultrasound imaging. Currently available commercially made contrast agents have a polydisperse size distribution. It has been hypothesised that improved imaging sensitivity could be achieved with a uniform microbubble radius. We have recently developed microfluidics technology to produce contrast agents with a nearly monodisperse distribution. In this manuscript, we analyze echo responses from individual microbubbles from monodisperse populations in order to establish the relationship between scattered echo, microbubble radius, and excitation frequency. Simulations of bubble response from a modified Rayleigh-Plesset type model corroborate experimental data. Results indicate that microbubble echo response can be greatly increased by optimal combinations of microbubble radius and acoustic excitation frequency. These results may have a significant impact in the formulation of contrast agents to improve ultrasonic sensitivity. PMID:21475641

  14. Synthesis and characterization of ethosomal contrast agents containing iodine for computed tomography (CT) imaging applications.

    PubMed

    Shin, Hanjin; Cho, Young-Min; Lee, Kangtaek; Lee, Chang-Ha; Choi, Byoung Wook; Kim, Bumsang

    2014-06-01

    As a first step in the development of novel liver-specific contrast agents using ethosomes for computed tomography (CT) imaging applications, we entrapped iodine within ethosomes, which are phospholipid vesicular carriers containing relatively high alcohol concentrations, synthesized using several types of alcohol, such as methanol, ethanol, and propanol. The iodine containing ethosomes that were prepared using methanol showed the smallest vesicle size (392 nm) and the highest CT density (1107 HU). The incorporation of cholesterol into the ethosomal contrast agents improved the stability of the ethosomes but made the vesicle size large. The ethosomal contrast agents were taken up well by macrophage cells and showed no cellular toxicity. The results demonstrated that ethosomes containing iodine, as prepared in this study, have potential as contrast agents for applications in CT imaging. PMID:24188576

  15. The evolution of gadolinium based contrast agents: from single-modality to multi-modality.

    PubMed

    Zhang, Li; Liu, Ruiqing; Peng, Hui; Li, Penghui; Xu, Zushun; Whittaker, Andrew K

    2016-05-19

    Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications. PMID:27159645

  16. The evolution of gadolinium based contrast agents: from single-modality to multi-modality

    NASA Astrophysics Data System (ADS)

    Zhang, Li; Liu, Ruiqing; Peng, Hui; Li, Penghui; Xu, Zushun; Whittaker, Andrew K.

    2016-05-01

    Gadolinium-based contrast agents are extensively used as magnetic resonance imaging (MRI) contrast agents due to their outstanding signal enhancement and ease of chemical modification. However, it is increasingly recognized that information obtained from single modal molecular imaging cannot satisfy the higher requirements on the efficiency and accuracy for clinical diagnosis and medical research, due to its limitation and default rooted in single molecular imaging technique itself. To compensate for the deficiencies of single function magnetic resonance imaging contrast agents, the combination of multi-modality imaging has turned to be the research hotpot in recent years. This review presents an overview on the recent developments of the functionalization of gadolinium-based contrast agents, and their application in biomedicine applications.

  17. Dynamic manipulation of magnetic contrast agents in photoacoustic imaging

    NASA Astrophysics Data System (ADS)

    Jia, Congxian; Xia, Jinjun; Pelivanov, Ivan M.; Seo, Chi Hyung; Hu, Xiaoge; Jin, Yongdong; Gao, Xiaohu; O'Donnell, Matthew

    2011-03-01

    Magnetic nanoparticles (MNPs) have been used extensively ex vivo for cellular and molecular separations. We recently showed that a coupled nanoparticle combining a superparamagnetic core with a thin, isolated gold shell providing strong absorption in the near infrared can be used for magnetomotive photoacoustic imaging (mmPA), a new technique in which magnetic manipulation of the particle during PA imaging greatly enhances molecular contrast specificity. This particle can also be biologically targeted for in vivo applications, where mmPA imaging provides a spatially localized readout of magnetic manipulations. As an initial test of potential in vivo molecular assays and integrated molecular therapeutics using magnetic manipulation of nanoparticles, we present experiments demonstrating PA readout of trapped magnetic particles in a flow field. An aqueous solution containing a concentration of 0.05-mg/ml 10-μM superparamagnetic iron oxide particles flowed in a 1.65-mm diameter Zeus PTFE (Teflon) sublite wall tubing at three velocities of 0.8, 1.5 and 3.0-mm/s. Opposed permanent magnets separated by 40-mm were positioned on both sides of the tube. As expected, the targeted objects can be magnetically captured and accumulated locally. By translating the magnets, a dynamic magnetic field (0.1-0.3-T) was alternately generated on the side of the tube closest to one of the magnets and created a synchronous PA motion from accumulated targeted objects. This synchronized motion can be used to differentiate the stationary background or other PA sources moving asynchronously with magnetic manipulations (e.g., moving blood) from targeted cells moving synchronously with the magnetic field. This technology can potentially provide sensitive molecular assays of cellular targets travelling in the vasculature (e.g., metastatic tumor cells).

  18. Acoustic radiation pressure: A 'phase contrast' agent for x-ray phase contrast imaging

    SciTech Connect

    Bailat, Claude J.; Hamilton, Theron J.; Rose-Petruck, Christoph; Diebold, Gerald J.

    2004-11-08

    We show that the radiation pressure exerted by a beam of ultrasound can be used for contrast enhancement in high-resolution x-ray imaging of tissue and soft materials. Interfacial features of objects are highlighted as a result of both the displacement introduced by the ultrasound and the inherent sensitivity of x-ray phase contrast imaging to density variations. The potential of the method is demonstrated by imaging microscopic tumor phantoms embedded into tissue with a thickness typically presented in mammography. The detection limit of micrometer size masses exceeds the resolution of currently available mammography imaging systems. The directionality of the acoustic radiation force and its localization in space permits the imaging of ultrasound-selected tissue volumes. The results presented here suggest that the method may permit the detection of tumors in soft tissue in their early stage of development.

  19. Submicron polycaprolactone particles as a carrier for imaging contrast agent for in vitro applications.

    PubMed

    Iqbal, Muhammad; Robin, Sophie; Humbert, Philippe; Viennet, Céline; Agusti, Geraldine; Fessi, Hatem; Elaissari, Abdelhamid

    2015-12-01

    Fluorescent materials have recently attracted considerable attention due to their unique properties and high performance as imaging agent in biomedical fields. Different imaging agents have been encapsulated in order to restrict its delivery to a specific area. In this study, a fluorescent contrast agent was encapsulated for in vitro application by polycaprolactone (PCL) polymer. The encapsulation was performed using modified double emulsion solvent evaporation technique with sonication. Fluorescent nanoparticles (20 nm) were incorporated in the inner aqueous phase of double emulsion. A number of samples were fabricated using different concentrations of fluorescent contrast agent. The contrast agent-containing submicron particle was characterized by a zetasizer for average particle size, SEM and TEM for morphology observations and fluorescence spectrophotometer for encapsulation efficiency. Moreover, contrast agent distribution in the PCL matrix was determined by confocal microscopy. The incorporation of contrast agent in different concentrations did not affect the physicochemical properties of PCL particles and the average size of encapsulated particles was found to be in the submicron range. PMID:26454055

  20. Detection of Sulfatase Enzyme Activity with a CatalyCEST MRI Contrast Agent.

    PubMed

    Sinharay, Sanhita; Fernández-Cuervo, Gabriela; Acfalle, Jasmine P; Pagel, Mark D

    2016-05-01

    A chemical exchange saturation transfer (CEST) MRI contrast agent has been developed that detects sulfatase enzyme activity. The agent produces a CEST signal at δ=5.0 ppm before enzyme activity, and a second CEST signal appears at δ=9.0 ppm after the enzyme cleaves a sulfate group from the agent. The comparison of the two signals improved detection of sulfatase activity. PMID:26956002

  1. Evaluation of microbubble contrast agents for dynamic imaging with x-ray phase contrast

    PubMed Central

    Millard, T. P.; Endrizzi, M.; Everdell, N.; Rigon, L.; Arfelli, F.; Menk, R. H.; Stride, E.; Olivo, A.

    2015-01-01

    X-rays are commonly used as a means to image the inside of objects opaque to visible light, as their short wavelength allows penetration through matter and the formation of high spatial resolution images. This physical effect has found particular importance in medicine where x-ray based imaging is routinely used as a diagnostic tool. Increasingly, however, imaging modalities that provide functional as well as morphological information are required. In this study the potential to use x-ray phase based imaging as a functional modality through the use of microbubbles that can be targeted to specific biological processes is explored. We show that the concentration of a microbubble suspension can be monitored quantitatively whilst in flow using x-ray phase contrast imaging. This could provide the basis for a dynamic imaging technique that combines the tissue penetration, spatial resolution, and high contrast of x-ray phase based imaging with the functional information offered by targeted imaging modalities. PMID:26219661

  2. Potential of high-Z contrast agents in clinical contrast-enhanced computed tomography

    SciTech Connect

    Nowak, Tristan; Hupfer, Martin; Brauweiler, Robert; Eisa, Fabian; Kalender, Willi A.

    2011-12-15

    Purpose: Currently, only iodine- and barium-based contrast media (CM) are used in clinical contrast-enhanced computed tomography (CE-CT). High-Z metals would produce a higher contrast at equal mass density for the x-ray spectra used in clinical CT. Using such materials might allow for significant dose reductions in CE-CT. The purpose of this study was to quantify the potential for dose reduction when using CM based on heavy metals. Methods: The contrast-to-noise ratio weighted by dose (CNRD) was determined as a function of scan protocol by means of measurements and simulations on a clinical CT scanner. For simulations, water cylinders with diameters 160, 320, 480, and 640 mm were used to cover a broad range of patient sizes. Measurements were conducted with 160 and 320 mm water-equivalent plastic cylinders. A central bore of 13 mm diameter was present in all phantoms. The tube voltage was varied from 80 to 140 kV for measurements and from 60 to 180 kV for simulations. Additional tin filtration of thicknesses 0.4, 0.8, and 1.2 mm was applied in the simulation to evaluate a range of spectral hardness. The bore was filled with a mixture of water and 10 mg/ml of pure iodine, holmium, gadolinium, ytterbium, osmium, tungsten, gold, and bismuth for the simulations and with aqueous solutions of ytterbium, tungsten, gold, and bismuth salts as well as Iopromid containing 10 mg/ml of the pure materials for the measurements. CNRDs were compared to iodine at phantom size-dependent reference voltages for all high-Z materials and the resulting dose reduction was calculated for equal contrast-to-noise ratio. Results: Dose reduction potentials strongly depended on phantom size, spectral hardness, and tube voltage. Depending on the added filtration, a dose reduction of 19%-60% could be reached at 80 kV with gadolinium for the 160 mm phantom, 52%-69% at 100 kV with holmium for the 320 mm phantom, 62%-78% with 120 kV for hafnium and the 480 mm phantom and 74%-86% with 140 kV for gold

  3. A liposomal Gd contrast agent does not cross the mouse placental barrier.

    PubMed

    Shetty, Anil N; Pautler, Robia; Ghagahda, Ketan; Rendon, David; Gao, Haijun; Starosolski, Zbigniew; Bhavane, Rohan; Patel, Chandreshkumar; Annapragada, Ananth; Yallampalli, Chandrasekhar; Lee, Wesley

    2016-01-01

    The trans-placental permeability of liposomal Gadolinium (Gd) nanoparticle contrast agents was evaluated in a pregnant mouse model. Pregnant Balb/c mice at 16.5 (±1) days of gestation were imaged using a 3D Spoiled Gradient Echo method at 9.4 T using two contrast agents: a clinically approved Gd chelate, Multihance(®) (gadobenate dimeglumine), and a novel experimental liposomal Gd agent. A Dynamic Contrast Enhancement (DCE) protocol was used to capture the dynamics of contrast entry and distribution in the placenta, and clearance from circulation. A blinded clinical radiologist evaluated both sets of images. A reference region model was used to measure the placental flow and physiological parameters; volume transfer constant (K(trans)), efflux rate constant (K(ep)). The Gd content of excised placentae and fetuses was measured, using inductively coupled plasma mass spectrometry (ICP-MS). MRI images of pregnant mice and ICP-MS analyses of placental and fetal tissue demonstrated undetectably low transplacental permeation of the liposomal Gd agent, while the clinical agent (Multihance) avidly permeated the placental barrier. Image interpretation and diagnostic quality was equivalent between the two contrast agents. Additional testing to determine both maternal and fetal safety of liposomal Gd is suggested. PMID:27298076

