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Sample records for blood-pool contrast agent

  1. 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

  2. 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.

  3. 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

  4. Stability of echogenic liposomes as a blood pool ultrasound contrast agent in a physiologic flow phantom

    PubMed Central

    Radhakrishnan, Kirthi; Haworth, Kevin J.; Huang, Shao-Ling; Klegerman, Melvin E.; McPherson, David D.; Holland, Christy K.

    2016-01-01

    investigations will be needed to evaluate the optimal usage of ELIP as blood pool contrast agents. PMID:22929652

  5. Validation of Perfusion Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using a Blood Pool Contrast Agent in Skeletal Swine Muscle

    PubMed Central

    Hindel, Stefan; Sauerbrey, Anika; Maaß, Marc; Maderwald, Stefan; Schlamann, Marc; Lüdemann, Lutz

    2015-01-01

    The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the

  6. Validation of Perfusion Quantification with 3D Gradient Echo Dynamic Contrast-Enhanced Magnetic Resonance Imaging Using a Blood Pool Contrast Agent in Skeletal Swine Muscle.

    PubMed

    Hindel, Stefan; Sauerbrey, Anika; Maaß, Marc; Maderwald, Stefan; Schlamann, Marc; Lüdemann, Lutz

    2015-01-01

    The purpose of our study was to validate perfusion quantification in a low-perfused tissue by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) with shared k-space sampling using a blood pool contrast agent. Perfusion measurements were performed in a total of seven female pigs. An ultrasonic Doppler probe was attached to the right femoral artery to determine total flow in the hind leg musculature. The femoral artery was catheterized for continuous local administration of adenosine to increase blood flow up to four times the baseline level. Three different stable perfusion levels were induced. The MR protocol included a 3D gradient-echo sequence with a temporal resolution of approximately 1.5 seconds. Before each dynamic sequence, static MR images were acquired with flip angles of 5°, 10°, 20°, and 30°. Both static and dynamic images were used to generate relaxation rate and baseline magnetization maps with a flip angle method. 0.1 mL/kg body weight of blood pool contrast medium was injected via a central venous catheter at a flow rate of 5 mL/s. The right hind leg was segmented in 3D into medial, cranial, lateral, and pelvic thigh muscles, lower leg, bones, skin, and fat. The arterial input function (AIF) was measured in the aorta. Perfusion of the different anatomic regions was calculated using a one- and a two-compartment model with delay- and dispersion-corrected AIFs. The F-test for model comparison was used to decide whether to use the results of the one- or two-compartment model fit. Total flow was calculated by integrating volume-weighted perfusion values over the whole measured region. The resulting values of delay, dispersion, blood volume, mean transit time, and flow were all in physiologically and physically reasonable ranges. In 107 of 160 ROIs, the blood signal was separated, using a two-compartment model, into a capillary and an arteriolar signal contribution, decided by the F-test. Overall flow in hind leg muscles, as measured by the

  7. Synthesis, relaxation properties and in vivo assessment of a carborane-GdDOTA-monoamide conjugate as an MRI blood pool contrast agent.

    PubMed

    Goswami, Lalit N; Cai, Quanyu; Ma, Lixin; Jalisatgi, Satish S; Hawthorne, M Frederick

    2015-09-01

    The synthesis, relaxivity measurements and in vivo assessment of a carborane-GdDOTA-monoamide (CB-GdDOTA-MA) amphiphilic conjugate as a blood pool contrast agent (BPCA) is reported. This BPCA exhibited excellent binding (87.4%) with human serum albumin (HSA) and showed a higher relaxivity value (r1 = 6.8 mM(-1) s(-1), 7 T) as compared to the clinically used BPCA, MS-325 (r1 = 5.1 mM(-1) s(-1), 9.4 T) in PBS. The blood pool contrast enhancement (CE) capability of CB-GdDOTA-MA was evaluated by performing MR angiography (MRA) in CF1 mice (n = 4) at a Gd dose of 0.1 mmol per kg body weight. The significant CE of blood vessels persisted for about 3-4 min post-injection (p.i.) and quickly diminishes over time. The significant CE of the bladder for up to 3 h p.i. indicated that the renal system is the primary clearance pathway for CB-GdDOTA-MA. However, the CE of liver tissues and intestine (up to 24 h p.i.) is suggestive of a significant hepatic uptake of the CB-GdDOTA-MA. PMID:26204958

  8. Low toxicity and long circulation time of Polyampholyte-coated magnetic nanoparticles for blood pool contrast agents

    NASA Astrophysics Data System (ADS)

    Wang, Qi; Shen, Ming; Zhao, Tao; Xu, Yuanyuan; Lin, Jiang; Duan, Yourong; Gu, Hongchen

    2015-01-01

    Polyampholyte-coated (poly(acrylic acid) (PAA)-co-3-(diethylamino)-propylamine (DEAPA)) magnetite nanoparticles (PAMNPs) have been prepared as contrasting agent used in magnetic resonance imaging (MRI). Excellent biocompatibility is required for contrasting agents used in high-resolution magnetic resonance angiography. To evaluate the biocompatibility of PAMNPs, some experiments have been conducted. The hemolysis, plasma recalcification, dynamic blood clotting, prothrombin time, inflammatory cytokine release and complement system activation assays were carried out to investigate the hemocompatibility. To evaluate the toxicity to vessel, MTT test and vascular irritation tests were conducted. Tissue toxicity test was also performed to investigate the biocompability in vivo. We also looked into the biodistribution. The results showed that PAMNPs at the working concentration (0.138 mM) present similar hemocompatibility with negative control, thus have no significant effect to vessels. PAMNPs were mainly distributed in the liver and the blood. The circulation time in blood was considerably long, with the half-time of 3.77 h in plasma. This property is advantageous for PAMNPs' use in angiography. PAMNPs could be metabolized rapidly in mice and were not observed to cause any toxic or adverse effect. In short, these results suggest that the PAMNPs have great potential to serve as safe contrast agents in magnetic resonance imaging (MRI).

  9. Low toxicity and long circulation time of Polyampholyte-coated magnetic nanoparticles for blood pool contrast agents

    PubMed Central

    Wang, Qi; Shen, Ming; Zhao, Tao; Xu, Yuanyuan; Lin, Jiang; Duan, Yourong; Gu, Hongchen

    2015-01-01

    Polyampholyte-coated (poly(acrylic acid) (PAA)-co-3-(diethylamino)-propylamine (DEAPA)) magnetite nanoparticles (PAMNPs) have been prepared as contrasting agent used in magnetic resonance imaging (MRI). Excellent biocompatibility is required for contrasting agents used in high-resolution magnetic resonance angiography. To evaluate the biocompatibility of PAMNPs, some experiments have been conducted. The hemolysis, plasma recalcification, dynamic blood clotting, prothrombin time, inflammatory cytokine release and complement system activation assays were carried out to investigate the hemocompatibility. To evaluate the toxicity to vessel, MTT test and vascular irritation tests were conducted. Tissue toxicity test was also performed to investigate the biocompability in vivo. We also looked into the biodistribution. The results showed that PAMNPs at the working concentration (0.138 mM) present similar hemocompatibility with negative control, thus have no significant effect to vessels. PAMNPs were mainly distributed in the liver and the blood. The circulation time in blood was considerably long, with the half-time of 3.77 h in plasma. This property is advantageous for PAMNPs' use in angiography. PAMNPs could be metabolized rapidly in mice and were not observed to cause any toxic or adverse effect. In short, these results suggest that the PAMNPs have great potential to serve as safe contrast agents in magnetic resonance imaging (MRI). PMID:25585607

  10. Detection of Type II Endoleak After Endovascular Aortic Repair: Comparison Between Magnetic Resonance Angiography and Blood-Pool Contrast Agent and Dual-Phase Computed Tomography Angiography

    SciTech Connect

    Wieners, Gero; Meyer, Frank; Halloul, Zuhir; Peters, Nils; Ruehl, Ricarda; Dudeck, Oliver; Tautenhahn, Joerg; Ricke, Jens; Pech, Maciej

    2010-12-15

    PurposeThis prospective study was designed to assess the diagnostic value of magnetic resonance angiography (MRA) with blood-pool contrast agent (gadofosveset) in the detection of type-II endoleak after endovascular aortic repair (EVAR).MethodsThirty-two patients with aortic aneurysms who had undergone EVAR were included in this study. All patients were examined by dual-phase computed tomography angiography (CTA) as well as MRA with gadofosveset in the first-pass and steady-state phases. Two independent readers evaluated the images of CTA and MRA in terms of endoleak type II, feeding vessel, and image quality.ResultsMedian follow-up-time after EVAR was 22 months (range 4 to 59). Endoleak type II was detected by CTA in 12 of 32 patients (37.5%); MRA detected endoleak in all of these patients as well as in another 9 patients (n = 21, 65.6%), of whom the endoleaks in 6 patients showed an increasing diameter. Most endoleaks were detected in the steady-state phase (n = 14). The decrease in diameter of the aneurysmal sac was significantly greater in the patients without a visible endoleak that was visible on MRA (P = 0.004). In the overall estimation of diagnostic accuracy, MRA was judged superior to CTA in 66% of all examinations.ConclusionMRA with gadofosveset appeared superior to CTA, and has higher diagnostic accuracy, in the detection of endoleak after EVAR.

  11. Comparison of three dimensional magnetic resonance imaging in conjunction with a blood pool contrast agent and nuclear scintigraphy for the detection of experimentally induced gastrointestinal bleeding

    PubMed Central

    Hilfiker, P; Weishaupt, D; Kacl, G; Hetzer, F; Griff, M; Ruehm, S; Debatin, J

    1999-01-01

    BACKGROUND AND AIMS—To compare the performance of 3D magnetic resonance imaging (MRI) in conjunction with an intravascular contrast agent with that of scintigraphy, with respect to detection and localisation of gastrointestinal haemorrhage in vivo in pigs.
METHODS—Intraluminal bleeding sites were surgically created in the small bowel and colon of six pigs. The animals underwent scintigraphy with 99mTc labelled red blood cells and 3D MRI following administration of an intravascular contrast agent (NC100150) at five minute intervals over 30 minutes. For analysis, the intestinal tract was divided into six segments. Based on the two evaluated methods, each segment was characterised on a five point scale regarding the presence of a bleed. At autopsy, the surgically manipulated bowel segments were inspected for the presence of haemorrhage.
RESULTS—Bleeding was confirmed at autopsy in 18/36 segments. Contrast extravasation with subsequent movement through the bowel could be documented on MRI data sets. All segments were correctly characterised, resulting in 100% sensitivity and specificity for MRI. Based on scintigraphy, interpretation of seven segments (19%) was false (sensitivity/specificity of 78%/72%). Differences in diagnostic performance were evident in the receiver operator characteristic (ROC) analysis, with an area under the MRI curve of 0.99 and under the scintigraphy curve of 0.85.
CONCLUSION—In conjunction with an intravascular contrast agent, 3D MRI permits accurate detection and localisation of gastrointestinal bleeding. The extent and evolution of intestinal bleeding can be determined with repeated data acquisition.