  4. A liposomal Gd contrast agent does not cross the mouse placental barrier

    PubMed Central

    Shetty, Anil N.; Pautler, Robia; Ghagahda, Ketan; Rendon, David; Gao, Haijun; Starosolski, Zbigniew; Bhavane, Rohan; Patel, Chandreshkumar; Annapragada, Ananth; Yallampalli, Chandrasekhar; Lee, Wesley

    2016-01-01

    The trans-placental permeability of liposomal Gadolinium (Gd) nanoparticle contrast agents was evaluated in a pregnant mouse model. Pregnant Balb/c mice at 16.5 (±1) days of gestation were imaged using a 3D Spoiled Gradient Echo method at 9.4 T using two contrast agents: a clinically approved Gd chelate, Multihance® (gadobenate dimeglumine), and a novel experimental liposomal Gd agent. A Dynamic Contrast Enhancement (DCE) protocol was used to capture the dynamics of contrast entry and distribution in the placenta, and clearance from circulation. A blinded clinical radiologist evaluated both sets of images. A reference region model was used to measure the placental flow and physiological parameters; volume transfer constant (Ktrans), efflux rate constant (Kep). The Gd content of excised placentae and fetuses was measured, using inductively coupled plasma mass spectrometry (ICP-MS). MRI images of pregnant mice and ICP-MS analyses of placental and fetal tissue demonstrated undetectably low transplacental permeation of the liposomal Gd agent, while the clinical agent (Multihance) avidly permeated the placental barrier. Image interpretation and diagnostic quality was equivalent between the two contrast agents. Additional testing to determine both maternal and fetal safety of liposomal Gd is suggested. PMID:27298076

  5. Quantitative imaging of cell-permeable magnetic resonance contrast agents using x-ray fluorescence.

    PubMed

    Endres, Paul J; Macrenaris, Keith W; Vogt, Stefan; Allen, Matthew J; Meade, Thomas J

    2006-01-01

    The inability to transduce cellular membranes is a limitation of current magnetic resonance imaging probes used in biologic and clinical settings. This constraint confines contrast agents to extracellular and vascular regions of the body, drastically reducing their viability for investigating processes and cycles in developmental biology. Conversely, a contrast agent with the ability to permeate cell membranes could be used in visualizing cell patterning, cell fate mapping, gene therapy, and, eventually, noninvasive cancer diagnosis. Therefore, we describe the synthesis and quantitative imaging of four contrast agents with the capability to cross cell membranes in sufficient quantity for detection. Each agent is based on the conjugation of a Gd(III) chelator with a cellular transduction moiety. Specifically, we coupled Gd(III)-diethylenetriaminepentaacetic acid DTPA and Gd(III)-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid with an 8-amino acid polyarginine oligomer and an amphipathic stilbene molecule, 4-amino-4'-(N,N-dimethylamino)stilbene. The imaging modality that provided the best sensitivity and spatial resolution for direct detection of the contrast agents is synchrotron radiation x-ray fluorescence (SR-XRF). Unlike optical microscopy, SR-XRF provides two-dimensional images with resolution 10(3) better than (153)Gd gamma counting, without altering the agent by organic fluorophore conjugation. The transduction efficiency of the intracellular agents was evaluated by T(1) analysis and inductively coupled plasma mass spectrometry to determine the efficacy of each chelate-transporter combination. PMID:17150161

  6. Optimal Contrast Agent Staining of Ligaments and Tendons for X-Ray Computed Tomography.

    PubMed

    Balint, Richard; Lowe, Tristan; Shearer, Tom

    2016-01-01

    X-ray computed tomography has become an important tool for studying the microstructures of biological soft tissues, such as ligaments and tendons. Due to the low X-ray attenuation of such tissues, chemical contrast agents are often necessary to enhance contrast during scanning. In this article, the effects of using three different contrast agents-iodine potassium iodide solution, phosphotungstic acid and phosphomolybdic acid-are evaluated and compared. Porcine anterior cruciate ligaments, patellar tendons, medial collateral ligaments and lateral collateral ligaments were used as the basis of the study. Three samples of each of the four ligament/tendon types were each assigned a different contrast agent (giving a total of twelve samples), and the progression of that agent through the tissue was monitored by performing a scan every day for a total period of five days (giving a total of sixty scans). Since the samples were unstained on day one, they had been stained for a total of four days by the time of the final scans. The relative contrast enhancement and tissue deformation were measured. It was observed that the iodine potassium iodide solution penetrated the samples fastest and caused the least sample shrinkage on average (although significant deformation was observed by the time of the final scans), whereas the phosphomolybdic acid caused the greatest sample shrinkage. Equations describing the observed behaviour of the contrast agents, which can be used to predict optimal staining times for ligament and tendon X-ray computed tomography, are presented. PMID:27078030

  7. Laser-induced photoacoustic tomography enhanced with an optical contrast agent

    NASA Astrophysics Data System (ADS)

    Wang, Xueding; Ku, Geng; Xie, Xueyi; Wegiel, Malgorzata A.; Bornhop, Darryl J.; Stoica, George; Wang, Lihong V.

    2004-07-01

    Optical contrast agents, such as indocyanine dyes, nano-particles and their functional derivatives, have been widely applied to enhance the sensitivity and specificity of optical imaging. However, due to the overwhelming scattering of light in biological tissues, the spatial resolution of traditional optical imaging degrades drastically as the imaging depth increases. For the first time to our knowledge, non-invasive in vivo photoacoustic imaging of an optical contrast agent, distributed in the rat brain, was implemented with near-infrared light. Injection of indocyanine green polyethylene glycol, a contrast agent with a high absorption at the 805-nm wavelength, into the circulatory system of a rat enhanced the absorption contrast between the blood vessels and the background brain tissues. Because near-infrared light can penetrate deep into the brain tissues through the skin and skull, we were able to successfully reconstruct the vascular distribution in the rat brain from the detected photoacoustic signals. The dynamic concentration of this contrast agent in the brain blood after the intravenous injection was also studied. This work proved that the distribution of an exogenous contrast agent in biological tissues can be imaged clearly and accurately by photoacoustic tomography. This new technology has high potential for application in dynamic and molecular medical imaging.

  8. [Immediate and delayed hypersensitivity reactions to iodinated radiographic contrast agents: an update].

    PubMed

    Khachman, Dalia; Gandia, Peggy; Sallerin, François; Mailly, Nicolas

    2009-01-01

    Diagnostic and interventional radiology of patients is nowadays crucial with increasing requirement for iodinated contrast agents infusion. Besides adverse reactions after administration of the iodinated contrast agents due to their toxicity, immediate hypersensitivity reactions and reactions resembling delayed hypersensitivity appearing from 1 hour to several days later, have been reported. Patients at high risk to develop such adverse events have to be detected on the basis of their risk factors in order to prevent or limit serious outcomes. Previous reactions to contrast media, asthma, atopy and cardiovascular disorders are risk factors for anaphylactic or anaphylactoid reactions. Female gender, age and beta-blockers increase the severity. This article aims to summarize the risk of allergic reactions related to the use of iodinated contrast agents and to suggest a way for diagnosis, treatment and prevention according to each clinical situation. PMID:19863909

  9. Structural and functional photoacoustic molecular tomography aided by emerging contrast agents

    PubMed Central

    Nie, Liming

    2015-01-01

    Photoacoustic tomography (PAT) can offer structural, functional and molecular contrasts at scalable observation level. By ultrasonically overcoming the strong optical scattering, this imaging technology can reach centimeters penetration depth while retaining high spatial resolution in biological tissue. Recent extensive research has been focused on developing new contrast agents to improve the imaging sensitivity, specificity and efficiency. These emerging materials have substantially accelerated PAT applications in signal sensing, functional imaging, biomarker labeling and therapy monitoring etc. Here, the potentials of different optical probes as PAT contrast agents were elucidated. We first describe the instrumental embodiments and the measured functional parameters, then focus on emerging contrast agent-based PAT applications, and finally discuss the challenges and prospects. PMID:24967718

  10. High-Relaxivity MRI Contrast Agents: Where Coordination Chemistry Meets Medical Imaging

    SciTech Connect

    Werner, Eric J.; Datta, Ankona; Jocher, Christoph J.; Raymond, Kenneth N.

    2008-01-15

    The desire to improve and expand the scope of clinical magnetic resonance imaging (MRI) has prompted the search for contrast agents of higher efficiency. The development of better agents requires consideration of the fundamental coordination chemistry of the gadolinium(III) ion and the parameters that affect its efficacy as a proton relaxation agent. In optimizing each parameter, other practical issues such as solubility and in vivo toxicity must also be addressed, making the attainment of safe, high-relaxivity agents a challenging goal. Here we present recent advances in the field, with an emphasis on the hydroxypyridinone family of Gd{sup III} chelates.

  11. Effect of gas-containing microspheres and echo contrast agents on free radical formation by ultrasound.

    PubMed

    Kondo, T; Misík, V; Riesz, P

    1998-09-01

    Stabilized microbubbles (microspheres) are widely used to enhance the contrast of ultrasound imaging. Our data provide direct evidence that the contrast agents, Levovist, PVC-AN (polyvinylidene chloride-acrylonitryl copolymer), and Albunex (compared to 5% human albumin), at concentrations comparable to those used for ultrasound imaging, enhance H2O2 production (through the superoxide-dependent pathway) in air-saturated aqueous solutions exposed to 47 kHz ultrasound above the cavitation threshold. These agents also act as scavengers of .H atoms and .OH radicals, thus lowering H2O2 formation (by recombination of .OH radicals) in argon-saturated solutions. EPR spin trapping also reveals that secondary radicals derived from the contrast agents are produced by reactions with .H and .OH which are formed by pyrolysis of water inside cavitation bubbles. In addition, the contrast agents themselves undergo pyrolysis reactions in the cavitation bubbles as demonstrated by formation of methyl radicals. Possible deleterious consequences of the formation of sonochemical intermediates may have to be assessed, particularly since some of the echo contrast agents have been shown to lower the cavitation threshold of diagnostic ultrasound. Unlike the microspheres formed from organic molecules, inorganic microspheres, Eccospheres, because of their stability and inert nature with respect to participation in free radical processes, appear to be suitable tools for enhancing the yields of aqueous sonochemical reactions. PMID:9741598

  12. Main applications of hybrid PET-MRI contrast agents: a review.

    PubMed

    Kiani, A; Esquevin, A; Lepareur, N; Bourguet, P; Le Jeune, F; Gauvrit, Jy

    2016-03-01

    In medical imaging, the continuous quest to improve diagnostic performance and optimize treatment strategies has led to the use of combined imaging modalities. Positron emission tomography (PET) and computed tomography (CT) is a hybrid imaging existing already for many years. The high spatial and contrast resolution of magnetic resonance imaging (MRI) and the high sensitivity and molecular information from PET imaging are leading to the development of this new hybrid imaging along with hybrid contrast agents. To create a hybrid contrast agent for PET-MRI device, a PET radiotracer needs to be combined with an MRI contrast agent. The most common approach is to add a radioactive isotope to the surface of a small superparamagnetic iron oxide (SPIO) particle. The resulting agents offer a wide range of applications, such as pH variation monitoring, non-invasive angiography and early imaging diagnosis of atherosclerosis. Oncology is the most promising field with the detection of sentinel lymph nodes and the targeting of tumor neoangiogenesis. Oncology and cardiovascular imaging are thus major areas of development for hybrid PET-MRI imaging systems and hybrid contrast agents. The aim is to combine high spatial resolution, high sensitivity, morphological and functional information. Future prospects include the use of specific antibodies and hybrid multimodal PET-MRI-ultrasound-fluorescence imaging with the potential to provide overall pre-, intra- and postoperative patient care. Copyright © 2015 John Wiley & Sons, Ltd. PMID:26632007

  13. Thermal Excitation of Gadolinium-Based Contrast Agents Using Spin Resonance

    PubMed Central

    Fridjhon, Peter; Rubin, David M.