Keywords: gastrointestinal tract; haemorrhage; scintigraphy; magnetic resonance; contrast agent PMID:10486369

  12. Detection of deep vein thrombosis: combined flow and blood pool radionuclide venography vs contrast venography.

    PubMed

    Caner, B; Ozmen, M; Dincer, A; Kapucu, O; Bekdik, C

    1991-10-01

    This study was performed to validate the combined study of flow radionuclide venography (FRV) with subsequent 99mTc-red blood cell(RBC) blood pool radionuclide venography(BRV) for the detection of deep vein thrombosis (DVT). Findings in 32 patients with suspected DVT of lower extremities (n = 52) were compared with those of corresponding contrast venograms (CV) serving as a reference method. FRV was performed by using three separate doses of a large 99mTc04-bolus (10-12 cc) injection. The findings were as follows: concerning the detection of DVT in calf veins, agreement between FRV and CV, FRV+BRV and CV, and BRV and CV were 67%, 73% and 60%, respectively. For femoral veins, agreement between FRV and CV was 96%, while it was 87% between BRV and CV. When FRV and BRV of femoral veins were evaluated in combination, 100% agreement between radionuclide and radiologic method was observed. For iliac veins there was no disagreement in comparison of the methods either singly or in combination. In 7.6% of the extremities, collaterals not demonstrated by CV and BRV were visualized only by FRV. Although the radioactive agent was injected in a relatively large volume, all of the calf veins could not be filled even when they were completely patent. It was concluded that a combined study of FRV with BRV improved the diagnostic value of radionuclide venography for the detection of DVT in calf and femoral veins. PMID:1659257

  13. Tc-99m dextran: a new blood-pool-labeling agent for radionuclide angiocardiography

    SciTech Connect

    Henze, E.; Robinson, G.D.; Kuhl, D.E.; Schelbert, H.R.

    1982-04-01

    We have explored the possibility of imaging the cadiac blood pool with dextran (Dx) labeled with Tc-99m (Tc) after Sn/sup 2 +/ reduction. Stannous dextrane (SnDx) kits were prepared in advance and labeling was performed by adding Tc-99m. The labeling efficiency was greater than 95%. Technetium-99m dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights ( 4 x 10/sup 4/ = Dx-40; 5 x 10/sup 5/ = Dx-500; 1 x 10/sup 6/ = Dx-2000) and with Tc-99m red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.

  14. /sup 99m/Tc dextran: a new blood-pool-labeling agent for radionuclide angiocardiography

    SciTech Connect

    Henze, E.; Robinson, G.D.; Kuhl, D.E.; Schelbert, H.R.

    1982-04-01

    We have explored the possibility of imaging the cardiac blood pool with dextran (Dx) labeled with /sup 99m/Tc (Tc) after Sn2+ reduction. Stannous dextran (SnDx) kits were prepared in advance and labeling was performed by adding /sup 99m/Tc. The labeling efficiency was greater than 95%. /sup 99m/Tc dextran (TcDx) was highly stable both in vivo and in vitro. In seven dogs we compared the quality of blood-pool images obtained with TcDx of different molecular weights (4 X 10(4) . Dx-40; 5 X 10(5) . Dx-500; 2 X 10(6) . Dx-2000) and with /sup 99m/Tc red blood cells (TcRBC) labeled in vitro, and determined the organ distribution of this new agent by whole-body scanning and blood sampling. TcDx provided high-quality cardiac blood-pool images up to 60 min after injection. The heart-to-lung ratios averaged 3.7 for TcDx-40, 3.9 for TcDx-500, and 5.4 for TcRBC at 60 min. Whereas TcDx-40 showed a relatively rapid initial urinary excretion and TcDx-2000 was degraded rapidly, TcDx-500 demonstrated the best kinetics for blood-pool imaging. Thus, TcDx is a new radiopharmaceutical with high labeling efficiency and stability. It overcomes a number of the limitations of currently used blood-labeling agents and may become useful for blood-pool imaging in man.

  15. Pulmonary Hemorrhage: Imaging with a New Magnetic Resonance Blood Pool Agent in Conjunction with Breathheld Three-Dimensional Magnetic Resonance Angiography

    SciTech Connect

    Weishaupt, Dominik; Hilfiker, Paul R.; Schmidt, Michaela; Debatin, Joerg F.

    1999-07-15

    Purpose: To describe the three-dimensional magnetic resonance angiography (3D MRA) imaging appearance of the pulmonary arteries following administration of a superparamagnetic iron oxide blood pool agent to human volunteers, and to demonstrate in an animal model (pigs) how this technique can be used to detect pulmonary parenchymal hemorrhage. Methods: Two volunteers were examined following the intravenous administration of a superparamagnetic iron oxide blood pool agent (NC100150 Injection, Nycomed Amersham Imaging, Wayne, PA, USA). T1-weighted 3D gradient recalled echo (GRE) image sets (TR/TE 5.1/1.4 msec, flip angle 30 deg.) were acquired breathheld over 24 sec. To assess the detectability of pulmonary bleeding with intravascular MR contrast, pulmonary parenchymal injuries were created in two animals under general anesthesia, and fast T1-weighted 3D GRE image sets collected before and after the injury. Results: Administration of the intravascular contrast in the two volunteers resulted in selective enhancement of the pulmonary vasculature permitting complete visualization and excellent delineation of central, segmental, and subsegmental arteries. Following iatrogenic injury in the two animals, pulmonary hemorrhage was readily detected on the 3D image sets. Conclusion: The data presented illustrate that ultrafast 3D GRE MR imaging in conjunction with an intravenously administered intravascular blood pool agent can be used to perform high-quality pulmonary MRA as well as to detect pulmonary hemorrhage.

  16. Nano Liposomes Labeled with 99mTc-HMPAO, a Novel Agent for Blood Pool Imaging

    PubMed Central

    Sadri, Kayvan; Momenypoor, Salimeh; Dabbagh Kakhki, Vahid Reza; Sadeghi, Ramin; Aryana, Kamran; Johari Daha, Fariba; Zakavi, Seyed Rasoul; Jaafari, Mahmoud Reza

    2015-01-01

    In-vitro labeling of RBC with 99mTc is an intricate procedure and there is always a need for an alternate blood pool imaging agent. The aim of this study was to prepare an effective nano sized liposome (NLs) similar to human RBC for blood pool scintigraphy. This study formulates PEG-NLs and non-PEG-NLs using film method plus high pressure homogenization technique. Biodistribution studies were performed on BALB/C mice 1, 4 and 24 h after tail vein injection of labeled NLs with 99mTc hexamethylpropylene-amine-oxime (99mTc-HMPAO). Planar images were acquired using a 256 × 256 matrix following99m Tc-HMPAO-NLs injection into ear vein of rabbits 1, 2 and 24 h later. SPECT images were obtained 15 minutes after the injection (64 slices, 30 second/projection). The mean diameter, zeta potential and polydispersity index (PDI) of the PEG-NLs and the NLs were (80.88 ± 0.594 nm, -12.5 ± 0.56 mv, 0.158 ± 0.025) and (94.14 ± 0.114 nm, -35.5 ± 0.67 mv and 0.198 ± 0.007), respectively. 99mTc-HMPAO-PEG-NLs showed a significant circulation tracer activity (7.74 ± 1.63%ID/g at 1 h and 4.9 ± 0.77 %ID/g at 4 h), with low liver accumulation (12.07 ± 3.66 %ID/g at 1 h and 14.85 ± 1.3 %ID/g at 4 h). Heart to liver, spleen and background ROIs (region of interests) for 99m Tc-HMPAO-PEG-NLs were 1.25, 4 and 4.28 respectively at 2 h which changed to 1.06, 1.75 and 2.51 respectively at 24 h. The 99mTc-HMPAO-PEG-NLs with a prolonged blood circulation time could be an excellent RBC alternative for scintigraphy and gastrointestinal bleeding. PMID:26664365

  17. Functional Flow Patterns and Static Blood Pooling in Tumors Revealed by Combined Contrast-Enhanced Ultrasound and Photoacoustic Imaging.

    PubMed

    Bar-Zion, Avinoam; Yin, Melissa; Adam, Dan; Foster, F Stuart

    2016-08-01

    Alterations in tumor perfusion and microenvironment have been shown to be associated with aggressive cancer phenotypes, raising the need for noninvasive methods of tracking these changes. Dynamic contrast-enhanced ultrasound (DCEUS) and photoacoustic (PA) imaging serve as promising candidates-one has the ability to measure tissue perfusion, whereas the other can be used to monitor tissue oxygenation and hemoglobin concentration. In this study, we investigated the relationship between the different functional parameters measured with DCEUS and PA imaging, using two morphologically different hind-limb tumor models and drug-induced alterations in an orthotopic breast tumor model. Imaging results showed some correlation between perfusion and oxygen saturation maps and the ability to sensitively monitor antivascular treatment. In addition, DCEUS measurements revealed different vascular densities in the core of specific tumors compared with their rims. Noncorrelated perfusion and hemoglobin concentration measurements facilitated discrimination between blood lakes and necrotic areas. Taken together, our results illustrate the utility of a combined contrast-enhanced ultrasound method with photoacoustic imaging to visualize blood flow patterns in tumors. Cancer Res; 76(15); 4320-31. ©2016 AACR. PMID:27325651

  18. Dendrimer-entrapped gold nanoparticles as potential CT contrast agents for blood pool imaging

    PubMed Central

    2012-01-01

    The purpose of this study was to evaluate dendrimer-entrapped gold nanoparticles [Au DENPs] as a molecular imaging [MI] probe for computed tomography [CT]. Au DENPs were prepared by complexing AuCl4- ions with amine-terminated generation 5 poly(amidoamine) [G5.NH2] dendrimers. Resulting particles were sized using transmission electron microscopy. Serial dilutions (0.001 to 0.1 M) of either Au DENPs or iohexol were scanned by CT in vitro. Based on these results, Au DENPs were injected into mice, either subcutaneously (10 μL, 0.007 to 0.02 M) or intravenously (300 μL, 0.2 M), after which the mice were imaged by micro-CT or a standard mammography unit. Au DENPs prepared using G5.NH2 dendrimers as templates are quite uniform and have a size range of 2 to 4 nm. At Au concentrations above 0.01 M, the CT value of Au DENPs was higher than that of iohexol. A 10-μL subcutaneous dose of Au DENPs with [Au] ≥ 0.009 M could be detected by micro-CT. The vascular system could be imaged 5 and 20 min after injection of Au DENPs into the tail vein, and the urinary system could be imaged after 60 min. At comparable time points, the vascular system could not be imaged using iohexol, and the urinary system was imaged only indistinctly. Findings from this study suggested that Au DENPs prepared using G5.NH2 dendrimers as templates have good X-ray attenuation and a substantial circulation time. As their abundant surface amine groups have the ability to bind to a range of biological molecules, Au DENPs have the potential to be a useful MI probe for CT. PMID:22429280

  19. 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

  20. 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

  1. 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

  2. Hemophilic bleeding evaluated by blood pool scanning.

    PubMed

    Green, D; Spies, S M; Rana, N A; Milgram, J W; Mintzer, R

    1981-06-30

    The technique of blood pool scanning was used to examine 15 hemophilic subjects. Employing an in vivo method for erythrocyte labeling with Technetium-99 m, a dynamic perfusion sequence is obtained using a scintillation camera positioned over the area to be examined. This demonstrates the vascularity of the tissue. Subsequently, equilibrium blood pool images of the area are obtained and analyzed with a densitometer to assess relative regional blood volume. In patients who were not bleeding but had chronic arthropathy, vascularity was not increased, and the blood volume of comparable joints was similar. By contrast, marked increases in vascularity and image density were observed in studies of acutely bleeding joints. Chronic hemarthroses were associated with persistent, but less marked increases in joint perfusion. Transient increases in joint vascularity were demonstrated after insertion of knee prostheses. In a patient with a thigh hematoma, the dimensions of the hemorrhage were clearly delineated. Since only a tracer dose of nuclide is infused intravenously, there are no allergic reactions or other side effects of the procedure. Blood pool scanning is a safe, non-invasive technique that augments clinical and radiographic evaluations, and provides a new dimension in the assessment of the hemophilic patient. PMID:6269248

  3. 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

  4. 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.

  5. Preparation and radiochemical control of 99mTc labeled blood pool agent for in vivo labelling of the red blood cells.

    PubMed

    Ahmad, Israr; Amir, Noshad; Durr-E-Sabih; Bin Asad, Muhammad Hassham Hassan; Rahim, Muhammad Kashif; Hussain, Muhammad Shahzad; Murtaza, Ghulam; Shah, Syed Nisar Hussaian

    2014-01-01

    Our aim was to prepare cheap blood pool imaging kits by simplified method to overcome the burden on purchase department of MINAR, Nishtar Hospital, Multan, Pakistan. Secondarily, prompt supply of kits should save the time of patient during transportation. A total of 24 subjects selected for this study were equally divided into two groups. Mixture of stannous chloride and sodium pyrophosphate solution at pH 7 was injected to these subjects. Various concentrations (ranging from 200 to 800 microg) of stannous chloride dihydrate were injected to group one, followed by intravenous administration of technetium-99m (99mTc) pertechnetate at 30 min interval in 12 subjects. Labeling percentage of each sample was calculated afterwards followed by imaging under gamma camera. Each parameter was tested on three different patients and average of these three was calculated. In second set of experiments done on group two the same procedure was repeated in another 12 subjects, while keeping the concentration of Sn PYP constant at 400 microg. In this case, 99mTc was administered at different time intervals in different subjects ranging from 15 to 120 min (15, 30, 60 and 120 min) followed by calculation of labeling percentage and imaging under gamma camera. In group one, average percentage values of binding of red blood cells with 99mTc were 23.24, 84.88, 83.78 and 60.33% for concentrations of 200, 400, 600 and 800 microg, respectively. In group two, average percentage binging values of 22.26, 84.36. 55.54 and 28.67% were calculated at time intervals of 15, 30, 60 and 120 min, respectively. It is concluded from the results that the best blood pool imaging under gamma camera was observed for the concentration of 400 microg and the time interval of 30 min. The maximum percentage binding of red blood cells with 99mTc was calculated at concentration of 400 microg after 30 min interval that also correlated with imaging results. PMID:25272643

  6. 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.

  7. 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.

  8. Ultra High-Resolution In vivo Computed Tomography Imaging of Mouse Cerebrovasculature Using a Long Circulating Blood Pool Contrast Agent

    PubMed Central

    Starosolski, Zbigniew; Villamizar, Carlos A.; Rendon, David; Paldino, Michael J.; Milewicz, Dianna M.; Ghaghada, Ketan B.; Annapragada, Ananth V.

    2015-01-01

    Abnormalities in the cerebrovascular system play a central role in many neurologic diseases. The on-going expansion of rodent models of human cerebrovascular diseases and the need to use these models to understand disease progression and treatment has amplified the need for reproducible non-invasive imaging methods for high-resolution visualization of the complete cerebral vasculature. In this study, we present methods for in vivo high-resolution (19 μm isotropic) computed tomography imaging of complete mouse brain vasculature. This technique enabled 3D visualization of large cerebrovascular networks, including the Circle of Willis. Blood vessels as small as 40 μm were clearly delineated. ACTA2 mutations in humans cause cerebrovascular defects, including abnormally straightened arteries and a moyamoya-like arteriopathy characterized by bilateral narrowing of the internal carotid artery and stenosis of many large arteries. In vivo imaging studies performed in a mouse model of Acta2 mutations demonstrated the utility of this method for studying vascular morphometric changes that are practically impossible to identify using current histological methods. Specifically, the technique demonstrated changes in the width of the Circle of Willis, straightening of cerebral arteries and arterial stenoses. We believe the use of imaging methods described here will contribute substantially to the study of rodent cerebrovasculature. PMID:25985192

  9. 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

  10. 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

  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. 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

  13. 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

  14. Ultrastable polyethyleneimine-stabilized gold nanoparticles modified with polyethylene glycol for blood pool, lymph node and tumor CT imaging.

    PubMed

    Zhang, Yongxing; Wen, Shihui; Zhao, Lingzhou; Li, Du; Liu, Changcun; Jiang, Wenbin; Gao, Xiang; Gu, Wentao; Ma, Nan; Zhao, Jinhua; Shi, Xiangyang; Zhao, Qinghua

    2016-03-14

    Development of new long-circulating contrast agents for computed tomography (CT) imaging of different biological systems still remains a great challenge. Here, we report the design and synthesis of branched polyethyleneimine (PEI)-stabilized gold nanoparticles (Au PSNPs) modified with polyethylene glycol (PEG) for blood pool, lymph node, and tumor CT imaging. In this study, thiolated PEI was first synthesized and used as a stabilizing agent to form AuNPs. The formed Au PSNPs were then grafted with PEG monomethyl ether via PEI amine-enabled conjugation chemistry, followed by acetylation of the remaining PEI surface amines. The formed PEGylated Au PSNPs were characterized via different methods. We show that the PEGylated Au PSNPs with an Au core size of 5.1 nm have a relatively long half-decay time (7.8 h), and display a better X-ray attenuation property than conventionally used iodine-based CT contrast agents (e.g., Omnipaque), and are hemocompatible and cytocompatible in a given concentration range. These properties of the Au PSNPs afford their uses as a contrast agent for effective CT imaging of the blood pool and major organs of rats, lymph node of rabbits, and the xenografted tumor model of mice. Importantly, the PEGylated Au PSNPs could be excreted out of the body with time and also showed excellent in vivo stability. These findings suggest that the formed PEGylated Au PSNPs may be used as a promising contrast agent for CT imaging of different biological systems. PMID:26890691

  15. Synthetic copolymer kit for radionuclide blood-pool imaging

    SciTech Connect

    Bogdanov, A.A. Jr.; Callahan, R.J.; Wilkinson, R.A.

    1994-11-01

    A synthetic blood pool imaging agent labeled with {sup 99m}Tc is reported. The agent, methoxypolyethylene glycolpoly-L-Iysyl-diethylenetriaminepentaacetate monoamide was synthesized from a covalent graft copolymer of methoxypolyethylene glycol succinate (molecular weight 5.1 kD) with subsequent modification of the product with diethylenetriamineacetyl residues. The polymer was formulated into a kit that contained Sn(II) and sodium acetate for radiolabeling with {sup 99m}Tc. Biodistribution studies were performed in rats. Blood-pool imaging and blood clearance determination was carried out in rabbits and in a rhesus monkey. The {sup 99m}Tc-labeled agent [specific activity greater than 3.7 GBq/mg; radiochemical purity more than 98% by thin-layer and high-performance liquid chromatography (HPLC)] demonstrated remarkable stability in solution (pH 5.5-6.5) with no radioactive products of degradation detectable by HPLC even at 24 hr postlabeling. The agent exhibited prolonged circulation in the blood with a half-life of 31.5 hr in rabbits. Bio-distribution in rats showed a lack of substantial accumulation of the agent in the reticuloendothelial system. Sequential acquisitions were performed in a rhesus monkey. The {sup 99m}Tc-labeled polymer kit was compared with the {sup 99m}Tc-red blood cells (RBCs) labeled in vitro. Both methods produced similar heart-to-lung ratios. The ratios remained essentially unchanged for up to 15 hr postinjection. The {sup 99m}Tc-labeled methaxypolyethylene glycol-poly-L-lysyl-diethylenetriamine pentaacetate monoamide is an attractive alternative to radiolabeled RBCs for blood pool imaging applications. 33 refs., 7 figs.

  16. Modern Perforator Flap Imaging with High-Resolution Blood Pool MR Angiography.

    PubMed

    Kagen, Alexander C; Hossain, Rydhwana; Dayan, Erez; Maddula, Soumya; Samson, William; Dayan, Joseph; Smith, Mark L

    2015-01-01

    Advances in microsurgical techniques have improved autologous reconstructions by providing new donor site options while decreasing donor site morbidity. Various preoperative imaging modalities have been studied to assess the relevant vascular anatomic structures, with magnetic resonance (MR) angiography traditionally lagging behind computed tomography (CT) with respect to spatial resolution. Blood pool MR angiography with gadofosveset trisodium, a gadolinium-based contrast agent with extended intravascular retention, has allowed longer multiplanar acquisitions with resultant voxel sizes similar to or smaller than those of CT and with improved signal-to-noise ratio and soft-tissue contrast while maintaining the ability to depict flow with time-resolved imaging. The resultant vascular detail enables precise evaluation of the relevant vascular anatomic structures, including the vessel course, size, and branching pattern, as well as the venous arborization pattern. In addition, any architectural distortion, vessel alteration, or injury from prior surgery can be depicted. The reporting radiologist should be aware of pertinent and incidental findings relevant to the planned surgery and the patient's disease so that he or she can assist the microsurgeon in flap design as a member of the multidisciplinary team. Given the lack of ionizing radiation exposure in patients who often have an elevated body mass index, high-spatial-resolution blood pool MR angiography has become the imaging reference standard for the preoperative assessment of perforator flap vascular and soft-tissue morphology in our practice. PMID:25884098

  17. Perfluorooctyl bromide traces self-assembled with polymeric nanovesicles for blood pool ultrasound imaging.

    PubMed

    Li, Hao; Wang, Ping; Wang, Xuan; Yin, Tinghui; Zhou, Guofu; Shuai, Xintao; Zheng, Rongqin

    2016-06-24

    A novel perfluorooctyl bromide (PFOB)-loaded nanovesicle with a size of about 500 nm was prepared by self-assembly of an amphiphilic block copolymer, poly(ethylene oxide)-b-poly(d,l-lactic acid) (PEG-PDLLA), for blood pool ultrasound imaging. The excellent compatibility of PFOB with the hydrophobic PDLLA block makes PFOB uniformly distribute and integrate well within the nanovesicle shell. In theory, both the compressibility and shell density of the nanovesicle as ultrasound scatterers are enhanced, resulting in much higher echo intensity compared to the other PFOB nanoparticles. In vitro and in vivo imaging results illustrate that these polymeric nanovesicles with extremely low content of PFOB show quite a good contrast-enhancing effect even if highly diluted in blood. Therefore this PFOB-loaded polymeric nanovesicle is anticipated to be applicable as an ultrasound contrast agent for normal angiography and specific imaging of capillary-abundant organs or tissues (e.g. tumors). PMID:27121357