    2016-01-01

    Theoretical and experimental investigations into the thermal excitation of liquid paramagnetic contrast agents using the spin resonance relaxation mechanism are presented. The electronic spin-lattice relaxation time τ1e of gadolinium-based contrast agents, which is estimated at 0.1 ns, is ten orders of magnitude faster than the relaxation time of protons in water. The shorter relaxation time is found to significantly increase the rate of thermal energy deposition. To the authors’ knowledge this is the first study of gadolinium based contrast agents in a liquid state used as thermal agents. Analysis shows that when τ1e and other experimental parameters are optimally selected, a maximum theoretical heating rate of 29.4 °C.s−1 could be achieved which would suffice for clinical thermal ablation of neoplasms. The experimental results show a statistically significant thermal response for two out of the four contrast agents tested. The results are compared to the simulated estimates via analysis of a detailed model of the system. While these experimentally determined temperature rises are small and thus of no clinical utility, their presence supports the theoretical analysis and strongly suggests that the chemical structure of the selected compounds plays an important role in this mechanism of heat deposition. There exists an opportunity for the development of alternative gadolinium-based compounds with an order of magnitude longer τ1e in a diluted form to be used as an efficient hyperthermia agent for clinical use. PMID:27341338

  14. Thermal Excitation of Gadolinium-Based Contrast Agents Using Spin Resonance.

    PubMed

    Dinger, Steven C; Fridjhon, Peter; Rubin, David M

    2016-01-01

    Theoretical and experimental investigations into the thermal excitation of liquid paramagnetic contrast agents using the spin resonance relaxation mechanism are presented. The electronic spin-lattice relaxation time τ1e of gadolinium-based contrast agents, which is estimated at 0.1 ns, is ten orders of magnitude faster than the relaxation time of protons in water. The shorter relaxation time is found to significantly increase the rate of thermal energy deposition. To the authors' knowledge this is the first study of gadolinium based contrast agents in a liquid state used as thermal agents. Analysis shows that when τ1e and other experimental parameters are optimally selected, a maximum theoretical heating rate of 29.4 °C.s-1 could be achieved which would suffice for clinical thermal ablation of neoplasms. The experimental results show a statistically significant thermal response for two out of the four contrast agents tested. The results are compared to the simulated estimates via analysis of a detailed model of the system. While these experimentally determined temperature rises are small and thus of no clinical utility, their presence supports the theoretical analysis and strongly suggests that the chemical structure of the selected compounds plays an important role in this mechanism of heat deposition. There exists an opportunity for the development of alternative gadolinium-based compounds with an order of magnitude longer τ1e in a diluted form to be used as an efficient hyperthermia agent for clinical use. PMID:27341338

  15. Connexin 43-targeted T1 contrast agent for MRI diagnosis of glioma.

    PubMed

    Abakumova, Tatiana; Abakumov, Maxim; Shein, Sergey; Chelushkin, Pavel; Bychkov, Dmitry; Mukhin, Vladimir; Yusubalieva, Gaukhar; Grinenko, Nadezhda; Kabanov, Alexander; Nukolova, Natalia; Chekhonin, Vladimir

    2016-01-01

    Glioblastoma multiforme is the most aggressive form of brain tumor. Early and accurate diagnosis of glioma and its borders is an important step for its successful treatment. One of the promising targets for selective visualization of glioma and its margins is connexin 43 (Cx43), which is highly expressed in reactive astrocytes and migrating glioma cells. The purpose of this study was to synthesize a Gd-based contrast agent conjugated with specific antibodies to Cx43 for efficient visualization of glioma C6 in vivo. We have prepared stable nontoxic conjugates of monoclonal antibody to Cx43 and polylysine-DTPA ligands complexed with Gd(III), which are characterized by higher T1 relaxivity (6.5 mM(-1) s(-1) at 7 T) than the commercial agent Magnevist® (3.4 mM(-1) s(-1)). Cellular uptake of Cx43-specific T1 contrast agent in glioma C6 cells was more than four times higher than the nonspecific IgG-contrast agent, as detected by flow cytometry and confocal analysis. MRI experiments showed that the obtained agents could markedly enhance visualization of glioma C6 in vivo after their intravenous administration. Significant accumulation of Cx43-targeted contrast agents in glioma and the peritumoral zone led not only to enhanced contrast but also to improved detection of the tumor periphery. Fluorescence imaging confirmed notable accumulation of Cx43-specific conjugates in the peritumoral zone compared with nonspecific IgG conjugates at 24 h after intravenous injection. All these features of Cx43-targeted contrast agents might be useful for more precise diagnosis of glioma and its borders by MRI. PMID:26265140

  16. Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent

    PubMed Central

    Kossatz, Susanne; Brand, Christian; Gutiontov, Stanley; Liu, Jonathan T. C.; Lee, Nancy Y.; Gönen, Mithat; Weber, Wolfgang A.; Reiner, Thomas

    2016-01-01

    Earlier and more accurate detection of oral squamous cell carcinoma (OSCC) is essential to improve the prognosis of patients and to reduce the morbidity of surgical therapy. Here, we demonstrate that the nuclear enzyme Poly(ADP-ribose)Polymerase 1 (PARP1) is a promising target for optical imaging of OSCC with the fluorescent dye PARPi-FL. In patient-derived OSCC specimens, PARP1 expression was increased 7.8 ± 2.6-fold when compared to normal tissue. Intravenous injection of PARPi-FL allowed for high contrast in vivo imaging of human OSCC models in mice with a surgical fluorescence stereoscope and high-resolution imaging systems. The emitted signal was specific for PARP1 expression and, most importantly, PARPi-FL can be used as a topical imaging agent, spatially resolving the orthotopic tongue tumors in vivo. Collectively, our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve as a screening tool and help to guide surgical resections. PMID:26900125

  17. Detection and delineation of oral cancer with a PARP1 targeted optical imaging agent.

    PubMed

    Kossatz, Susanne; Brand, Christian; Gutiontov, Stanley; Liu, Jonathan T C; Lee, Nancy Y; Gönen, Mithat; Weber, Wolfgang A; Reiner, Thomas

    2016-01-01

    Earlier and more accurate detection of oral squamous cell carcinoma (OSCC) is essential to improve the prognosis of patients and to reduce the morbidity of surgical therapy. Here, we demonstrate that the nuclear enzyme Poly(ADP-ribose)Polymerase 1 (PARP1) is a promising target for optical imaging of OSCC with the fluorescent dye PARPi-FL. In patient-derived OSCC specimens, PARP1 expression was increased 7.8 ± 2.6-fold when compared to normal tissue. Intravenous injection of PARPi-FL allowed for high contrast in vivo imaging of human OSCC models in mice with a surgical fluorescence stereoscope and high-resolution imaging systems. The emitted signal was specific for PARP1 expression and, most importantly, PARPi-FL can be used as a topical imaging agent, spatially resolving the orthotopic tongue tumors in vivo. Collectively, our results suggest that PARP1 imaging with PARPi-FL can enhance the detection of oral cancer, serve as a screening tool and help to guide surgical resections. PMID:26900125

  18. Poly(Lactic-co-Glycolic) Acid as a Carrier for Imaging Contrast Agents

    PubMed Central

    Doiron, Amber L.; Homan, Kimberly A.; Emelianov, Stanislav; Brannon-Peppas, Lisa

    2010-01-01

    Purpose With the broadening field of nanomedicine poised for future molecular level therapeutics, nano-and microparticles intended for the augmentation of either single- or multimodal imaging are created with PLGA as the chief constituent and carrier. Methods Emulsion techniques were used to encapsulate hydrophilic and hydrophobic imaging contrast agents in PLGA particles. The imaging contrast properties of these PLGA particles were further enhanced by reducing silver onto the PLGA surface, creating a silver cage around the polymeric core. Results The MRI contrast agent Gd-DTPA and the exogenous dye rhodamine 6G were both encapsulated in PLGA and shown to enhance MR and fluorescence contrast, respectively. The silver nanocage built around PLGA nanoparticles exhibited strong near infrared light absorbance properties, making it a suitable contrast agent for optical imaging strategies such as photoacoustic imaging. Conclusions The biodegradable polymer PLGA is an extremely versatile nano- and micro-carrier for several imaging contrast agents with the possibility of targeting diseased states at a molecular level. PMID:19034628

  19. A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI.

    PubMed

    von Zur Muhlen, Constantin; Sibson, Nicola R; Peter, Karlheinz; Campbell, Sandra J; Wilainam, Panop; Grau, Georges E; Bode, Christoph; Choudhury, Robin P; Anthony, Daniel C

    2008-03-01

    Human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. Here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with MRI, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional MRI. Ligand-induced binding sites (LIBS) on activated platelet glycoprotein IIb/IIIa receptors were detected in the brains of malaria-infected mice 6 days after inoculation with Plasmodium berghei using microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody specific for the LIBS (LIBS-MPIO). No binding of the LIBS-MPIO contrast agent was detected in uninfected animals. A combination of LIBS-MPIO MRI, confocal microscopy, and transmission electron microscopy revealed that the proinflammatory cytokine TNF-alpha, but not IL-1beta or lymphotoxin-alpha (LT-alpha), induced adherence of platelets to cerebrovascular endothelium. Peak platelet adhesion was found 12 h after TNF-alpha injection and was readily detected with LIBS-MPIO contrast-enhanced MRI. Temporal studies revealed that the level of MPIO-induced contrast was proportional to the number of platelets bound. Thus, the LIBS-MPIO contrast agent enabled noninvasive detection of otherwise undetectable cerebral pathology by in vivo MRI before the appearance of clinical disease, highlighting the potential of targeted contrast agents for diagnostic, mechanistic, and therapeutic studies. PMID:18274670

  20. Optimal Contrast Agent Staining of Ligaments and Tendons for X-Ray Computed Tomography

    PubMed Central

    Balint, Richard; Lowe, Tristan

    2016-01-01

    X-ray computed tomography has become an important tool for studying the microstructures of biological soft tissues, such as ligaments and tendons. Due to the low X-ray attenuation of such tissues, chemical contrast agents are often necessary to enhance contrast during scanning. In this article, the effects of using three different contrast agents—iodine potassium iodide solution, phosphotungstic acid and phosphomolybdic acid—are evaluated and compared. Porcine anterior cruciate ligaments, patellar tendons, medial collateral ligaments and lateral collateral ligaments were used as the basis of the study. Three samples of each of the four ligament/tendon types were each assigned a different contrast agent (giving a total of twelve samples), and the progression of that agent through the tissue was monitored by performing a scan every day for a total period of five days (giving a total of sixty scans). Since the samples were unstained on day one, they had been stained for a total of four days by the time of the final scans. The relative contrast enhancement and tissue deformation were measured. It was observed that the iodine potassium iodide solution penetrated the samples fastest and caused the least sample shrinkage on average (although significant deformation was observed by the time of the final scans), whereas the phosphomolybdic acid caused the greatest sample shrinkage. Equations describing the observed behaviour of the contrast agents, which can be used to predict optimal staining times for ligament and tendon X-ray computed tomography, are presented. PMID:27078030

  1. A contrast agent recognizing activated platelets reveals murine cerebral malaria pathology undetectable by conventional MRI

    PubMed Central

    von zur Muhlen, Constantin; Sibson, Nicola R.; Peter, Karlheinz; Campbell, Sandra J.; Wilainam, Panop; Grau, Georges E.; Bode, Christoph; Choudhury, Robin P.; Anthony, Daniel C.