  18. Crimson carrier, a long-acting contrast agent for in vivo near-infrared imaging of injured and diseased muscle.

    PubMed

    Prajapati, Suresh I; Martinez, Carlo O; Abraham, Jinu; McCleish, Amanda T; Michalek, Joel E; McManus, Linda M; Rubin, Brian P; Shireman, Paula K; Keller, Charles

    2010-08-01

    The near-infrared wavelengths (700-900 nm) are the most suitable optical window for light penetration and deep tissue imaging in small animals. Herein we report a near-infrared fluorescent contrast agent, crimson carrier, which acts as a blood pool contrast agent to detect and quantify injury and disease in live animals. After determining the excitation-emission spectra and pharmacokinetics, crimson carrier was injected into myoinjured mice to monitor their recovery. Crimson carrier was also used to image transgenic mice with spontaneous tumors. Crimson carrier has maximal excitation and emission wavelengths of 745 nm and 820 nm, respectively. Elimination occurs predominantly via urinary excretion. We demonstrate the utility of this contrast agent for serial imaging of traumatized muscle as well as muscle tumors. The unique long-acting pharmacokinetics and urinary excretion route characteristics make crimson carrier a contrast agent of choice for the visualization of tumors and injured muscle or other tissues in live animal studies. PMID:20544935

  19. A neutral polydisulfide containing Gd(III) DOTA monoamide as a redox-sensitive biodegradable macromolecular MRI contrast agent.

    PubMed

    Ye, Zhen; Zhou, Zhuxian; Ayat, Nadia; Wu, Xueming; Jin, Erlei; Shi, Xiaoyue; Lu, Zheng-Rong

    2016-01-01

    This work aims to develop safe and effective gadolinium (III)-based biodegradable macromolecular MRI contrast agents for blood pool and cancer imaging. A neutral polydisulfide containing macrocyclic Gd-DOTA monoamide (GOLS) was synthesized and characterized. In addition to studying the in vitro degradation of GOLS, its kinetic stability was also investigated in an in vivo model. The efficacy of GOLS for contrast-enhanced MRI was examined with female BALB/c mice bearing 4T1 breast cancer xenografts. The pharmacokinetics, biodistribution, and metabolism of GOLS were also determined in mice. GOLS has an apparent molecular weight of 23.0 kDa with T1 relaxivities of 7.20 mM(-1) s(-1) per Gd at 1.5 T, and 6.62 mM(-1) s(-1) at 7.0 T. GOLS had high kinetic inertness against transmetallation with Zn(2+) ions, and its polymer backbone was readily cleaved by L-cysteine. The agent showed improved efficacy for blood pool and tumor MR imaging. The structural effect on biodistribution and in vivo chelation stability was assessed by comparing GOLS with Gd(HP-DO3A), a negatively charged polydisulfide containing Gd-DOTA monoamide GODC, and a polydisulfide containing Gd-DTPA-bisamide (GDCC). GOLS showed high in vivo chelation stability and minimal tissue deposition of gadolinium. The biodegradable macromolecular contrast agent GOLS is a promising polymeric contrast agent for clinical MR cardiovascular imaging and cancer imaging. PMID:26218648

  20. Iodinated α-tocopherol nano-emulsions as non-toxic contrast agents for preclinical X-ray imaging.

    PubMed

    Li, Xiang; Anton, Nicolas; Zuber, Guy; Zhao, Minjie; Messaddeq, Nadia; Hallouard, François; Fessi, Hatem; Vandamme, Thierry F

    2013-01-01

    Micro-computed tomography (micro-CT) is an emerging imaging modality, due to the low cost of the imagers as well as their efficiency in establishing high-resolution (1-100 μm) three-dimensional images of small laboratory animals and facilitating rapid, structural and functional in vivo visualization. However use of a contrast agent is absolutely necessary when imaging soft tissues. The main limitation of micro-CT is the low efficiency and toxicity of the commercially available blood pool contrast agents. This study proposes new, efficient and non-toxic contrast agents for micro-CT imaging. This formulation consists of iodinated vitamin E (α-tocopheryl 2,3,5-triiodobenzoate) as an oily phase, formulated as liquid nano-emulsion droplets (by low-energy nano-emulsification), surrounded by a hairy PEG layer to confer stealth properties. The originality and strength of these new contrast agents lie not only in their outstanding contrasting properties, biocompatibility and low toxicity, but also in the simplicity of their fabrication: one-step synthesis of highly iodinated oil (iodine constitutes 41.7% of the oil molecule weight) and its spontaneous emulsification. After i.v. administration in mice (8.5% of blood volume), the product shows stealth properties towards the immune system and thus acts as an efficient blood pool contrast agent (t(1/2) = 9.0 h), exhibiting blood clearance following mono-exponential decay. A gradual accumulation predominantly due to hepatocyte uptake is observed and measured in the liver, establishing a strong hepatic contrast, persistent for more than four months. To summarize, in the current range of available or developed contrast agents for preclinical X-ray imaging, this agent appears to be one of the most efficient. PMID:23083930

  1. "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

  2. 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

  3. Ultrastable polyethyleneimine-stabilized gold nanoparticles modified with polyethylene glycol for blood pool, lymph node and tumor CT imaging

    NASA Astrophysics Data System (ADS)

    Zhang, Yongxing; Wen, Shihui; Zhao, Lingzhou; Li, Du; Liu, Changcun; Jiang, Wenbin; Gao, Xiang; Gu, Wentao; Ma, Nan; Zhao, Jinhua; Shi, Xiangyang; Zhao, Qinghua

    2016-03-01

    Development of new long-circulating contrast agents for computed tomography (CT) imaging of different biological systems still remains a great challenge. Here, we report the design and synthesis of branched polyethyleneimine (PEI)-stabilized gold nanoparticles (Au PSNPs) modified with polyethylene glycol (PEG) for blood pool, lymph node, and tumor CT imaging. In this study, thiolated PEI was first synthesized and used as a stabilizing agent to form AuNPs. The formed Au PSNPs were then grafted with PEG monomethyl ether via PEI amine-enabled conjugation chemistry, followed by acetylation of the remaining PEI surface amines. The formed PEGylated Au PSNPs were characterized via different methods. We show that the PEGylated Au PSNPs with an Au core size of 5.1 nm have a relatively long half-decay time (7.8 h), and display a better X-ray attenuation property than conventionally used iodine-based CT contrast agents (e.g., Omnipaque), and are hemocompatible and cytocompatible in a given concentration range. These properties of the Au PSNPs afford their uses as a contrast agent for effective CT imaging of the blood pool and major organs of rats, lymph node of rabbits, and the xenografted tumor model of mice. Importantly, the PEGylated Au PSNPs could be excreted out of the body with time and also showed excellent in vivo stability. These findings suggest that the formed PEGylated Au PSNPs may be used as a promising contrast agent for CT imaging of different biological systems.Development of new long-circulating contrast agents for computed tomography (CT) imaging of different biological systems still remains a great challenge. Here, we report the design and synthesis of branched polyethyleneimine (PEI)-stabilized gold nanoparticles (Au PSNPs) modified with polyethylene glycol (PEG) for blood pool, lymph node, and tumor CT imaging. In this study, thiolated PEI was first synthesized and used as a stabilizing agent to form AuNPs. The formed Au PSNPs were then grafted with PEG

  4. 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

  5. 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

  6. 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

  7. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents.

    PubMed

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors. PMID:23208215

  8. Detection of brain tumors using fluorescence diffuse optical tomography and nanoparticles as contrast agents

    NASA Astrophysics Data System (ADS)

    Fortin, Pierre-Yves; Genevois, Coralie; Koenig, Anne; Heinrich, Emilie; Texier, Isabelle; Couillaud, Franck

    2012-12-01

    Near-infrared fluorescence-enhanced diffuse optical tomography (fDOT) is used to localize tumors in mice using fluorescent nanoparticles as a blood pool contrast agent. The infrared dye DiR is loaded in the lipid core of nontargeted nanoparticles (DiR-lipidots) and injected systemically via the tail vein in mice bearing U87 tumors. Distribution and time-course of DiR-lipidots are followed using in vivo fluorescence reflectance imaging and reveal enhanced fluorescent signal within the subcutaneous tumors up to seven days due to the enhanced permeability and retention effect. Tumor growth into the brain is followed using bioluminescent imaging, and tumor localization is further determined by magnetic resonance imaging. The fDOT provides three-dimensional fluorescent maps that allow for consistent localization for both subcutaneous and brain tumors.

  9. 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.

  10. Synthesis and characterization of new low-molecular-weight lysine-conjugated Gd-DTPA contrast agents.

    PubMed

    Laurent, Sophie; Burtea, Carmen; Vander Elst, Luce; Muller, Robert N

    2011-01-01

    Various blood pool contrast agents (CAs), characterized by intravascular distribution, have been developed to assist contrast enhanced magnetic resonance angiography (MRA). Among these CAs, the DTPA derivatives conjugated to synthetic polypeptides, such as polylysine, represent attractive candidates for blood pool imaging. However, due to the presence of charged residues located on their backbone, these agents are retained in the kidneys and this compromises their long blood half-life. In order to overcome this major drawback of the polylysine compounds, two new low-molecular-weight CAs were synthesized in the present work by conjugating four or six 1-p-isothiocyanatobenzyl-DTPA moieties to tri- or penta-Lys peptides [(Gd-DTPA)(4) Lys(3) and (Gd-DTPA)(6) Lys(5)], respectively. All the -NH(2) groups of Lys were thus blocked by covalent conjugation to DTPA. The stability and relaxometric properties of these compounds, as well as their pharmacokinetic and biodistribution characteristics, were then evaluated. The half-life in blood of these new polylysine derivatives, as determined in rats, is twofold longer than that of Gd-DTPA. The compounds could thus be optimal blood pool markers for MRA, which typically uses fast acquisition times. The absence of positive molecular charge did not limit their retention in kidneys 2 h after administration. On the other hand, (Gd-DTPA)(4) Lys(3) is retained in kidneys to a lesser extent than (Gd-DTPA)(6) Lys(5) . Their moderate retention in blood and their higher stability and relaxivity in comparison with Gd-DTPA highlight these polylysine derivatives as optimal compared with previously developed polylysine compounds. PMID:21861283

  11. 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

  12. 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

  13. Synthesis and characterization of PEGylated polyethylenimine-entrapped gold nanoparticles for blood pool and tumor CT imaging.

    PubMed

    Zhou, Benqing; Zheng, Linfeng; Peng, Chen; Li, Du; Li, Jingchao; Wen, Shihui; Shen, Mingwu; Zhang, Guixiang; Shi, Xiangyang

    2014-10-01

    The synthesis and characterization of gold nanoparticles (AuNPs) entrapped within polyethylene glycol (PEG)-modified polyethylenimine (PEI) for blood pool and tumor computed tomography (CT) imaging are reported. In this approach, partially PEGylated PEI was used as a template for AuNP synthesis, followed by acetylating the PEI remaining surface amines. The synthesized PEGylated PEI-entrapped AuNPs (Au PENPs) were characterized via different methods. Our results reveal that the synthesized Au PENPs can be tuned to have an Au core size in a range of 1.9-4.6 nm and to be water-soluble, stable, and noncytotoxic in a studied concentration range. With a demonstrated better X-ray attenuation property than that of clinically used iodinated small molecular contrast agent (e.g., Omnipaque) and the prolonged half-decay time (11.2 h in rat) confirmed by pharmacokinetics studies, the developed PEGylated Au PENPs enabled efficient and enhanced blood pool CT imaging with imaging time up to 75 min. Likewise, thanks to the enhanced permeability and retention effect, the PEGylated Au PENPs were also able to be used as a contrast agent for effective CT imaging of a tumor model. With the proven organ biocompatibility by histological studies, the designed PEGylated Au PENPs may hold great promise to be used as contrast agents for CT imaging of a variety of biological systems. The significance of this study is that rather than the use of dendrimers as templates, cost-effective branched polymers (e.g., PEI) can be used as templates to generate functionalized AuNPs for CT imaging applications. PMID:25208617

  14. 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

  15. Portal vein aneurysm demonstrated by blood pool SPECT.

    PubMed

    Fukui, H; Kashiwagi, T; Kimura, K; Goto, M; Takei, Y; Kasahara, A; Kawano, S; Fusamoto, H; Kozuka, T; Kamada, T

    1992-11-01

    Portal vein aneurysms are rare and are occasionally suggested by ultrasound and usually confirmed by invasive angiography. Such a case was diagnosed by scintigraphic studies, most importantly blood pool SPECT, which clearly separates it from hepatic cysts. PMID:1424375

  16. 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

  17. Development and application of a multimodal contrast agent for SPECT/CT hybrid imaging.

    PubMed

    Criscione, Jason M; Dobrucki, Lawrence W; Zhuang, Zhen W; Papademetris, Xenophon; Simons, Michael; Sinusas, Albert J; Fahmy, Tarek M

    2011-09-21

    Hybrid or multimodality imaging is often applied in order to take advantage of the unique and complementary strengths of individual imaging modalities. This hybrid noninvasive imaging approach can provide critical information about anatomical structure in combination with physiological function or targeted molecular signals. While recent advances in software image fusion techniques and hybrid imaging systems have enabled efficient multimodal imaging, accessing the full potential of this technique requires development of a new toolbox of multimodal contrast agents that enhance the imaging process. Toward that goal, we report the development of a hybrid probe for both single photon emission computed tomography (SPECT) and X-ray computed tomography (CT) imaging that facilitates high-sensitivity SPECT and high spatial resolution CT imaging. In this work, we report the synthesis and evaluation of a novel intravascular, multimodal dendrimer-based contrast agent for use in preclinical SPECT/CT hybrid imaging systems. This multimodal agent offers a long intravascular residence time (t(1/2) = 43 min) and sufficient contrast-to-noise for effective serial intravascular and blood pool imaging with both SPECT and CT. The colocalization of the dendritic nuclear and X-ray contrasts offers the potential to facilitate image analysis and quantification by enabling correction for SPECT attenuation and partial volume errors at specified times with the higher resolution anatomic information provided by the circulating CT contrast. This may allow absolute quantification of intramyocardial blood volume and blood flow and may enable the ability to visualize active molecular targeting following clearance from the blood. PMID:21851119

  18. Nanoparticle encapsulation in red blood cells enables blood-pool magnetic particle imaging hours after injection

    NASA Astrophysics Data System (ADS)

    Rahmer, J.; Antonelli, A.; Sfara, C.; Tiemann, B.; Gleich, B.; Magnani, M.; Weizenecker, J.; Borgert, J.

    2013-06-01

    Magnetic particle imaging (MPI) is a new medical imaging approach that is based on the nonlinear magnetization response of super-paramagnetic iron oxide nanoparticles (SPIOs) injected into the blood stream. To date, real-time MPI of the bolus passage of an approved MRI SPIO contrast agent injected into the tail vein of living mice has been demonstrated. However, nanoparticles are rapidly removed from the blood stream by the mononuclear phagocyte system. Therefore, imaging applications for long-term monitoring require the repeated administration of bolus injections, which complicates quantitative comparisons due to the temporal variations in concentration. Encapsulation of SPIOs into red blood cells (RBCs) has been suggested to increase the blood circulation time of nanoparticles. This work presents first evidence that SPIO-loaded RBCs can be imaged in the blood pool of mice several hours after injection using MPI. This finding is supported by magnetic particle spectroscopy performed to quantify the iron concentration in blood samples extracted from the mice 3 and 24 h after injection of SPIO-loaded RBCs. Based on these results, new MPI applications can be envisioned, such as permanent 3D real-time visualization of the vessel tree during interventional procedures, bleeding monitoring after stroke, or long-term monitoring and treatment control of cardiovascular diseases.

  19. 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

  20. 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

  1. 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.

  2. Magnetic red blood cells as new contrast agents for MRI applications

    NASA Astrophysics Data System (ADS)

    Antonelli, Antonella; Sfara, Carla; Manuali, Elisabetta; Salamida, Sonia; Louin, Gaëlle; Magnani, Mauro

    2013-03-01

    Superparamagnetic iron oxide (SPIO) nanoparticles have been produced and used successfully as potent contrast agents for Magnetic Resonance Imaging (MRI). However, a significant challenge associated with the biological application of SPIO-tracer agents is their behavior in vivo since their efficacy is often compromised due to a rapid recognition and clearance by the reticuloendothelial system (RES) which limits the applicability of such compounds in MRI. The advances in nanotechnology and molecular cell biology had lead to improve stability and biocompatibility of these nanoparticles, but despite a number of efforts, the SPIO half-life in blood circulation is very short. In this contest, the potential of red blood cells (RBCs) loaded with SPIO nanoparticles as a tracer material for MRI has been investigated in order to realize a blood pool tracer with longer blood retention time. Previously, we have proposed the encapsulation into RBCs of superparamagnetic iron oxide nanoparticles carboxydextran coated, such as Resovist contrast agent. This approach led to a nanoparticle reduction in uptake by the RES, increasing the blood circulation half-life of nanoparticles. Recently, the loading procedure was applied to a new contrast agent, the P904 ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles coated by hydrophilic derivatives of glucose, recently developed by Guerbet Laboratories. The results evidenced that this nanomaterial can be efficiently loaded into human and murine RBCs at concentrations ranging from 1.5 to 12 mM Fe. In vivo experiments performed in mice have showed an increased survival in the mouse vascular system of P904 encapsulated into RBCs respect to free P904 sample intravenously injected at the equivalent amounts.

  3. 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

  4. 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.

  5. 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

  6. 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

  7. Crimson Carrier, A Long-Acting Contrast Agent for In Vivo Near-Infrared Imaging of Injured and Diseased Muscle

    PubMed Central

    Prajapati, Suresh I.; Martinez, Carlo O.; Abraham, Jinu; McCleish, Amanda T.; Michalek, Joel E.; McManus, Linda M.; Rubin, Brian P.; Shireman, Paula K.; Keller, Charles

    2010-01-01

    Introduction The near-infrared wavelengths (700nm–900nm) are the most suitable optical window for light penetration and deep tissue imaging in small animals. Herein we report a near-infrared fluorescent contrast agent, crimson carrier, which acts as a blood pool contrast agent to detect and quantify injury and disease in live animals. Methods After determining the excitation-emission spectra and pharmacokinetics, crimson carrier was injected into myoinjured mice to monitor their recovery. Crimson carrier was also used to image transgenic mice with spontaneous tumors. Results Crimson carrier has maximal excitation and emission wavelengths of 745 nm and 820 nm, respectively. Elimination occurs predominantly via urinary excretion. Discussion We demonstrate the utility of this contrast agent for serial imaging of traumatized muscle as well as muscle tumors. The unique long-acting pharmacokinetics and urinary excretion route characteristics make crimson carrier a contrast agent of choice for the visualization of tumors and injured muscle or other tissues in live animal studies. PMID:20544935

  8. 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.

  9. 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.

  10. Cinematic three-dimensional surface display of cardiac blood pool tomography

    SciTech Connect

    Honda, N.; Machida, K.; Takishima, T.; Mamiya, T.; Takahashi, T.; Kamano, T.; Tamaki, S.; Ban, R. )

    1991-02-01

    A method of three-dimensional cinematic display (3D cine) of cardiac blood pool tomography is described. ECG-gated transaxial blood pool imaging was obtained from a set of projection images that were collected from 32 images with 10 ECG-gated images per projection during a 180 degrees arc of a rotating gamma camera. A surface contour of the blood pool was determined by a set of isocount lines (40-55% of the maximum pixel counts) of the transaxial images. 3D cine was made by a depth-shading method, in which brightness of a given point on the contour was set proportional to the distance between the viewing plane and the point and to the incident angle formed by the viewing line and the surface of the point. In 15 patients, 3D cine showed hypokinesia, akinesia, dyskinesia, ventricular aneurysm, and opposite motions of the atria and ventricles. Diagnoses of left ventricular motion by 3D cine agreed well with those by echocardiography and contrast left ventriculography.

  11. Detection of varicocele by radionuclide blood-pool scanning

    SciTech Connect

    Freund, J.; Handelsman, D.J.; Bautovich, G.J.; Conway, A.J.; Morris, J.G.

    1980-10-01

    Varicocele is a common and treatable cause of male subfertility. The authors describe a new technique for varicocele detection using radionuclide blood-pool imaging of the scrotum. The results indicate that this technique detects unilateral varicoceles with high sensitivity, including some which are subclinical. There may be significant implications for treatment of infertility.

  12. 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.