    2008-01-01

    Human and murine cerebral malaria are associated with elevated levels of cytokines in the brain and adherence of platelets to the microvasculature. Here we demonstrated that the accumulation of platelets in the brain microvasculature can be detected with MRI, using what we believe to be a novel contrast agent, at a time when the pathology is undetectable by conventional MRI. Ligand-induced binding sites (LIBS) on activated platelet glycoprotein IIb/IIIa receptors were detected in the brains of malaria-infected mice 6 days after inoculation with Plasmodium berghei using microparticles of iron oxide (MPIOs) conjugated to a single-chain antibody specific for the LIBS (LIBS-MPIO). No binding of the LIBS-MPIO contrast agent was detected in uninfected animals. A combination of LIBS-MPIO MRI, confocal microscopy, and transmission electron microscopy revealed that the proinflammatory cytokine TNF-α, but not IL-1β or lymphotoxin-α (LT-α), induced adherence of platelets to cerebrovascular endothelium. Peak platelet adhesion was found 12 h after TNF-α injection and was readily detected with LIBS-MPIO contrast-enhanced MRI. Temporal studies revealed that the level of MPIO-induced contrast was proportional to the number of platelets bound. Thus, the LIBS-MPIO contrast agent enabled noninvasive detection of otherwise undetectable cerebral pathology by in vivo MRI before the appearance of clinical disease, highlighting the potential of targeted contrast agents for diagnostic, mechanistic, and therapeutic studies. PMID:18274670

  2. The delayed onset of subharmonic and ultraharmonic emissions from a phospholipid-shelled microbubble contrast agent

    PubMed Central

    Shekhar, Himanshu; Awuor, Ivy; Thomas, Keri; Rychak, Joshua J.; Doyley, Marvin M.

    2014-01-01

    Characterizing the nonlinear response of microbubble contrast agents is important for their efficacious use in imaging and therapy. In this paper, we report that the subharmonic and ultraharmonic response of lipid-shelled microbubble contrast agents exhibits a strong temporal dependence. We characterized nonlinear emissions from Targestar-P® microbubbles (Targeson Inc., San Diego, CA, USA) periodically for 60 minutes, at 10 MHz excitation frequency. The results revealed a considerable increase in the subharmonic and ultraharmonic response (nearly 12–15 and 5–8 dB) after 5–10 minutes of agent preparation. However, the fundamental and the harmonic response remained almost unchanged in this period. During the next 50 minutes, the subharmonic, fundamental, ultraharmonic, and harmonic responses decreased steadily by 2–5 dB. The temporal changes in the nonlinear behavior of the agent appeared to be primarily mediated by gas-exchange through the microbubble shell; temperature and prior acoustic excitation based mechanisms were ruled out. Further, there was no measurable change in the agent size distribution by static diffusion. We envisage that these findings will help obtain reproducible measurements from agent characterization, nonlinear imaging, and fluid-pressure sensing. These findings also suggest the possibility for improving nonlinear imaging by careful design of ultrasound contrast agents. PMID:24582298

  3. Towards a nanoscale mammographic contrast agent: development of a modular pre-clinical dual optical/x-ray agent

    NASA Astrophysics Data System (ADS)

    Hill, Melissa L.; Gorelikov, Ivan; Niroui, Farnaz; Levitin, Ronald B.; Mainprize, James G.; Yaffe, Martin J.; Rowlands, J. A.; Matsuura, Naomi

    2013-08-01

    Contrast-enhanced digital mammography (CEDM) can provide improved breast cancer detection and characterization compared to conventional mammography by imaging the effects of tumour angiogenesis. Current small-molecule contrast agents used for CEDM are limited by a short plasma half-life and rapid extravasation into tissue interstitial space. To address these limitations, nanoscale agents that can remain intravascular except at sites of tumour angiogenesis can be used. For CEDM, this agent must be both biocompatible and strongly attenuate mammographic energy x-rays. Nanoscale perfluorooctylbromide (PFOB) droplets have good x-ray attenuation and have been used in patients for other applications. However, the macroscopic scale of x-ray imaging (50-100 µm) is inadequate for direct verification that PFOB droplets localize at sites of breast tumour angiogenesis. For efficient pre-clinical optimization for CEDM, we integrated an optical marker into PFOB droplets for microscopic assessment (≪50 µm). To develop PFOB droplets as a new nanoscale mammographic contrast agent, PFOB droplets were labelled with fluorescent quantum dots (QDs). The droplets had mean diameters of 160 nm, fluoresced at 635 nm and attenuated x-ray spectra at 30.5 keV mean energy with a relative attenuation of 5.6 ± 0.3 Hounsfield units (HU) mg-1 mL-1 QD-PFOB. With the agent loaded into tissue phantoms, good correlation between x-ray attenuation and optical fluorescence was found (R2 = 0.96), confirming co-localization of the QDs with PFOB for quantitative assessment using x-ray or optical methods. Furthermore, the QDs can be removed from the PFOB agent without affecting its x-ray attenuation or structural properties for expedited translation of optimized PFOB droplet formulations into patients.

  4. Use of oral hypoglycemic and insulin agents in pregnant patients.

    PubMed

    Feldman, Deborah M; Fang, Yu Ming Victor

    2013-06-01

    Although insulin remains the standard medication for the treatment of all types of patients with diabetes during pregnancy, oral hypoglycemics may be considered as alternative medications in the treatment of some types of diabetes in pregnancy. PMID:23702114

  5. Plasmon-resonant gold nanorods as low backscattering albedo contrast agents for optical coherence tomography.

    PubMed

    Oldenburg, Amy L; Hansen, Matthew N; Zweifel, Daniel A; Wei, Alexander; Boppart, Stephen A

    2006-07-24

    Plasmon-resonant gold nanorods are demonstrated as low backscattering albedo contrast agents for optical coherence tomography (OCT). We define the backscattering albedo, a', as the ratio of the backscattering to extinction coefficient. Contrast agents which modify a' within the host tissue phantoms are detected with greater sensitivity by the differential OCT measurement of both a' and extinction. Optimum sensitivity is achieved by maximizing the difference between contrast agents and tissue, |a'(ca) - a'(tiss)|. Low backscattering albedo gold nanorods (14x 44 nm; lambda(max) = 780 nm) within a high backscattering albedo tissue phantom with an uncertainty in concentration of 20% (randomized 2+/-0.4% intralipid) were readily detected at 82 ppm (by weight) in a regime where extinction alone could not discriminate nanorods. The estimated threshold of detection was 30 ppm. PMID:19516854

  6. Microbubble embedded with upconversion nanoparticles as a bimodal contrast agent for fluorescence and ultrasound imaging

    NASA Astrophysics Data System (ADS)

    Jin, Birui; Lin, Min; You, Minli; Zong, Yujin; Wan, Mingxi; Xu, Feng; Duan, Zhenfeng; Lu, Tianjian

    2015-08-01

    Bimodal imaging offers additional imaging signal thus finds wide spread application in clinical diagnostic imaging. Fluorescence/ultrasound bimodal imaging contrast agent using fluorescent dyes or quantum dots for fluorescence signal has emerged as a promising method, which however requires visible light or UV irradiation resulting in photobleaching, photoblinking, auto-fluorescence and limited tissue penetration depth. To surmount these problems, we developed a novel bimodal contrast agent using layer-by-layer assembly of upconversion nanoparticles onto the surface of microbubbles. The resulting microbubbles with average size of 2 μm provide enhanced ultrasound echo for ultrasound imaging and upconversion emission upon near infrared irradiation for fluorescence imaging. The developed bimodal contrast agent holds great potential to be applied in ultrasound target technique for targeted diseases diagnostics and therapy.

  7. Molecular MR Contrast Agents for the Detection of Cancer: Past and Present

    PubMed Central

    Bogdanov, Alexei; Mazzanti, Mary L.

    2011-01-01

    Magnetic resonance imaging (MRI) is a powerful diagnostic tool capable of providing detailed information about the structure and composition of tumors, with unsurpassed spatial resolution. The use of exogenously administered contrast agents allows compartment-specific enhancement of tumors, enabling imaging of functional blood and interstitial volumes. Current efforts are directed at enhancing the capabilities of MRI in oncology to add contrast agents with molecular specificities to the growing armamentarium of diagnostic probes capable of changing local proton relaxation times as a consequence of specific contrast agent binding to cell surface receptors or extracellular matrix components. We review herein the most notable examples, illustrating major trends in the development of specific probes for high-resolution imaging in molecular oncology. PMID:21362515

  8. A spatially-distributed computational model to quantify behaviour of contrast agents in MR perfusion imaging

    PubMed Central

    Cookson, A.N.; Lee, J.; Michler, C.; Chabiniok, R.; Hyde, E.; Nordsletten, D.; Smith, N.P.

    2014-01-01

    Contrast agent enhanced magnetic resonance (MR) perfusion imaging provides an early, non-invasive indication of defects in the coronary circulation. However, the large variation of contrast agent properties, physiological state and imaging protocols means that optimisation of image acquisition is difficult to achieve. This situation motivates the development of a computational framework that, in turn, enables the efficient mapping of this parameter space to provide valuable information for optimisation of perfusion imaging in the clinical context. For this purpose a single-compartment porous medium model of capillary blood flow is developed which is coupled with a scalar transport model, to characterise the behaviour of both blood-pool and freely-diffusive contrast agents characterised by their ability to diffuse through the capillary wall into the extra-cellular space. A parameter space study is performed on the nondimensionalised equations using a 2D model for both healthy and diseased myocardium, examining the sensitivity of system behaviour to Peclet number, Damköhler number (Da), diffusivity ratio and fluid porosity. Assuming a linear MR signal response model, sample concentration time series data are calculated, and the sensitivity of clinically-relevant properties of these signals to the model parameters is quantified. Both upslope and peak values display significant non-monotonic behaviour with regard to the Damköhler number, with these properties showing a high degree of sensitivity in the parameter range relevant to contrast agents currently in use. However, the results suggest that signal upslope is the more robust and discerning metric for perfusion quantification, in particular for correlating with perfusion defect size. Finally, the results were examined in the context of nonlinear signal response, flow quantification via Fermi deconvolution and perfusion reserve index, which demonstrated that there is no single best set of contrast agent parameters

  9. Numerical Modeling of 3-D Dynamics of Ultrasound Contrast Agent Microbubbles Using the Boundary Integral Method

    NASA Astrophysics Data System (ADS)

    Calvisi, Michael; Manmi, Kawa; Wang, Qianxi

    2014-11-01

    Ultrasound contrast agents (UCAs) are microbubbles stabilized with a shell typically of lipid, polymer, or protein and are emerging as a unique tool for noninvasive therapies ranging from gene delivery to tumor ablation. The nonspherical dynamics of contrast agents are thought to play an important role in both diagnostic and therapeutic applications, for example, causing the emission of subharmonic frequency components and enhancing the uptake of therapeutic agents across cell membranes and tissue interfaces. A three-dimensional model for nonspherical contrast agent dynamics based on the boundary integral method is presented. The effects of the encapsulating shell are approximated by adapting Hoff's model for thin-shell, spherical contrast agents to the nonspherical case. A high-quality mesh of the bubble surface is maintained by implementing a hybrid approach of the Lagrangian method and elastic mesh technique. Numerical analyses for the dynamics of UCAs in an infinite liquid and near a rigid wall are performed in parameter regimes of clinical relevance. The results show that the presence of a coating significantly reduces the oscillation amplitude and period, increases the ultrasound pressure amplitude required to incite jetting, and reduces the jet width and velocity.

  10. Synthesis, Characterization, and in vitro Testing of a Bacteria-Targeted MR Contrast Agent

    PubMed Central

    Matosziuk, Lauren M.; Harney, Allison S.; MacRenaris, Keith W.

    2013-01-01

    A bacteria-targeted MR contrast agent, Zn-1, consisting of two Zn-dipicolylamine (Zn-dpa) groups conjugated to a GdIII chelate has been synthesized and characterized. In vitro studies with S. aureus and E. coli show that Zn-1 exhibits a significant improvement in bacteria labeling efficiency vs. control. Studies with a structural analogue, Zn-2, indicate that removal of one Zn-dpa moiety dramatically reduces the agent's affinity for bacteria. The ability of Zn-1 to significantly reduce the T1 of labeled vs. unlabeled bacteria, resulting in enhanced MR image contrast, demonstrates its potential for visualizing bacterial infections in vivo. PMID:23626484

  11. Preclinical evaluation of biodegradable macromolecular contrast agents for magnetic resonance imaging

    NASA Astrophysics Data System (ADS)

    Feng, Yi

    Macromolecular contrast agents have been shown to be superior to small molecular weight contrast agents for MRI in blood pool imaging, tumor diagnosis and grading. However, none has been approved by the FDA because they circulate in the bloodstream much longer than small molecular weight contrast agents and result in high tissue accumulation of toxic Gd(III) ions. Biodegradable macromolecular contrast agents (BMCA) were invented to alleviate the toxic accumulation. They have a cleavable disulfide bond based backbone that can be degraded in vivo and excreted out of the body via renal filtration. Furthermore, the side chain of the backbone can be modified to achieve various degradation rates. Three BMCA, (Gd-DTPA)-cystamine copolymers (GDCC), Gd-DTPA cystine copolymers (GDCP), and Gd-DTPA cystine diethyl ester copolymers (GDCEP), were evaluated as blood pool contrast agents in a rat model. They have excellent blood pool enhancement, preferred pharmacokinetics, and only minimal long-term tissue retention of toxic Gd(III) ions. GDCC and GDCP, the lead agents with desired degradation rates, with molecular weights of 20 KDa and 70 KDa, were chosen for dynamic contrast enhanced MRI (DCE-MRI) to differentiate human prostate tumor models of different malignancy and growth rates. GDCC and GDCP could differentiate these tumor models, providing more accurate estimations of plasma volume, flow leakage rate, and permeability surface area product than a small molecular weight contrast agent Gd-DTPA-BMA when compared to the prototype macromolecular contrast agent albumin-Gd-DTPA. GDCC was favored for its neutral charge side chain and reasonable uptake rate by the tumors. GDCC with a molecular weight of 40 KDa (GDCC-40, above the renal filtration cutoff size) was used to assess the efficacy of two photothermal therapies (interstitial and indocyanine green enhanced). GDCC-40 provided excellent tumor enhancement shortly after its injection. Acute tumor response (4 hr) after therapies

  12. Brain nuclear magnetic resonance imaging enhanced by a paramagnetic nitroxide contrast agent: preliminary report. [Dogs

    SciTech Connect

    Brasch, R.C.; Nitecki, D.E.; Brant-Zawadzki, M.; Enzmann, D.R.; Wesbey, G.E.; Tozer, T.N.; Tuck, L.D.; Cann, C.E.; Fike, J.R.; Sheldon, P.

    1983-11-01

    Contrast-enhancing agents for demonstrating abnormalities of the blood-brain barrier may extend the diagnostic utility of proton nuclear magnetic resonance (NMR) imaging. TES, a nitroxide stable free radical derivative, was tested as a central nervous system contrast enhancer in dogs with experimentally induced unilateral cerebritis or radiation cerebral damage. After intravenous injection of TES, the normal brain showed no change in NMR appearance, but areas of disease demonstrated a dramatic increase (up to 45%) in spin-echo intensity and a decrease in T/sub 1/, relaxation times. The areas of disease defined by TES enhancement were either not evident on the nonenhanced NMR images or were better defined after contrast administration. In-depth tests of toxicity, stability, and metabolism of this promising NMR contrast agent are now in progress.

  13. Combined ultrasound and photoacoustic imaging of pancreatic cancer using nanocage contrast agents

    NASA Astrophysics Data System (ADS)

    Homan, Kimberly; Shah, Jignesh; Gomez, Sobeyda; Gensler, Heidi; Karpiouk, Andrei; Brannon-Peppas, L.; Emelianov, Stanislav

    2009-02-01

    A new metallodielectric nanoparticle consisting of a silica core and silver outer cage was developed for the purpose of enhancing photoacoustic imaging contrast in pancreatic tissue. These nanocages were injected into an ex vivo porcine pancreas and imaged using a combined photoacoustic and ultrasound (PAUS) assembly. This custom-designed PAUS assembly delivered 800 nm light through a fiber optical light delivery system integrated with 128 element linear array transducer operating at 7.5 MHz center frequency. Imaging results prove that the nanocage contrast agents have the ability to enhance photoacoustic imaging contrast. Furthermore, the value of the combined PAUS imaging modality was demonstrated as the location of nanocages against background native tissue was evident. Future applications of these nanocage contrast agents could include targeting them to pancreatic cancer for enhancement of photoacoustic imaging for diagnosis and therapy.

  14. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods

    PubMed Central

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-01-01

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used. PMID:27185492

  15. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods

    NASA Astrophysics Data System (ADS)

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-05-01

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used.

  16. Improved sensitivity of computed tomography towards iodine and gold nanoparticle contrast agents via iterative reconstruction methods.

    PubMed

    Bernstein, Ally Leigh; Dhanantwari, Amar; Jurcova, Martina; Cheheltani, Rabee; Naha, Pratap Chandra; Ivanc, Thomas; Shefer, Efrat; Cormode, David Peter

    2016-01-01

    Computed tomography is a widely used medical imaging technique that has high spatial and temporal resolution. Its weakness is its low sensitivity towards contrast media. Iterative reconstruction techniques (ITER) have recently become available, which provide reduced image noise compared with traditional filtered back-projection methods (FBP), which may allow the sensitivity of CT to be improved, however this effect has not been studied in detail. We scanned phantoms containing either an iodine contrast agent or gold nanoparticles. We used a range of tube voltages and currents. We performed reconstruction with FBP, ITER and a novel, iterative, modal-based reconstruction (IMR) algorithm. We found that noise decreased in an algorithm dependent manner (FBP > ITER > IMR) for every scan and that no differences were observed in attenuation rates of the agents. The contrast to noise ratio (CNR) of iodine was highest at 80 kV, whilst the CNR for gold was highest at 140 kV. The CNR of IMR images was almost tenfold higher than that of FBP images. Similar trends were found in dual energy images formed using these algorithms. In conclusion, IMR-based reconstruction techniques will allow contrast agents to be detected with greater sensitivity, and may allow lower contrast agent doses to be used. PMID:27185492

  17. A self-calibrating PARACEST MRI contrast agent that detects esterase enzyme activity

    PubMed Central

    Li, Yuguo; Sheth, Vipul R.; Liu, Guanshu; Pagel, Mark D.

    2016-01-01

    The CEST effect of many PARACEST MRI contrast agents changes in response to a molecular biomarker. However, other molecular biomarkers or environmental factors can influence CEST, so that a change in CEST is not conclusive proof for detecting the biomarker. To overcome this problem, a second control CEST effect may be included in the same PARACEST agent, which is responsive to all factors that alter the first CEST effect except for the biomarker to be measured. To investigate this approach, a PARACEST MRI contrast agent was developed with one CEST effect that is responsive to esterase enzyme activity and a second control CEST effect. The ratio of the two CEST effects was independent of concentration and T1 relaxation, so that this agent was self-calibrating with respect to these factors. This ratiometric method was dependent on temperature and was influenced by MR coalescence as the chemical exchange rates approached the chemical shifts of the exchangable protons as temperature was increased. The two CEST effects also showed evidence of having different pH dependencies, so that this agent was not self-calibrating with respect to pH. Therefore, a self-calibrating PARACEST MRI contrast agent can more accurately detect a molecular biomarker such as esterase enzyme activity, as long as temperature and pH are within an acceptable physiological range and remain constant. PMID:21861282

  18. Single-walled carbon nanotubes as a multimodal — thermoacoustic and photoacoustic — contrast agent

    PubMed Central

    Pramanik, Manojit; Swierczewska, Magdalena; Green, Danielle; Sitharaman, Balaji; Wang, Lihong V.

    2009-01-01

    We have developed a novel carbon nanotube-based contrast agent for both thermoacoustic and photoacoustic tomography. In comparison with de-ionized water, single-walled carbon nanotubes exhibited more than two-fold signal enhancement for thermoacoustic tomography at 3 GHz. In comparison with blood, they exhibited more than six-fold signal enhancement for photoacoustic tomography at 1064 nm wavelength. The large contrast enhancement of single-walled carbon nanotubes was further corroborated by tissue phantom imaging studies. PMID:19566311

  19. Experimental and theoretical x-ray imaging performance comparison of iodine and lanthanide contrast agents.

    PubMed

    Cardinal, H N; Holdsworth, D W; Drangova, M; Hobbs, B B; Fenster, A

    1993-01-01

    Contrast agents based on the lanthanide elements gadolinium and holmium have recently been developed for magnetic resonance imaging (MRI). Because of the increased atomic number of these elements relative to iodine, these new compounds, used as x-ray contrast agents, may yield higher radiographic contrast, and hence improved x-ray image quality, relative to conventional iodinated compounds, for clinically useful x-ray spectra. This possibility has been investigated, in independent experimental and theoretical studies, for two x-ray imaging systems: a digital radiographic system, using an x-ray image intensifier (XRII) and charge-coupled device (CCD) detector; and a conventional screen/film system, using a Lanex Regular screen. Iodine, gadolinium, and holmium contrast agents were investigated over a wide range of concentration-thickness products (0.1-0.6 M cm) and diagnostic x-ray spectra (60-120 kVp). A simple theoretical model of x-ray detector response predicts the experimental radiographic contrast measurements with a mean absolute error of 8.0% for the XRII/CCD system and 5.9% for the screen/film system, and shows that the radiographic contrast for these two systems is representative of all XRII and screen/film systems. An index of image quality is defined, and its dependence on radiographic contrast, x-ray fluence per unit dose, and detective quantum efficiency (DQE) is shown. Theoretical values of the index, predicted by our model, are then used to compare the performance of the three contrast agents for the two systems investigated. In general, iodine performance decreases steadily with increasing kVp, gadolinium performance has a broad maximum near 85 kVp, and gadolinium outperforms holmium. Gadolinium outperforms iodine for spectra above (and vice versa below) about 72 kVp, depending slightly on spectrum filtration, object thickness, and detector type. Thus, raising the kVp to shorten exposure times or reduce x-ray tube heat loading results in a loss of

  20. Blackberry (Rubus spp.): a pH-dependent oral contrast medium for gastrointestinal tract images by magnetic resonance imaging.

    PubMed

    Espinosa, María G; Sosa, Modesto; De León-Rodríguez, Luis M; Córdova, Teodoro; Bernal-Alvarado, Jesus; Avila-Rodríguez, Mario; Reyes-Aguilera, Jose A; Ortíz, Juan J; Barrios, Fernando A

    2006-02-01

    In this study, seven fruits have been tested on their magnetic properties, paramagnetic metal content and contrast enhancement in magnetic resonance imaging (MRI) of phantom and in vivo. Magnetic susceptibility was determined for the fruit pulps, as well as the contents of paramagnetic metals; iron, manganese and copper. The total content of these metals was 4.3, 8.6, 11.1, 10.9, 12.3, 8.3 and 29.3 mg/kg of fruit for plum, blueberry, apple (red), pineapple, beet, grape, blackberry, respectively, and with magnetic susceptibility of -2.29+/-0.07, -2.43+/-0.07, -2.13+/-0.07, -1.84+/-0.02, -1.75+/-0.01, -1.78+/-0.06, -2.18+/-0.07 SI, respectively. T(1)- and T(2)-weighted MR images were performed for the seven fruits and water (chi= -9.98 x 10(-3) SI) and in one subject. While there was no correlation between the magnetic susceptibility and contrast enhancement, there is a correlation with the total paramagnetic metal content determined with contrast enhancement in MRI. Thus, blackberry (Rubus spp.) contrast enhancement was the highest among the fruits in T(1)-weighted images. Furthermore, this fruit's contrast enhancement shows to be pH-dependent. These characteristics and the wide availability of the Rubus spp. suggest that it should be implemented as an oral contrast agent in images by MR to assess the function of the gastric section of the GI tract. Furthermore, it has the advantage of being a natural meal, so that it can be well tolerated by the patients and use as much as it is needed without side effects. PMID:16455409

  1. Acoustic characterization and pharmacokinetic analyses of new nanobubble ultrasound contrast agents.

    PubMed

    Wu, Hanping; Rognin, Nicolas G; Krupka, Tianyi M; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christopher; Kamiyama, Naohisa; Exner, Agata A

    2013-11-01

    In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rates in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within

  2. ACOUSTIC CHARACTERIZATION AND PHARAMACOKINETIC ANALYSES OF NEW NANOBUBBLE ULTRASOUND CONTRAST AGENTS

    PubMed Central

    Wu, Hanping; Rognin, Nicolas G.; Krupka, Tianyi M.; Solorio, Luis; Yoshiara, Hiroki; Guenette, Gilles; Sanders, Christoher; Kamiyama, Naohisa; Exner, Agata A.