  13. Slower Lower Limb Blood Pooling Increases Orthostatic Tolerance in Women with Vasovagal Syncope

    PubMed Central

    Skoog, Johan; Zachrisson, Helene; Länne, Toste; Lindenberger, Marcus

    2016-01-01

    Background and Aim: Slower lower limb blood pooling and associated blunted sympathetic activation has been detected in healthy women prone to orthostatic syncope. Whether these findings are true also for patients with vasovagal syncope (VVS) is unknown. The aim was to investigate initial blood pooling time (poolingtime, time to 50% of total blood pooling) together with hemodynamic responses and orthostatic tolerance during lower body negative pressure (LBNP) in VVS and healthy controls. Methods and Results: Fourteen VVS women (25.7 ± 1.3 years) and 15 healthy women (22.8 ± 0.8 years) were subjected to single-step and graded LBNP to pre-syncope. Lower limb blood pooling (ml · 100 ml−1), poolingtime (s), hemodynamic responses and LBNP-tolerance were evaluated. LBNP induced comparable lower limb blood pooling in both groups (controls, 3.1 ± 0.3; VVS, 2.9 ± 0.3 ml · 100 ml−1, P = 0.70). In controls, shorter poolingtime correlated to higher LBNP-tolerance (r = –0.550, P < 0.05) as well as better maintained stroke volume (r = –0.698, P < 0.01) and cardiac output (r = –0.563, P < 0.05). In contrast, shorter poolingtime correlated to lower LBNP-tolerance in VVS (r = 0.821, P < 0.001) and larger decline in stroke volume (r = 0.611, P < 0.05). Furthermore, in controls, shorter poolingtime correlated to baroreflex-mediated hemodynamic changes during LBNP, e.g., increased vasoconstriction (P < 0.001). In VVS, poolingtime was not correlated with LBNP-induced baroreceptor unloading, but rather highly correlated to resting calf blood flow (P < 0.001). Conclusions: Shorter poolingtime seems to elicit greater sympathetic activation with a concomitant higher orthostatic tolerance in healthy women. The contrasting findings in VVS indicate a deteriorated vascular sympathetic control suggesting well-defined differences already in the initial responses during orthostatic stress. PMID:27378941

  14. X-ray computed tomography contrast agents prepared by seeded growth of gold nanoparticles in PEGylated dendrimer

    NASA Astrophysics Data System (ADS)

    Kojima, Chie; Umeda, Yasuhito; Ogawa, Mikako; Harada, Atsushi; Magata, Yasuhiro; Kono, Kenji

    2010-06-01

    Gold nanoparticles (Au NPs) are a potential x-ray computed tomography (CT) contrast agent. A biocompatible and bioinactive surface is necessary for application of gold nanoparticle to CT imaging. Polyethylene glycol (PEG)-attached dendrimers have been used as a drug carrier with long blood circulation. In this study, the Au NPs were grown in the PEGylated dendrimer to produce a CT contrast agent. The Au NPs were grown by adding gold ions and ascorbic acid at various equivalents to the Au NP-encapsulated dendrimer solution. Both size and surface plasmon absorption of the grown Au NPs increased with adding a large number of gold ions. The x-ray attenuation of the Au NPs also increased after the seeded growth. The Au NPs grown in the PEG-attached dendrimer at the maximum under our conditions exhibited a similar CT value to a commercial iodine agent, iopamidol, in vitro. The Au NP-loaded PEGylated dendrimer and iopamidol were injected into mice and CT images were obtained at different times. The Au NP-loaded PEGylated dendrimer achieved a blood pool imaging, which was greater than a commercial iodine agent. Even though iopamidol was excreted rapidly, the PEGylated dendrimer loading the grown Au NP was accumulated in the liver.

  15. Dynamic circular buffering: a technique for equilibrium gated blood pool imaging.

    PubMed

    Vaquero, J J; Rahms, H; Green, M V; Del Pozo, F

    1996-03-01

    We have devised a software technique called "dynamic circular buffering" (DCB) with which we create a gated blood pool image sequence of the heart in real time using the best features of LIST and FRAME mode methods of acquisition/processing. The routine is based on the concept of independent "agents" acting on the timing and position data continuously written into the DCB. This approach allows efficient asynchronous operation on PC-type machines and enhanced capability on systems capable of true multiprocessing and multithreading. PMID:8904285

  16. [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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. Three dimensional quantification of left ventricular wall motion by ECG-gated blood pool emission tomography

    SciTech Connect

    Underwood, S.R.; Walton, S.; Laming, P.J.; Jarritt, P.H.; Ell, P.J.; Emanuel, R.W.; Swanton, R.H.

    1985-05-01

    ECG-gated blood pool emission tomography is a relatively new technique, and this study establishes a simple method for displaying the three dimensional data obtained, determines a normal range for ejection fraction in all regions of the left ventricle, and compares wall motion in abnormal subjects with that determined by X-ray contrast ventriculography. The short axis sections dividing the ventricle in slices from apex to base, were used to calculate ejection fraction for all parts of the ventricle and the results were plotted on a single colour coded circular image. The apex was represented in the centre, the base around the circumference, and all other parts of the ventricle were represented in between. The image was divided into 15 segments, and normal segmental ejection fraction was defined as within two standard deviations of the mean in a group of 10 normal subjects. In 25 subjects with coronary artery disease, motion of the anterior, apical, and inferior walls agreed in every case with the right anterior oblique contrast ventriculogram, but in 12 of these, the three dimensional ejection fraction image showed abnormal septal motion, and in a further 3, abnormal lateral wall motion in addition. In the 12 subjects there was disease of the left anterior descending coronary artery, and in the further 3 there was left circumflex disease. ECG-gated blood pool emission tomography thus provides an accurate quantitative assessment of left ventricular wall motion in three dimensions, and has significant advantages over conventional planar techniques.

  3. High-resolution three-dimensional scanning optical image system for intrinsic and extrinsic contrast agents in tissue

    NASA Astrophysics Data System (ADS)

    Gu, Yueqing; Qian, Zhiyu; Chen, Jinxian; Blessington, Dana; Ramanujam, Nimmi; Chance, Britton

    2002-01-01

    This article presents the theory and development of a three-dimensional (3D) imaging instrument capable of determining the biochemical properties of tissue by measuring the absorption or fluorescence of different intrinsic and extrinsic agents simultaneously. A bifurcated optical fiber bundle, serving to deliver the excitation light and collect the emission or reflection light, scans over the flat tissue surface retrieving optical signals in each pixel. Two-dimensional (2D) images of a series of subsequent sections are obtained after signal conversion and processing to yield a 3D image. Manipulation of the scanning step and diameter size of the fibers within the bundle, the spatial resolution of the instrument attains a maximum of 40 × 40 × 10 μm3. The wavelength range is extended from ultraviolet to the near infrared (NIR) through specialized optical design, typically employed for the NIR extrinsic contrast agents study. The instrument is most applicable in situations involving the measurement of fluorescence or absorption at any specific wavelength within the spectrum range. Flavoprotein and nicotinamide adeine dinucleotide are the two typical intrinsic agents indicating the oxidization and reduction status of the tissue sample, with their fluorescence detected at wavelengths of 540 and 440 nm, respectively. Oxy and deoxy hemoglobin are two other significant intrinsic agents for evaluating the blood oxygenation saturation by recording their absorptions at two different wavelengths of 577 and 546 nm. These intrinsic agents were measured in this study for comparison of biochemical properties of rat liver in different gas inhalation treatments. Indocyanine green, a NIR extrinsic contrast agent measured at wavelengths of 780 nm/830 nm as excitation/emission can indicate blood pooling by displaying the distribution of blood vessels within a 9 L tumor. The advantage of high sensitivity, spatial resolution, and broad applied potentiality were demonstrated by the

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. ECG-gated blood pool tomography in the determination of left ventricular volume, ejection fraction, and wall motion

    SciTech Connect

    Underwood, S.R.; Ell, P.J.; Jarritt, P.H.; Emanuel, R.W.; Swanton, R.H.

    1984-01-01

    ECG-gated blood pool tomography promises to provide a ''gold standard'' for noninvasive measurement of left ventricular volume, ejection fraction, and wall motion. This study compares these measurements with those from planar radionuclide imaging and contrast ventriculography. End diastolic and end systolic blood pool images were acquired tomographically using an IGE400A rotating gamma camera and Star computer, and slices were reconstructed orthogonal to the long axis of the heart. Left ventricular volume was determined by summing the areas of the slices, and wall motion was determined by comparison of end diastolic and end systolic contours. In phantom experiments this provided an accurate measurement of volume (r=0.98). In 32 subjects who were either normal or who had coronary artery disease left ventricular volume (r=0.83) and ejection fraction (r=0.89) correlated well with those using a counts based planar technique. In 16 of 18 subjects who underwent right anterior oblique X-ray contrast ventriculography, tomographic wall motion agreed for anterior, apical, and inferior walls, but abnormal septal motion which was not apparent by contrast ventriculography, was seen in 12 subjects tomographically. All 12 had disease of the left anterior descending coronary artery and might have been expected to have abnormal septal motion. ECG-gated blood pool tomography can thus determine left ventricular volume and ejection fraction accurately, and provides a global description of wall motion in a way that is not possible from any single planar image.

  10. 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

  11. 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

  12. 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

  13. 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.

  14. 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.

  15. 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

  16. Synthesis of Fluorine-18 Radio-labeled Serum Albumins for PET Blood Pool Imaging

    PubMed Central

    Basuli, Falguni; Li, Changhui; Xu, Biying; Williams, Mark; Wong, Karen; Coble, Vincent L; Vasalatiy, Olga; Seidel, Jurgen; Green, Michael V.; Griffiths, Gary L.; Choyke, Peter L.; Jagoda, Elaine M.

    2015-01-01

    We sought to develop a practical, reproducible and clinically translatable method of radiolabeling serum albumins with fluorine-18 for use as a PET blood pool imaging agent in animals and man. Fluorine-18 radiolabeled fluoronicotinic acid-2,3,5,6-tetrafluorophenyl ester, [18F]F-Py-TFP was prepared first by the reaction of its quaternary ammonium triflate precursor with [18F]tetrabutylammonium fluoride ([18F]TBAF) according to a previously published method for peptides, with minor modifications. The incubation of [18F]F-Py-TFP with rat serum albumin (RSA) in phosphate buffer (pH 9) for 15 min at 37–40 °C produced fluorine-18-radiolabeled RSA and the product was purified using a mini-PD MiniTrap G-25 column. The overall radiochemical yield of the reaction was 18–35% (n = 30, uncorrected) in a 90-min synthesis. This procedure, repeated with human serum albumin (HSA), yielded similar results. Fluorine-18-radiolabeled RSA demonstrated prolonged blood retention (biological half-life of 4.8 hours) in healthy awake rats. The distribution of major organ radioactivity remained relatively unchanged during the 4 hour observation periods either by direct tissue counting or by dynamic PET whole-body imaging except for a gradual accumulation of labeled metabolic products in the bladder. This manual method for synthesizing radiolabeled serum albumins uses fluorine-18, a widely available PET radionuclide, and natural protein available in both pure and recombinant forms which could be scaled up for widespread clinical applications. These preclinical biodistribution and PET imaging results indicate that [18F]RSA is an effective blood pool imaging agent in rats and might, as [18F]HSA, prove similarly useful as a clinical imaging agent. PMID:25533724

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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).

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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.