    2013-01-01

    In contrast to the clinically used microbubble ultrasound contrast agents, nanoscale bubbles (or nanobubbles) may potentially extravasate into tumors that exhibit more permeable vasculature, facilitating targeted molecular imaging and drug delivery. Our group recently presented a simple strategy using the non-ionic surfactant Pluronic as a size control excipient to produce nanobubbles with a mean diameter of 200 nm that exhibited stability and echogenicity on par with microbubbles. The objective of this study was to carry out an in-depth characterization of nanobubble properties as compared with Definity microbubbles, both in vitro and in vivo. Through use of a tissue-mimicking phantom, in vitro experiments measured the echogenicity of the contrast agent solutions and the contrast agent dissolution rate over time. Nanobubbles were found to be more echogenic than Definity microbubbles at three different harmonic frequencies (8, 6.2 and 3.5 MHz). Definity microbubbles also dissolved 1.67 times faster than nanobubbles. Pharmacokinetic studies were then performed in vivo in a subcutaneous human colorectal adenocarcinoma (LS174T) in mice. The peak enhancement and decay rates of contrast agents after bolus injection in the liver, kidney and tumor were analyzed. No significant differences were observed in peak enhancement between the nanobubble and Definity groups in the three tested regions (tumor, liver and kidney). However, the decay rates of nanobubbles in tumor and kidney were significantly slower than those of Definity in the first 200-s fast initial phase. There were no significant differences in the decay rate in the liver in the initial phase or in three regions of interest in the terminal phase. Our results suggest that the stability and acoustic properties of the new nanobubble contrast agents are superior to those of the clinically used Definity microbubbles. The slower washout of nanobubbles in tumors suggests potential entrapment of the bubbles within the

  3. Characterization of novel molecular photoacoustic contrast agents for in vivo photoacoustic tomography

    NASA Astrophysics Data System (ADS)

    Laoui, Samir

    Photoacoustic tomography is a hybrid imaging modality that takes advantage of the high contrast of pure optical imaging and the high intrinsic resolution of ultrasound without the necessity of ionizing radiation. Photoacoustic imaging (PM) is neither purely optical nor purely acoustical in nature, but a combination of the two. It is fundamentally based on light excitation and ultrasonic detection. Photoacoustic imaging has been successful without the introduction of exogenous contrast agents; however, to image deeper regions of biological tissue, a contrast agent is necessary. Several types of photoacoustic contrast agents have been made available for diagnostic purposes; however, the majority of literature has focused on gold nanoparticle systems for which the surface-plasmon resonance effect is important. The only option currently available for molecular PM contrast agents is to choose an existing near infrared absorbing fluorescent probes with the hope that they may generate a substantial photoacoustic (PA) response. However, these dyes have been designed with an optimized fluorescence emission response and are not anticipated to generate an adequate photoacoustic response. This dissertation addresses this lack of precedence in the literature for understanding the mechanism of a photoacoustic signal generation from strongly absorbing dye molecules including BODIPY, cyanine and curcumin systems. This work represents preliminary efforts in bringing novel molecular photoacoustic contrast agents (MPACs) into the photoacoustic imaging arena. To this end, photoacoustic and optical Z-scan experiments, and quenching studies were employed to demonstrate correlation of photoacoustic emission enhancement with excited state absorption mechanisms. To investigate further the photoacoustic emission in a practical imaging setting, MPACs were imaged using a recently developed photoacoustic imaging tomography system which was constructed exclusively for the purpose of this study.

  4. Silica-coated bismuth sulfide nanorods as multimodal contrast agents for a non-invasive visualization of the gastrointestinal tract

    NASA Astrophysics Data System (ADS)

    Zheng, Xiaopeng; Shi, Junxin; Bu, Yang; Tian, Gan; Zhang, Xiao; Yin, Wenyan; Gao, Bifen; Yang, Zhiyong; Hu, Zhongbo; Liu, Xiangfeng; Yan, Liang; Gu, Zhanjun; Zhao, Yuliang

    2015-07-01

    Non-invasive and real-time imaging of the gastrointestinal (GI) tract is particularly desirable for research and clinical studies of patients with symptoms arising from gastrointestinal diseases. Here, we designed and fabricated silica-coated bismuth sulfide nanorods (Bi2S3@SiO2 NRs) for a non-invasive spatial-temporally imaging of the GI tract. The Bi2S3 NRs were synthesized by a facile solvothermal method and then coated with a SiO2 layer to improve their biocompatibility and stability in the harsh environments of the GI tract, such as the stomach and the small intestine. Due to their strong X-ray- and near infrared-absorption abilities, we demonstrate that, following oral administration in mice, the Bi2S3@SiO2 NRs can be used as a dual-modal contrast agent for the real-time and non-invasive visualization of NRs distribution and the GI tract via both X-ray computed tomography (CT) and photoacoustic tomography (PAT) techniques. Importantly, integration of PAT with CT provides complementary information on anatomical details with high spatial resolution. In addition, we use Caenorhabditis Elegans (C. Elegans) as a simple model organism to investigate the biological response of Bi2S3@SiO2 NRs by oral administration. The results indicate that these NRs can pass through the GI tract of C. Elegans without inducing notable toxicological effects. The above results suggest that Bi2S3@SiO2 NRs pave an alternative way for the fabrication of multi-modal contrast agents which integrate CT and PAT modalities for a direct and non-invasive visualization of the GI tract with low toxicity.Non-invasive and real-time imaging of the gastrointestinal (GI) tract is particularly desirable for research and clinical studies of patients with symptoms arising from gastrointestinal diseases. Here, we designed and fabricated silica-coated bismuth sulfide nanorods (Bi2S3@SiO2 NRs) for a non-invasive spatial-temporally imaging of the GI tract. The Bi2S3 NRs were synthesized by a facile

  5. Specific binding of molecularly targeted agents to pancreas tumors and impact on observed optical contrast

    NASA Astrophysics Data System (ADS)

    Samkoe, Kimberley S.; Hextrum, Shannon K.; Pardesi, Omar; O'Hara, Julia A.; Hasan, Tayyaba; Pogue, Brian W.

    2010-02-01

    In optical imaging it is thought that optimum tumor contrast can be achieved with the use of small-labeled molecular tracers that have high affinity to their targets and fast clearance rates from the blood stream and healthy tissues. An example of this is fluorescently tagged EGF to monitor the molecular activity of tumors, such as pancreatic cancer. Extensive fluorescence contrast analysis for fluorescence molecular tomography has been performed on the AsPC-1 pancreas tumor, grown orthotopically in mice; yet, the binding dynamics of the EGF-fluorescent agent in vivo is not completely known. The bulk pancreatic tumor displays 3:1 contrast relative to the normal pancreas at long times after injection; however, even higher levels of fluorescence in the liver, kidney and intestine suggest that molecular specificity for the tumor may be low. Mice were administered a fluorescently labeled EGF agent and were sacrificed at various time points post-injection. To analyze the amount of specific binding at each time point frozen tissue samples were fluorescently imaged, washed with saline to remove the interstitially distributed contrast agent, and then imaged again. This technique demonstrated that approximately ~10% of the molecular target was firmly bound to the cell, while 90% was mobile or unbound. This low binding ratio suggests that the contrast observed is from inherent properties of the tumor (i.e. enhanced permeability and retention effect) and not from specific bound contrast as previously anticipated. The use of EGF contrast agents in MRI-guided fluorescence tomography and the impact of low binding specificity are discussed.

  6. Absolute perfusion measurements and associated iodinated contrast agent time course in brain metastasis: a study for contrast-enhanced radiotherapy

    PubMed Central

    Obeid, Layal; Deman, Pierre; Tessier, Alexandre; Balosso, Jacques; Estève, François; Adam, Jean- François

    2014-01-01

    Contrast-enhanced radiotherapy is an innovative treatment that combines the selective accumulation of heavy elements in tumors with stereotactic irradiations using medium energy X-rays. The radiation dose enhancement depends on the absolute amount of iodine reached in the tumor and its time course. Quantitative, postinfusion iodine biodistribution and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. Twelve patients received an intravenous bolus of iodinated contrast agent (CA) (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multislice dynamic computed tomography (CT) images of the brain. The postinfusion mean intratumoral iodine concentration (over 30 minutes) reached 1.94±0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. To our knowledge, this is the first quantitative study of CA biodistribution versus time in brain metastasis. The study shows that suitable and stable amounts of iodine can be reached for contrast-enhanced radiotherapy. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes. PMID:24447951

  7. Gold-coated iron oxide nanoparticles as a T2 contrast agent in magnetic resonance imaging.

    PubMed

    Ahmad, Tanveer; Bae, Hongsub; Rhee, Ilsu; Chang, Yongmin; Jin, Seong-Uk; Hong, Sungwook

    2012-07-01

    Gold-coated iron oxide (Fe3O4) nanoparticles were synthesized for use as a T2 contrast agent in magnetic resonance imaging (MRI). The coated nanoparticles were spherical in shape with an average diameter of 20 nm. The gold shell was about 2 nm thick. The bonding status of the gold on the nanoparticle surfaces was checked using a Fourier transform infrared spectrometer (FTIR). The FTIR spectra confirmed the attachment of homocysteine, in the form of thiolates, to the Au shell of the Au-Fe3O4 nanoparticles. The relaxivity ratio, R2/R1, for the coated nanoparticles was 3-fold higher than that of a commercial contrast agent, Resovist, which showed the potential for their use as a T2 contrast agent with high efficacy. In animal experiments, the presence of the nanoparticles in rat liver resulted in a 71% decrease in signal intensity in T2-weighted MR images, indicating that our gold-coated iron oxide nanoparticles are suitable for use as a T2 contrast agent in MRI. PMID:22966533

  8. Hypoxia targeted carbon nanotubes as a sensitive contrast agent for photoacoustic imaging of tumors

    NASA Astrophysics Data System (ADS)

    Zanganeh, Saeid; Aguirre, Andres; Biswal, Nrusingh C.; Pavlik, Christopher; Smith, Michael B.; Alqasemi, Umar; Li, Hai; Zhu, Quing

    2011-03-01

    Development of new and efficient contrast agents is of fundamental importance to improve detection sensitivity of smaller lesions. Within the family of nanomaterials, carbon nanotubes (CNT) not only have emerged as a new alternative and efficient transporter and translocater of therapeutic molecules but also as a photoacoustic molecular imaging agent owing to its strong optical absorption in the near-infrared region. Drugs, Antibodies and nucleic acids could functionalize the CNT and prepare an appropriate system for delivering the cargos to cells and organs. In this work, we present a novel photoacoustic contrast agent which is based on a unique hypoxic marker in the near infrared region, 2-nitroimidazole -bis carboxylic acid derivative of Indocyanine Green conjugated to single walled carbon nanotube (SWCNT-2nitroimidazole-ICG). The 2-nitroimidazole-ICG has an absorption peak at 755 nm and an extinction coefficient of 20,5222 M-1cm-1. The conjugation of this marker with SWCNT shows more than 25 times enhancement of optical absorption of carbon nanotubes in the near infrared region. This new conjugate has been optically evaluated and shows promising results for high contrast photoacoustic imaging of deeply located tumors. The conjugate specifically targets tumor hypoxia, an important indicator of tumor metabolism and tumor therapeutic response. The detection sensitivity of the new contrast agent has been evaluated in-vitro cell lines and with in-vivo tumors in mice.

  9. Azoimidazole functionalized Ni-porphyrins for molecular spin switching and light responsive MRI contrast agents.

    PubMed

    Heitmann, Gernot; Schütt, Christian; Gröbner, Jens; Huber, Lukas; Herges, Rainer

    2016-07-28

    Azo-N-methylimidazole functionalized Ni(ii)porphyrins were rationally designed and synthesized and their performance as molecular spin switches was investigated. They perform intramolecular light-driven coordination-induced spin state switching (LD-CISSS) in the presence of water and therefore are an important step towards spin switches for medicinal applications, particularly functional MRI contrast agents. PMID:27334263

  10. Functional Hyperbranched Polylysine as Potential Contrast Agent Probes for Magnetic Resonance Imaging.

    PubMed

    Zu, Guangyue; Liu, Min; Zhang, Kunchi; Hong, Shanni; Dong, Jingjin; Cao, Yi; Jiang, Bin; Luo, Liqiang; Pei, Renjun

    2016-06-13

    Researchers have never stopped questing contrast agents with high resolution and safety to overcome the drawbacks of small-molecule contrast agents in clinic. Herein, we reported the synthesis of gadolinium-based hyperbranched polylysine (HBPLL-DTPA-Gd), which was prepared by thermal polymerization of l-lysine via one-step polycondensation. After conjugating with folic acid, its potential application as MRI contrast agent was then evaluated. This contrast agent had no obvious cytotoxicity as verified by WST assay and H&E analysis. Compared to Gd(III)-diethylenetriaminepentaacetic acid (Gd-DTPA) (r1 = 4.3 mM(-1) s(-1)), the FA-HBPLL-DTPA-Gd exhibited much higher longitudinal relaxivity value (r1 = 13.44 mM(-1) s(-1)), up to 3 times higher than Gd-DTPA. The FA-HBPLL-DTPA-Gd showed significant signal intensity enhancement in the tumor region at various time points and provided a long time window for MR examination. The results illustrate that FA-HBPLL-DTPA-Gd will be a potential candidate for tumor-targeted MRI. PMID:27187578

  11. MRI contrast agent delivery using spore capsules: controlled release in blood plasma.

    PubMed

    Lorch, Mark; Thomasson, Matthew J; Diego-Taboada, Alberto; Barrier, Sylvain; Atkin, Stephen L; Mackenzie, Grahame; Archibald, Stephen J

    2009-11-14

    The exine coatings of spores can be used to encapsulate drug molecules. We have demonstrated that these microcapsules can be filled with a commercial gadolinium(III) MRI contrast agent (in this proof of concept study Gd-DTPA-BMA was used) which is slowly released in plasma due to enzymatic digestion of the capsule. PMID:19841803

  12. Counterbalancing the use of ultrasound contrast agents by a cavitation-regulated system.

    PubMed

    Desjouy, C; Fouqueray, M; Lo, C W; Muleki Seya, P; Lee, J L; Bera, J C; Chen, W S; Inserra, C

    2015-09-01

    The stochastic behavior of cavitation can lead to major problems of initiation and maintenance of cavitation during sonication, responsible of poor reproducibility of US-induced bioeffects in the context of sonoporation for instance. To overcome these disadvantages, the injection of ultrasound contrast agents as cavitation nuclei ensures fast initiation and lower acoustic intensities required for cavitation activity. More recently, regulated-cavitation devices based on the real-time modulation of the applied acoustic intensity have shown their potential to maintain a stable cavitation state during an ultrasonic shot, in continuous or pulsed wave conditions. In this paper is investigated the interest, in terms of cavitation activity, of using such regulated-cavitation device or injecting ultrasound contrast agents in the sonicated medium. When using fixed applied acoustic intensity, results showed that introducing ultrasound contrast agents increases reproducibility of cavitation activity (coefficient of variation 62% and 22% without and with UCA, respectively). Moreover, the use of the regulated-cavitation device ensures a given cavitation activity (coefficient of variation less 0.4% in presence of UCAs or not). This highlights the interest of controlling cavitation over time to free cavitation-based application from the use of UCAs. Interestingly, during a one minute sonication, while ultrasound contrast agents progressively disappear, the regulated-cavitation device counterbalance their destruction to sustain a stable inertial cavitation activity. PMID:25682465

  13. Dynamic assessment of the focal hepatic lesion in rats using ultrasonic contrast agent.

    PubMed

    Zhang, Chao; Deng, Youbin; Huang, Daozhong; Zhang, Qingping

    2006-01-01

    The focal hepatic lesion caused by local injection of absolute alcohol in rats was evaluated with ultrasonic contrast agent and pathologic examination. Twenty adult Wistar rats weighing about 200 g were injected with absolute alcohol (0.05-0.1 mL each one) on the exterior left lobe of the liver under the monitoring of ultrasound. Pulse inversion harmonic imaging was used to evaluate the focal lesion after bolus injection of ultrasonic contrast agent (0.05 mL/200 g) through caudal vein. Seven days later, the focal lesion was studied again as before. The exterior left lobe of liver with focal lesion was incised and underwent pathologic examination. The results showed that all of the focal lesions could be defined clearly after bolus injection of the ultrasonic contrast agent under the mode of pulse inversion harmonic imaging. There was good correlation between the size of the focal lesion measured by ultrasound on the 7th day after the "ablation" under the mode of pulse inversion harmonic imaging and that gotten by pathologic examination (P = 0.39). The focus size measured by ultrasound right after the ablation was larger than that gotten by pathologic examination (P = 0.002). It was concluded that ultrasonic contrast agent plus pulse inversion harmonic imaging could be used to assess the size of the focal hepatic lesion caused by local injection of absolute alcohol in rats. PMID:16961285

  14. In vivo small animal micro-CT using nanoparticle contrast agents

    PubMed Central

    Ashton, Jeffrey R.; West, Jennifer L.; Badea, Cristian T.

    2015-01-01

    Computed tomography (CT) is one of the most valuable modalities for in vivo imaging because it is fast, high-resolution, cost-effective, and non-invasive. Moreover, CT is heavily used not only in the clinic (for both diagnostics and treatment planning) but also in preclinical research as micro-CT. Although CT is inherently effective for lung and bone imaging, soft tissue imaging requires the use of contrast agents. For small animal micro-CT, nanoparticle contrast agents are used in order to avoid rapid renal clearance. A variety of nanoparticles have been used for micro-CT imaging, but the majority of research has focused on the use of iodine-containing nanoparticles and gold nanoparticles. Both nanoparticle types can act as highly effective blood pool contrast agents or can be targeted using a wide variety of targeting mechanisms. CT imaging can be further enhanced by adding spectral capabilities to separate multiple co-injected nanoparticles in vivo. Spectral CT, using both energy-integrating and energy-resolving detectors, has been used with multiple contrast agents to enable functional and molecular imaging. This review focuses on new developments for in vivo small animal micro-CT using novel nanoparticle probes applied in preclinical research. PMID:26581654

  15. Prolonged in vivo circulation time by zwitterionic modification of magnetite nanoparticles for blood pool contrast agents.

    PubMed

    Xiao, Wangchuan; Lin, Jiang; Li, Mingli; Ma, Yongjie; Chen, Yuxin; Zhang, Chunfu; Li, Dan; Gu, Hongchen

    2012-01-01

    Long circulation time is critical for blood pool contrast agents used in high-resolution magnetic resonance angiography. For iron oxide particle contrast agents, size and surface properties significantly influence their in vivo performance. We developed a novel long-circulating blood pool contrast agent by introducing zwitterionic structure onto the particle surface. Zwitterionic structure was fabricated by 3-(diethylamino)propylamine (DEAPA) grafted onto the surface of ployacrylic acid coated magnetite nanoparticles via EDC/NHS [N-(3-dimethylaminopropyl)-N'-ethylcarbo-diimide hydrochloride/N-hydroxysuccinimide] coupling chemistry. Zwitterionic particles demonstrated five times lower macrophage cell uptake than the original particles and low cell toxicity. Magnetic resonance angiography indicated that zwitterionic nanoparticles had much longer in vivo circulation time than the original particles and were an ideal candidate for blood pool contrast agent. We suppose that zwitterionic modification by DEAPA and EDC/NHS can be used generally for coating nanoparticles with carboxyl surface and to prolong their circulating time. PMID:22539402

  16. Mechanistic studies of Gd3+-based MRI contrast agents for Zn2+ detection: towards rational design.

    PubMed

    Bonnet, Célia S; Caillé, Fabien; Pallier, Agnès; Morfin, Jean-François; Petoud, Stéphane; Suzenet, Franck; Tóth, Éva

    2014-08-25

    A series of novel pyridine-based Gd(3+) complexes have been prepared and studied as potential MRI contrast agents for Zn(2+) detection. By independent assessment of molecular parameters affecting relaxivity, we could interpret the relaxivity changes observed upon Zn(2+) binding in terms of variations of the rotational motion. PMID:25116889

  17. Dual-energy coronary angiography in pigs using a Gd contrast agent

    NASA Astrophysics Data System (ADS)

    Fiedler, Stefan; Elleaume, Helene; Le Duc, Geraldine; Nemoz, Christian; Brochard, Thierry; Renier, Michel; Bertrand, Bernard; Esteve, Francois; Le Bas, Jean-Francois; Suortti, Pekka; Thomlinson, William C.

    2000-04-01

    The European Synchrotron Radiation Facility Medical Research Beamline is now fully operational. One of the primary programs is the development of dual-energy transvenous coronary angiography for in vivo human research protocols. Previous work at this and other synchrotrons has been entirely devoted to the use of the dual-energy digital subtraction technique at the iodine k-absorption edge at 33.17 keV. The images are recorded in a line scan mode following venous injection of the contrast agent. Considerations of the patient dose, the dilution of the contrast agent in the pulmonary system and the arteries overlying the filled ventricles have limited the image quality. The ESRF facility was designed to allow dual- energy imaging at higher energies, for example at the gadolinium k-absorption edge at 50.24 keV. The advantages have been theoretically known for many years, with the higher energy promising higher image quality with less radiation dose. During the commissioning phase of the ESRF angiography program, the opportunity presented itself to image adult pigs in vivo with Gd contrast agent. This paper presents some initial results of the image quality in the Gd studies in comparison with iodine contrast agent studies, also carried out in adult pigs at the ESRF.

  18. Evaluation of a targeted nanobubble ultrasound contrast agent for potential tumor imaging

    NASA Astrophysics Data System (ADS)

    Li, Chunfang; Shen, Chunxu; Liu, Haijuan; Wu, Kaizhi; Zhou, Qibing; Ding, Mingyue

    2015-03-01

    Targeted nanobubbles have been reported to improve the contrast effect of ultrasound imaging due to the enhanced permeation and retention effects at tumor vascular leaks. In this work, the contrast enhancement abilities and the tumor targeting potential of a self-made VEGFR2-targeted nanobubble ultrasound contrast agent was evaluated in-vitro and in-vivo. Size distribution and zeta potential were assessed. Then the contrast-enhanced ultrasound imaging of the VEGFR2 targeted nanobubbles were evaluated with a custom-made experimental apparatus and in normal Wistar rats. Finally, the in-vivo tumor-targeting ability was evaluated on nude mice with subcutaneous tumor. The results showed that the target nanobubbles had uniform distribution with the average diameter of 208.1 nm, polydispersity index (PDI) of 0.411, and zeta potential of -13.21 mV. Significant contrast enhancement was observed in both in-vitro and in-vivo ultrasound imaging, demonstrating that the self-made target nanobubbles can enhance the contrast effect of ultrasound imaging efficiently. Targeted tumor imaging showed less promising result, due to the fact that the targeted nanobubbles arriving and permeating through tumor vessels were not many enough to produce significant enhancement. Future work will focus on exploring new imaging algorithm which is sensitive to targeted nanobubbles, so as to correctly detect the contrast agent, particularly at a low bubble concentration.

  19. Alk5 inhibition increases delivery of macromolecular and protein-bound contrast agents to tumors

    PubMed Central

    Daldrup-Link, Heike E.; Mohanty, Suchismita; Ansari, Celina; Lenkov, Olga; Shaw, Aubie; Ito, Ken; Hong, Su Hyun; Hoffmann, Matthias; Pisani, Laura; Boudreau, Nancy; Gambhir, Sanjiv Sam; Coussens, Lisa M.