  1. PEGylated dendrimer-entrapped gold nanoparticles for in vivo blood pool and tumor imaging by computed tomography.

    PubMed

    Peng, Chen; Zheng, Linfeng; Chen, Qian; Shen, Mingwu; Guo, Rui; Wang, Han; Cao, Xueyan; Zhang, Guixiang; Shi, Xiangyang

    2012-02-01

    We report the synthesis and characterization of dendrimer-entrapped gold nanoparticles (Au DENPs) modified by polyethylene glycol (PEG) with enhanced biocompatibility for computed tomography (CT) imaging applications. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5.NH(2)) modified by PEG monomethyl ether (G5.NH(2)-mPEG(20)) were used as templates to synthesize Au DENPs, followed by acetylation of the remaining dendrimer terminal amines to generate PEGylated Au DENPs. The partial PEGylation modification of dendrimer terminal amines allows high loading of Au within the dendrimer interior, and consequently by simply varying the Au salt/dendrimer molar ratio, the size of the PEGylated Au DENPs can be controlled at a range of 2-4 nm with a narrow size distribution. The formed PEGylated Au DENPs are water-dispersible, stable in a pH range of 5-8 and a temperature range of 0-50 °C, and non-cytotoxic at a concentration as high as 100 μm. X-ray absorption coefficient measurements show that the attenuation intensity of the PEGylated Au DENPs is much higher than that of Omnipaque with iodine concentration similar to Au. With the sufficiently long half-decay time demonstrated by pharmacokinetics studies, the PEGylated Au DENPs enabled not only X-ray CT blood pool imaging of mice and rats after intravenous injection of the particles, but also effective CT imaging of a xenograft tumor model in nude mice. These findings suggest that the designed PEGylated Au DENPs can be used as a promising contrast agent with enhanced biocompatibility for CT imaging of various biological systems, especially in cancer diagnosis. PMID:22061490

  2. 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.

  3. 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

  4. 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.

  5. 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

  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. Non-invasive detection of macrophages in atheroma using a radiocontrast-loaded phosphatidylserine-containing liposomal contrast agent for computed tomography

    PubMed Central

    Kee, Patrick; Bagalkot, Vaishali; Johnson, Evan; Danila, Delia

    2014-01-01

    Purpose Macrophage plays an important role in plaque destabilization in atherosclerosis. By harnessing the affinity of macrophages to certain phospholipid species, a liposomal contrast agent containing phosphatidylserine (PS) and computed tomographic (CT) contrast agent was prepared and evaluated for CT imaging of plaque-associated macrophages in rabbit models of atherosclerosis. Procedures Liposomes containing PS and iodixanol were evaluated for their physicochemical characteristics, in vitro macrophage uptake, in vivo blood pool clearance and organ distribution. Plaque enhancement in the aorta was imaged with computed tomography (CT) in two atherosclerotic rabbit models. Results In vitro macrophage uptake of PS-liposomes increased with increasing amount of PS in the liposomes. Overall clearance of PS-liposomes was more rapid than control liposomes. Smaller PS-liposomes (d = 112 ± 4 nm) were more effective than control liposomes of similar size or larger control and PS-liposomes (d = 172 ± 17 nm) in enhancing aortic plaques in both rabbit models. Conclusions Proper liposomal surface modification and appropriate sizing are important determinant for CT-based molecular imaging of macrophages in atheroma. PMID:25301703

  15. 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

  16. 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

  17. 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

  18. 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.

  19. Towards An Advanced Graphene-Based Magnetic Resonance Imaging Contrast Agent: Sub-acute Toxicity and Efficacy Studies in Small Animals

    PubMed Central

    Kanakia, Shruti; Toussaint, Jimmy; Hoang, Dung Minh; Mullick Chowdhury, Sayan; Lee, Stephen; Shroyer, Kenneth R.; Moore, William; Wadghiri, Youssef Z.; Sitharaman, Balaji

    2015-01-01

    Current clinical Gd3+-based T1 magnetic resonance imaging (MRI) contrast agents (CAs) are suboptimal or unsuitable, especially at higher magnetic fields (>1.5 Tesla) for advanced MRI applications such as blood pool, cellular and molecular imaging. Herein, towards the goal of developing a safe and more efficacious high field T1 MRI CA for these applications, we report the sub-acute toxicity and contrast enhancing capabilities of a novel nanoparticle MRI CA comprising of manganese (Mn2+) intercalated graphene nanoparticles functionalized with dextran (hereafter, Mangradex) in rodents. Sub-acute toxicology performed on rats intravenously injected with Mangradex at 1, 50 or 100 mg/kg dosages 3 times per week for three weeks indicated that dosages ≤50 mg/kg could serve as potential diagnostic doses. Whole body 7 Tesla MRI performed on mice injected with Mangradex at a potential diagnostic dose (25 mg/kg or 455 nanomoles Mn2+/kg; ~2 orders of magnitude lower than the paramagnetic ion concentration in a typical clinical dose) showed persistent (up to at least 2 hours) contrast enhancement in the vascular branches (Mn2+ concentration in blood at steady state = 300 ppb, per voxel = 45 femtomoles). The results lay the foundations for further development of Mangradex as a vascular and cellular/ molecular MRI probe. PMID:26625867

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. 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

  8. Cardiac blood-pool scintigraphy in rats and hamsters: comparison of five radiopharmaceuticals and three pinhole collimator apertures

    SciTech Connect

    Pieri, P.; Fischman, A.J.; Ahmad, M.; Moore, R.H.; Callahan, R.J.; Strauss, H.W. )

    1991-05-01

    Preclinical evaluation of cardiac drugs may require evaluation of cardiac function in intact animals. To optimize the quality of radionuclide measurements of ventricular function in small animals, a comparison was made of gated blood-pool scans recorded with five blood-pool radiopharmaceuticals ({sup 99}mTc-labeled human polyclonal IgG, {sup 99}mTc-human serum albumin labeled by two methods, and red blood cells radiolabeled with {sup 99}mTc via in vivo and in vitro methods) in rats and three pinhole apertures in hamsters. The quality of the radiopharmaceuticals was evaluated by comparing count density ratios (LV/BACKGROUND and LV/LIVER) and ejection fractions recorded with each agent. The edge definition of the left ventricle and count rate performance of the 1-, 2-, and 3-mm apertures was evaluated in hamsters. In general, the images obtained with the radiolabeled cells were superior to those obtained with the labeled proteins and no significant differences between the protein preparations were detected. Left ventricular ejection fractions calculated with all five radiopharmaceuticals were not significantly different. The best quality images were obtained with the 1-mm pinhole collimator. Ejection fraction and acquisition time were inversely related to aperture size. A good compromise between resolution and sensitivity was obtained with the 2-mm pinhole collimator.

  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. Multi-modal magnetic resonance imaging and histology of vascular function in xenografts using macromolecular contrast agent hyperbranched polyglycerol (HPG-GdF).

    PubMed

    Baker, Jennifer H E; McPhee, Kelly C; Moosvi, Firas; Saatchi, Katayoun; Häfeli, Urs O; Minchinton, Andrew I; Reinsberg, Stefan A

    2016-01-01

    Macromolecular gadolinium (Gd)-based contrast agents are in development as blood pool markers for MRI. HPG-GdF is a 583 kDa hyperbranched polyglycerol doubly tagged with Gd and Alexa 647 nm dye, making it both MR and histologically visible. In this study we examined the location of HPG-GdF in whole-tumor xenograft sections matched to in vivo DCE-MR images of both HPG-GdF and Gadovist. Despite its large size, we have shown that HPG-GdF extravasates from some tumor vessels and accumulates over time, but does not distribute beyond a few cell diameters from vessels. Fractional plasma volume (fPV) and apparent permeability-surface area product (aPS) parameters were derived from the MR concentration-time curves of HPG-GdF. Non-viable necrotic tumor tissue was excluded from the analysis by applying a novel bolus arrival time (BAT) algorithm to all voxels. aPS derived from HPG-GdF was the only MR parameter to identify a difference in vascular function between HCT116 and HT29 colorectal tumors. This study is the first to relate low and high molecular weight contrast agents with matched whole-tumor histological sections. These detailed comparisons identified tumor regions that appear distinct from each other using the HPG-GdF biomarkers related to perfusion and vessel leakiness, while Gadovist-imaged parameter measures in the same regions were unable to detect variation in vascular function. We have established HPG-GdF as a biocompatible multi-modal high molecular weight contrast agent with application for examining vascular function in both MR and histological modalities. PMID:26268906

  13. 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

  14. Ultrasound Contrast Materials in Cardiovascular Medicine: from Perfusion Assessment to Molecular Imaging

    PubMed Central

    Klibanov, Alexander L

    2013-01-01

    Ultrasound imaging is widely used in cardiovascular diagnostics. Contrast agents expand the range of tasks that ultrasound can perform. In the clinic in US, endocardial border delineation and left ventricle opacification have been an approved indication for more than a decade. However, myocardial perfusion contrast ultrasound studies are still at the clinical trials stage. Blood pool contrast and perfusion in other tissues might be an easier indication to achieve: general blood pool ultrasound contrast is in wider use in Europe, Canada, Japan, and China. Targeted (molecular) contrast microbubbles will be the next generation of ultrasound imaging probes, capable of specific delineation of the areas of disease by adherence to molecular targets. The shell of targeted microbubbles (currently in the preclinical research and early stage clinical trials) is decorated with the ligands (antibodies, peptides or mimetics, hormones, carbohydrates) that ensure firm binding to the molecular markers of disease. PMID:23913363

  15. Assessment of the site of ventricular activation by Fourier analysis of gated blood-pool studies

    SciTech Connect

    Links, J.M.; Raichlen, J.S.; Wagner, H.N. Jr.; Reid, P.R.

    1985-01-01

    The authors studied the use of first-harmonic Fourier analysis of gated blood-pool images to assess the site of ventricular activation in a group of 12 patients undergoing electrophysiologic pacing studies. They acquired gated blood-pool studies during pacing at up to four sites at each of two different rates. A total of 50 studies were made. At a pacing rate of 100 beats/min, when the pacing electrode was the right-ventricular outflow tract, 7/8; at the anterolateral left-ventricular wall, 4/4. When the Fourier activation site was at the right-ventricular apex, 9/9 times the pacing electrode was there; at the right-ventricular outflow tract, 7/10; in the left ventricle, 4/4. Fourier analysis of gated blood-pool studies can help identify the site of ventricular activation but is not sufficiently accurate to fully replace endocardial mapping.

  16. 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

  17. ECG-gated emission computed tomography of the cardiac blood pool

    SciTech Connect

    Moore, M.L.; Murphy, P.H.; Burdine, J.A.

    1980-01-01

    ECG-gated cross-sectional images of the cardiac blood pool were produced using a specially constructed emission computed tomographic scanner. A pair of large-field-of-view cameras were mounted in opposition in a gantry that rotates 360/sup 0/ about the patient. The coordinates of each detected event, the output of a physiological synchronizer, and the position of the camera heads were input to a dedicated minicomputer which was used to produce the images. Display as a movie permitted evaluation of regional and global wall motion in cross section without the disadvantages of superimposed blood pools as obtained in nontomographic views.

  18. 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

  19. [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

  20. 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

  1. 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

  2. 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.

  3. 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

  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. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. Use of blood-pool imaging in evaluation of diffuse activity patterns in technetium-99m pyrophosphate myocardial scintigraphy.