    2016-01-01

    Limited transendothelial permeability across tumor microvessels represents a significant bottleneck in the development of tumor-specific diagnostic agents and theranostic drugs. Here, we show an approach to increase transendothelial permeability of macromolecular and nanoparticle-based contrast agents via inhibition of the type I TGF-β receptor, activin-like kinase 5 (Alk5), in tumors. Alk5 inhibition significantly increased tumor contrast agent delivery and enhancement on imaging studies, while healthy organs remained relatively unaffected. Imaging data correlated with significantly decreased tumor interstitial fluid pressure, while tumor vascular density remained unchanged. This immediately clinically translatable concept involving Alk5 inhibitor pretreatment prior to an imaging study could be leveraged for improved tumor delivery of macromolecular and nanoparticle-based imaging probes and, thereby, facilitate development of more sensitive imaging tests for cancer diagnosis, enhanced tumor characterization, and personalized, image-guided therapies. PMID:27182558

  20. Preparation of near-infrared-labeled targeted contrast agents for clinical translation

    NASA Astrophysics Data System (ADS)

    Olive, D. Michael

    2011-03-01

    Targeted fluorophore-labeled contrast agents are moving toward translation to human surgical use. To prepare for future clinical use, we examined the performance of potential ligands targeting the epidermal growth factor receptor, α5β3 integrins, and GLUT transporters for their suitability as directed contrast agents. Each agent was labeled with IRDye 800CW, and near-infrared dye with excitation/emission wavelengths of 789/805 nm, which we determined had favorable toxicity characteristics. The probe molecules examined consisted of Affibodies, nanobodies, peptides, and the sugar 2-deoxy-D-glucose. Each probe was tested for specific and non-specific binding in cell based assays. All probe types showed good performance in mouse models for detecting either spontaneous tumors or tumor xenografts in vivo. Each of the probes tested show promise for future human clinical studies.

  1. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging.

    PubMed

    D'Hollander, Antoine; Mathieu, Evelien; Jans, Hilde; Vande Velde, Greetje; Stakenborg, Tim; Van Dorpe, Pol; Himmelreich, Uwe; Lagae, Liesbet

    2016-01-01

    The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS), realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3). Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. PMID:27536107

  2. Small animal imaging platform for quantitative assessment of short-wave infrared-emitting contrast agents

    NASA Astrophysics Data System (ADS)

    Hu, Philip; Mingozzi, Marco; Higgins, Laura M.; Ganapathy, Vidya; Zevon, Margot; Riman, Richard E.; Roth, Charles M.; Moghe, Prabhas V.; Pierce, Mark C.

    2015-03-01

    We report the design, calibration, and testing of a pre-clinical small animal imaging platform for use with short-wave infrared (SWIR) emitting contrast agents. Unlike materials emitting at visible or near-infrared wavelengths, SWIR-emitting agents require detection systems with sensitivity in the 1-2 μm wavelength region, beyond the range of commercially available small animal imagers. We used a collimated 980 nm laser beam to excite rare-earth-doped NaYF4:Er,Yb nanocomposites, as an example of a SWIR emitting material under development for biomedical imaging applications. This beam was raster scanned across the animal, with fluorescence in the 1550 nm wavelength region detected by an InGaAs area camera. Background adjustment and intensity non-uniformity corrections were applied in software. The final SWIR fluorescence image was overlaid onto a standard white-light image for registration of contrast agent uptake with respect to anatomical features.

  3. Development of nanostars as a biocompatible tumor contrast agent: toward in vivo SERS imaging

    PubMed Central

    D’Hollander, Antoine; Mathieu, Evelien; Jans, Hilde; Vande Velde, Greetje; Stakenborg, Tim; Van Dorpe, Pol; Himmelreich, Uwe; Lagae, Liesbet

    2016-01-01

    The need for sensitive imaging techniques to detect tumor cells is an important issue in cancer diagnosis and therapy. Surface-enhanced Raman scattering (SERS), realized by chemisorption of compounds suitable for Raman spectroscopy onto gold nanoparticles, is a new method for detecting a tumor. As a proof of concept, we studied the use of biocompatible gold nanostars as sensitive SERS contrast agents targeting an ovarian cancer cell line (SKOV3). Due to a high intracellular uptake of gold nanostars after 6 hours of exposure, they could be detected and located with SERS. Using these nanostars for passive targeting after systemic injection in a xenograft mouse model, a detectable signal was measured in the tumor and liver in vivo. These signals were confirmed by ex vivo SERS measurements and darkfield microscopy. In this study, we established SERS nanostars as a highly sensitive contrast agent for tumor detection, which opens the potential for their use as a theranostic agent against cancer. PMID:27536107

  4. Stable Encapsulation of Air in Mesoporous Silica Nanoparticles: Fluorocarbon-Free Nanoscale Ultrasound Contrast Agents.

    PubMed

    Yildirim, Adem; Chattaraj, Rajarshi; Blum, Nicholas T; Goldscheitter, Galen M; Goodwin, Andrew P

    2016-06-01

    While gas-filled micrometer-sized ultrasound contrast agents vastly improve signal-to-noise ratios, microbubbles have short circulation lifetimes and poor extravasation from the blood. Previously reported fluorocarbon-based nanoscale contrast agents are more stable but their contrast is generally lower owing to their size and dispersity. The contrast agents reported here are composed of silica nanoparticles of ≈100 nm diameter that are filled with ≈3 nm columnar mesopores. Functionalization of the silica surface with octyl groups and resuspension with Pluronic F127 create particles with pores that remain filled with air but are stable in buffer and serum. Administration of high intensity focused ultrasound (HIFU) allows sensitive imaging of the silica nanoparticles down to 10(10) particles mL(-1) , with continuous imaging for at least 20 min. Control experiments with different silica particles supported the hypothesis that entrapped air could be pulled into bubble nuclei, which can then in turn act as acoustic scatterers. This process results in very little hemolysis in whole blood, indicating potential for nontoxic blood pool imaging. Finally, the particles are lyophilized and reconstituted or stored in PBS (phosphate-buffered saline, at least for four months) with no loss in contrast, indicating stability to storage and reformulation. PMID:26990167

  5. Comparison of the optoacoustic signal generation efficiency of different nanoparticular contrast agents.

    PubMed

    Bost, Wolfgang; Lemor, Robert; Fournelle, Marc

    2012-11-20

    Optoacoustic imaging represents a new modality that allows noninvasive in vivo molecular imaging with optical contrast and acoustical resolution. Whereas structural or functional imaging applications such as imaging of vasculature do not require contrast enhancing agents, nanoprobes with defined biochemical binding behavior are needed for molecular imaging tasks. Since the contrast of this modality is based on the local optical absorption coefficient, all particle or molecule types that show significant absorption cross sections in the spectral range of the laser wavelength used for signal generation are suitable contrast agents. Currently, several particle types such as gold nanospheres, nanoshells, nanorods, or polymer particles are used as optoacoustic contrast agents. These particles have specific advantages with respect to their absorption properties, or in terms of biologically relevant features (biodegradability, binding to molecular markers). In the present study, a comparative analysis of the signal generation efficiency of gold nanorods, polymeric particles, and magnetite particles using a 1064 nm Nd:YAG laser for signal generation is described. PMID:23207315

  6. Gadolinium-containing MRI contrast agents: important variations on a theme for NSF.

    PubMed

    Kuo, Phillip H

    2008-01-01

    Millions of doses of gadolinium-based contrast agents (GBCAs) are administered annually to improve the clinical utility of magnetic resonance imaging. All the approved agents incorporate one atom of the rare earth metal gadolinium into a chelate to improve the safety of the ordinarily toxic free gadolinium. The undeniable epidemiologic link between GBCAs and nephrogenic systemic fibrosis (NSF) has prompted renewed investigation into the different chemical properties of the GBCAs despite their clinical interchangeability. Gadolinium-based contrast agents can be divided into different categories: linear versus macrocyclic structure, ionic versus nonionic, and non-protein-binding versus protein-binding agents. The GBCAs differ significantly with respect to transmetallation and kinetic and thermodynamic stability and therefore their propensity to release free gadolinium, which is hypothesized to induce NSF. That gadodiamide, with its susceptibility to transmetallation and relatively low thermodynamic and kinetic stability, is associated with the most cases of NSF supports this hypothesis. On the other hand, the greater stability of a macrocyclic agent hypothetically would confer a greater safety margin with regard to NSF. Because few published data on an experimental model of NSF exist, continuing vigilance is necessary to report new cases of NSF, especially with regard to the agents with small market share. PMID:18180006

  7. Diagnosis of Popliteal Venous Entrapment Syndrome by Magnetic Resonance Imaging Using Blood-Pool Contrast Agents

    SciTech Connect

    Beitzke, Dietrich Wolf, Florian; Juelg, Gregor; Lammer, Johannes; Loewe, Christian

    2011-02-15

    Popliteal vascular entrapment syndrome is caused by aberrations or hypertrophy of the gastrocnemius muscles, which compress the neurovascular structures of the popliteal fossa, leading to symptoms of vascular and degeneration as well as aneurysm formation. Imaging of popliteal vascular entrapment may be performed with ultrasound, magnetic resonance imaging (MRI), computed tomography angiography, and conventional angiography. The use of blood-pool contrast agents in MRI when popliteal vascular entrapment is suspected offers the possibility to perform vascular imaging with first-pass magnetic resonance angiographic, high-resolution, steady-state imaging and allows functional tests all within one examination with a single dose of contrast agent. We present imaging findings in a case of symptomatic popliteal vein entrapment diagnosed by the use of blood pool contrast-enhanced MRI.

  8. Amphiphilic polymer-coated hybrid nanoparticles as CT/MRI dual contrast agents

    NASA Astrophysics Data System (ADS)

    Kim, Dongkyu; Yu, Mi Kyung; Lee, Tae Sup; Park, Jae Jun; Jeong, Yong Yeon; Jon, Sangyong

    2011-04-01

    We describe hybrid nanoparticles, composed of iron oxide and gold nanoparticles, as potential dual contrast agents for both computed tomography (CT) and magnetic resonance imaging (MRI). The hybrid nanoparticles are synthesized by thermal decomposition of mixtures of Fe-oleate and Au-oleylamine complexes. Using a nano-emulsion method, the nanoparticles are coated with amphiphilic poly(DMA-r-mPEGMA-r-MA) to impart water-dispersity and antibiofouling properties. An in vitro phantom study shows that the hybrid nanoparticles have high CT attenuation, because of the constituent gold nanoparticles, and afford a good MR signal, attributable to the contained iron oxide nanoparticles. Intravenous injection of the hybrid nanoparticles into hepatoma-bearing mice results in high contrast between the hepatoma and normal hepatic parenchyma in both CT and MRI. These results suggest that the hybrid nanoparticles may be useful as CT/MRI dual contrast agents for in vivo hepatoma imaging.

  9. Synthesis of nanoparticle CT contrast agents: in vitro and in vivo studies

    NASA Astrophysics Data System (ADS)

    Kim, Sung June; Xu, Wenlong; Wasi Ahmad, Md; Baeck, Jong Su; Chang, Yongmin; Bae, Ji Eun; Chae, Kwon Seok; Kim, Tae Jeong; Park, Ji Ae; Lee, Gang Ho

    2015-10-01

    Water-soluble and biocompatible D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles were synthesized for the first time to be used as x-ray computed tomography (CT) contrast agents. Their average particle diameters were 3.2 ± 0.1 and 2.8 ± 0.1 nm for D-glucuronic acid coated Na2WO4 and BaCO3 nanoparticles, respectively. All the nanoparticles exhibited a strong x-ray attenuation. In vivo CT images were obtained after intravenous injection of an aqueous sample suspension of D-glucuronic acid coated Na2WO4 nanoparticles, and positive contrast enhancements in the kidney were clearly shown. These findings indicate that the nanoparticles reported in this study may be promising CT contrast agents.

  10. Diagnostic and therapeutic research on ultrasound microbubble/nanobubble contrast agents (Review).

    PubMed

    Ma, Jing; Xu, Chang Song; Gao, Feng; Chen, Ming; Li, Fan; Du, Lian Fang

    2015-09-01

    The contrast enhanced imaging function of ultrasound contrast agents (UCAs) has been extensively investigated using physical acoustic signatures. It has a number of novel applications, including tissue‑specific molecular imaging and multi‑modal imaging. In addition there are numerous other therapeutic applications of UCAs, for example as vehicles for drug or gene delivery. These uses are discussed, as well as the acoustically‑induced biological effects, including ultrasound targeted microbubble destruction (UTMD). This review also explores the considerations for the safe use of UCA from an acoustic standpoint. The scope of the application of UCA has markedly expanded in recent years, and it is a rapidly growing field of medical research. The current article reviews recent advances in the diagnostic and therapeutic applications of ultrasound microbubble/nanobubble contrast agents. PMID:26081968