    PubMed

    Cowley, M J; Mantle, J A; Rogers, W J; Russell, R O; Rackley, C E; Logic, J R

    1979-06-01

    It has been suggested that diffuse Tc-99m pyrophosphate precordial activity may be due to persistent blood-pool activity in routine delayed views during myocardial imaging. To answer this question, we reviewed myocardial scintigrams recorded 60--90 min following the injection of 12--15 mCi of Tc-99m pyrophosphate for the presence of diffuse precordial activity, and compared these with early images of the blood pool in 265 patients. Diffuse activity in the delayed images was identified in 48 patients: in 20 with acute myocardial infarction and in 28 with no evidence of it. Comparison of these routine delayed images with early views of the blood pool revealed two types of patterns. In patients with acute infarction, 95% had delayed images that were distinguishable from blood pool either because the activity was smaller than the early blood pool, or by the presence of localized activity superimposed on diffuse activity identical to blood pool. In those without infarction, 93% had activity distribution in routine delayed views matching that in the early blood-pool images. The usefulness of the diffuse TcPPi precordial activity in myocardial infarction is improved when early blood-pool imaging is used to exclude persistence of blood-pool activity as its cause. Moreover, it does not require additional amounts of radioactivity nor complex computer processing, a feature that may be of value in the community hospital using the technique to "rule out" infarction 24--72 hr after onset of suggestive symptoms. PMID:231644

  12. 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

  13. Design of an automated algorithm for labeling cardiac blood pool in gated SPECT images of radiolabeled red blood cells

    SciTech Connect

    Hebert, T.J. |; Moore, W.H.; Dhekne, R.D.; Ford, P.V.; Wendt, J.A.; Murphy, P.H.; Ting, Y.

    1996-08-01

    The design of an automated computer algorithm for labeling the cardiac blood pool within gated 3-D reconstructions of the radiolabeled red blood cells is investigated. Due to patient functional abnormalities, limited resolution, and noise, certain spatial and temporal features of the cardiac blood pool that one would anticipate finding in every study are not present in certain frames or with certain patients. The labeling of the cardiac blood pool requires an algorithm that only relies upon features present in all patients. The authors investigate the design of a fully-automated region growing algorithm for this purpose.

  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. 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

  18. Recent Experiences and Advances in Contrast-Enhanced Subharmonic Ultrasound

    PubMed Central

    Eisenbrey, John R.; Liu, Ji-Bin; Forsberg, Flemming

    2015-01-01

    Nonlinear contrast-enhanced ultrasound imaging schemes strive to suppress tissue signals in order to better visualize nonlinear signals from blood-pooling ultrasound contrast agents. Because tissue does not generate a subharmonic response (i.e., signal at half the transmit frequency), subharmonic imaging has been proposed as a method for isolating ultrasound microbubble signals while suppressing surrounding tissue signals. In this paper, we summarize recent advances in the use of subharmonic imaging in vivo. These advances include the implementation of subharmonic imaging on linear and curvilinear arrays, intravascular probes, and three-dimensional probes for breast, renal, liver, plaque, and tumor imaging. PMID:26090430

  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. 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.

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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.

  13. Adaptive volume rendering of cardiac 3D ultrasound images: utilizing blood pool statistics

    NASA Astrophysics Data System (ADS)

    Åsen, Jon Petter; Steen, Erik; Kiss, Gabriel; Thorstensen, Anders; Rabben, Stein Inge

    2012-03-01

    In this paper we introduce and investigate an adaptive direct volume rendering (DVR) method for real-time visualization of cardiac 3D ultrasound. DVR is commonly used in cardiac ultrasound to visualize interfaces between tissue and blood. However, this is particularly challenging with ultrasound images due to variability of the signal within tissue as well as variability of noise signal within the blood pool. Standard DVR involves a global mapping of sample values to opacity by an opacity transfer function (OTF). While a global OTF may represent the interface correctly in one part of the image, it may result in tissue dropouts, or even artificial interfaces within the blood pool in other parts of the image. In order to increase correctness of the rendered image, the presented method utilizes blood pool statistics to do regional adjustments of the OTF. The regional adaptive OTF was compared with a global OTF in a dataset of apical recordings from 18 subjects. For each recording, three renderings from standard views (apical 4-chamber (A4C), inverted A4C (IA4C) and mitral valve (MV)) were generated for both methods, and each rendering was tuned to the best visual appearance by a physician echocardiographer. For each rendering we measured the mean absolute error (MAE) between the rendering depth buffer and a validated left ventricular segmentation. The difference d in MAE between the global and regional method was calculated and t-test results are reported with significant improvements for the regional adaptive method (dA4C = 1.5 +/- 0.3 mm, dIA4C = 2.5 +/- 0.4 mm, dMV = 1.7 +/- 0.2 mm, d.f. = 17, all p < 0.001). This improvement by the regional adaptive method was confirmed through qualitative visual assessment by an experienced physician echocardiographer who concluded that the regional adaptive method produced rendered images with fewer tissue dropouts and less spurious structures inside the blood pool in the vast majority of the renderings. The algorithm has been

  14. Fourier analysis of a gated blood-pool study during atrial flutter

    SciTech Connect

    Makler, P.T. Jr.; McCarthy, D.M.; London, J.W.; Sandler, M.S.; Alavi, A.

    1983-08-01

    First-harmonic Fourier analysis of a gated blood-pool study is based on the assumption that the cardiac chambers contract once per cardiac cycle. In atrial arrhythmias this condition may not exist for the atria. We recently studied a patient with atrial flutter and 2:1 artioventricular conduction. There were predictable alterations in the first-harmonic Fourier phase and amplitude images. The observed changes from first-harmonic Fourier analysis were: (a) very low atrial amplitude values, and (b) absence of identifiable atrial regions on the phase image.

  15. 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).

  16. 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.

  17. 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

  18. [Left ventricular early diastolic filling and atrial contribution assessed by ECG-gated cardiac blood pool scintigraphy].

    PubMed

    Kondo, T; Hishida, H; Furuta, T; Sawano, T; Kurokawa, H; Kiriyama, T; Kato, Y; Watanabe, Y; Mizuno, Y; Takeuchi, A

    1986-01-01

    This study evaluated early diastolic left ventricular (LV) filling and the atrial contribution to ventricular filling in patients (pts) with various heart diseases using ECG-gated cardiac blood pool scintigraphy. Conventional equilibrium list mode ECG-gated cardiac blood pool scintigraphy was performed for 19 normal subjects (N) as controls, 104 pts with old myocardial infarction (OMI), 19 pts with essential hypertension (HT), seven pts with idiopathic hypertrophic subaortic stenosis (IHSS), three pts with non-obstructive hypertrophic cardiomyopathy (HCM), 19 pts with pure mitral stenosis (MS) and one pt with both MS and aortic regurgitation to evaluate early diastolic LV filling. The LV stroke counts corresponding to stroke volume and the early diastolic LV peak filling rate (DdV/dt) were obtained from the LV time-activity curve and its first derivative. Then the DdV/dt was normalized by stroke counts. The DdV/dt was significantly lower in pts with OMI (4.34 +/- 1.02/sec, p less than 0.001), HT (3.93 +/- 0.70/sec, p less than 0.001), IHSS (4.23 +/- 1.59/sec, p less than 0.01) and MS (4.56 +/- 1.05/sec, p less than 0.01) than in N (5.93 +/- 1.26/sec). Then, in OMI, the DdV/dt correlated significantly (r = -0.45, p less than 0.05) with infarct size (% abnormal contracting segment = %ACS) obtained by contrast left ventriculography. Furthermore, in pts with HT, the DdV/dt correlated significantly (r = -0.59, p less than 0.02) with the left ventricular mean wall thickness obtained by M-mode echocardiography. In pts with MS, the DdV/dt also correlated significantly (r = 0.73, p less than 0.001) with the mitral orifice area obtained by two-dimensional echocardiography. However, it has been difficult to assess the atrial contribution to ventricular filling by conventional ECG-gated cardiac blood pool scintigraphy, because the LV time-activity curve in the late diastolic phase was distorted and unreliable, whenever a minimal variation of the R-R interval occurred

  19. Blood Pool Segmentation Results in Superior Virtual Cardiac Models than Myocardial Segmentation for 3D Printing.

    PubMed

    Farooqi, Kanwal M; Lengua, Carlos Gonzalez; Weinberg, Alan D; Nielsen, James C; Sanz, Javier

    2016-08-01

    The method of cardiac magnetic resonance (CMR) three-dimensional (3D) image acquisition and post-processing which should be used to create optimal virtual models for 3D printing has not been studied systematically. Patients (n = 19) who had undergone CMR including both 3D balanced steady-state free precession (bSSFP) imaging and contrast-enhanced magnetic resonance angiography (MRA) were retrospectively identified. Post-processing for the creation of virtual 3D models involved using both myocardial (MS) and blood pool (BP) segmentation, resulting in four groups: Group 1-bSSFP/MS, Group 2-bSSFP/BP, Group 3-MRA/MS and Group 4-MRA/BP. The models created were assessed by two raters for overall quality (1-poor; 2-good; 3-excellent) and ability to identify predefined vessels (1-5: superior vena cava, inferior vena cava, main pulmonary artery, ascending aorta and at least one pulmonary vein). A total of 76 virtual models were created from 19 patient CMR datasets. The mean overall quality scores for Raters 1/2 were 1.63 ± 0.50/1.26 ± 0.45 for Group 1, 2.12 ± 0.50/2.26 ± 0.73 for Group 2, 1.74 ± 0.56/1.53 ± 0.61 for Group 3 and 2.26 ± 0.65/2.68 ± 0.48 for Group 4. The numbers of identified vessels for Raters 1/2 were 4.11 ± 1.32/4.05 ± 1.31 for Group 1, 4.90 ± 0.46/4.95 ± 0.23 for Group 2, 4.32 ± 1.00/4.47 ± 0.84 for Group 3 and 4.74 ± 0.56/4.63 ± 0.49 for Group 4. Models created using BP segmentation (Groups 2 and 4) received significantly higher ratings than those created using MS for both overall quality and number of vessels visualized (p < 0.05), regardless of the acquisition technique. There were no significant differences between Groups 1 and 3. The ratings for Raters 1 and 2 had good correlation for overall quality (ICC = 0.63) and excellent correlation for the total number of vessels visualized (ICC = 0.77). The intra-rater reliability was good for Rater A (ICC = 0.65). Three models were successfully printed

  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. 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.

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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.

  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. [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

  12. 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

  13. 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.

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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

  2. 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

  3. 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

  4. 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.

  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. Patterns of ventricular emptying by Fourier analysis of gated blood-pool studies

    SciTech Connect

    Links, J.M.; Douglass, K.H.; Wagner, H.N. Jr.

    1980-10-01

    Temporal Fourier analysis was applied to the processing of ECG-gated cardiac blood-pool studies on a pixel-by-pixel basis, to yield information about the pattern of ventricular emptying in normal hearts and in others with conduction abnormalities. The transform data at the fundamental frequency (the heart rate) were used to construct two types of display: (a) a distribution histogram of the pixel phase values, and (b) a cinematic display of the wave of emptying as it spread over the cardiac chambers. Preliminary results indicate that temporal Fourier analysis permits visualization of the pattern of ventricular emptying, which may prove useful in the study of motion abnormalities and asynergies, including those resulting from myocardial hypertrophy or conduction abnormalities, and as an aid in the optimum placement of pacemakers.

  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. 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.

  12. 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.

  13. 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

  14. 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.

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. 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.

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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